OncologyLive® is the flagship publication of OncLive®. Each issue delivers expert insights and clinical oncology news and updates, which impact the day-to-day clinical practice of oncology professionals who work tirelessly to help improve patient outcomes.

Emerging strategies leveraging biomarker data for the treatment of patients with early-stage and metastatic colorectal cancer (CRC) have made precision medicine a top-of-mind topic for gastrointestinal oncologists. “We have medicines that are very specific…increasing immunotherapy options, increasing precision medicine options; it’s a little more complicated than it was before,” 

discussion during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. In the discussion, a panel of leaders in GI oncology unpacked the latest developments in 

V600E–mutated disease as well as the use of circulating tumor DNA (ctDNA) and minimal residual disease (MRD) in the management of metastatic CRC in the first half of the program.

The panel had a specific focus on the available guidance and data concerning testing and implementing these strategies to guide decision-making in the clinic. “We are in a time where we have the benefit of having a lot of specific inhibitors, some [available] in standard practice, some on trial, but we really want to start and parcel off some of these rare molecular subgroups and give them therapies that probably work a lot better than our cytotoxins,” 

However, Cohen noted that the first step for any treatment decision is to consider all options and not jump right to targeted therapy. “It’s a fun time because you have so much leverage on what you do. You get to think about all the different options. You get to have a discussion with patients. But that’s also an uncomfortable space because there’s not one right way to do it. It comes down to guiding the discussion based on the information that you have, figuring out what other information you need, and then trying to move the plan forward. First, I’m thinking about a patient. If they [have] metastatic [disease], you’re going to have [to] pause and say: Is this someone who [has] widely metastatic [disease], or do we have the chance to think about this as oligometastatic [disease that is] potentially curable, potentially resectable, especially if it’s [metastatic to the] liver only? We’re going to be thinking about this in a multidisciplinary fashion, even in stage IV.”

For those patients with widely metastatic disease, Cohen said she would proceed to leveraging molecular markers to guide treatment. With turnaround times becoming an ever-present hurdle, Cohen noted that at the first meeting she sends liquid biopsy samples out on the day she meets with patients. “The first thing that we need to know is whether [a patient has] microsatellite instability [MSI], because we know that those patients should be on first-line immunotherapy. We’ve [started] recognizing that MSI-high [MSI-H] cancer is a different disease, and we need to flag that those patients absolutely need immunotherapy if it’s not contraindicated.”

Clinical guidelines state that all patients with CRC should undergo reflex testing for MSI-H or mismatch repair–deficient (dMMR) disease.

, HER2, [or] anything else that we think might be a driver mutation. And not just do they have one of those mutations, but what is the specific mutation?”

 mutations are mostly focused on the point mutation, 

V600E, which has presented a unique therapeutic opportunity to enhance clinical outcomes for patients. “When we mention 

, we’re really focused on the V600E mutation,” 

, said. “It’s involved in the RAS and MAPK pathways. We understand that it’s pretty rare, [appearing in] approximately less than 10% of our patient population, roughly 9%, but the fact is that it is a poor prognostic indicator for overall survival [OS] for our patients. The good news is that we have a drug that we can use for these patients.”

The BRAF V600E inhibitor encorafenib (Braftovi) is approved in combination with the EGFR inhibitor cetuximab (Erbitux) based on data from the phase 3 BEACON CRC trial (NCT02928224).

 Eng noted that encorafenib needs the support of cetuximab unlike other cancers where the agent has demonstrated efficacy as a single agent. Marshall concurred, adding, “[In CRC], you can have a perfectly good marker, you block it, and all [the disease] does is go around it. It’s sort of swampy; you block 1 river, but it just swamps its way around. In almost all [treatments for CRC], we need to hit these pathways more than once.”

Despite the success seen with encorafenib, it is only an option in the second-line setting, to which Marshall posed the question of what can be done in the first line. “Clinical trials. There are first-line clinical trials, and we’ve started to see some of those data combining with chemotherapy with 

-targeting therapy in the first-line [setting in CRC],” 

 to inform eligibility for trials is also vital. “We have other clinical trials that are focused on the 

 mutation, and doctors [should be] familiar and comfortable with ordering 

 testing. We encourage it because that information is extremely critical to making a decision about whether patients are going to go on a newly diagnosed, 

-mutant, metastatic [disease] trial or are going to just receive standard of care and proceed to [BRAF inhibitors] in the second-line setting.”

One of the ongoing studies in the first-line setting is the BREAKWATER trial (NCT04607421) evaluating the efficacy of the encorafenib/cetuximab combination in the first-line setting.

 “The reasoning for this is, as we learned from BEACON and as we’ve seen with the phase 2 ANCHOR-CRC [NCT03693170], that there’s a potential larger benefit as we move these agents to earlier lines of therapy,” 

, said. “It makes sense. You hit biology early, you’re going to have your best benefit.”

The study is enrolling patients with metastatic 

 V600E–mutant CRC who have received no prior therapy for metastatic disease and have measurable disease per RECIST 1.1 criteria. Prior treatment with a BRAF or EGFR inhibitor or known MSI-H/dMMR status is prohibited. Patients will be randomly assigned 1:1:1 to encorafenib plus cetuximab, encorafenib/cetuximab plus modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin), or modified FOLFOX6/FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan)/CAPOX (capecitabine and oxaliplatin) with or without bevacizumab (Avastin). The study will also include a separate cohort of patients who will be randomly assigned 2:1 to encorafenib/cetuximab/FOLFIRI (folinic acid, fluorouracil, and irinotecan) or FOLFIRI/bevacizumab.

Primary end points are progression-free survival and overall response rate (ORR) between the encorafenib/cetuximab/modified FOLFOX6 arm and the FOLFOX6/FOLFOXIRI/CAPOX with or without bevacizumab arm. The primary end point in the separate cohort is ORR.

“The first data that came out from BREAKWATER from the lead-in studies looked incredibly promising, with FOLFOX [looking a] little more promising with FOLFIRI. But the choice was to proceed with FOLFOX primarily based on pharmacokinetic parameters,” Bekaii-Saab said.

In terms of testing for trial enrollment, Bekaii-Saab and Cohen noted that improving outcomes requires fast turnaround of results to match patients with optimal care. For example, the BREAKWATER study requires 

V600E confirmation on either blood or tumor tissue testing.

 “One of the good aspects of this study, and one that’s actually a good lesson for drug development, is that the sponsor of the study has done a great job allowing us to act on liquid biopsies, given the high component rate,” Bekaii-Saab said. “In fact, the first 2 patients from my clinic who went on this study were found to have their 

 V600E mutations on liquid biopsy [results], which certainly have facilitated access. We have to move fast, especially in the United States. There’s no waiting.”

Cohen noted an experience in her clinic that has also changed her practice: “What prompted us to start doing liquid biopsy is that I had a patient whose results came back later on a tissue sample [positive for 

V600E], and I realized it was a missed opportunity. We want to always be offering these opportunities to patients, especially for those with poor prognostic disease.”

Although testing for mutations tackles one part of the diagnostic battle, tumor sidedness has also been cited as a means for determining. Data have demonstrated that outcomes with systemic treatment vary based on whether the tumor is located on the left or right side of the colon.

 For instance, the right side of the colon is associated with MSI-H disease and 

 mutations, and tumors from this side typically do not benefit from EGFR inhibitors. Left-sided tumors are more common and have demonstrated benefit with EGFR inhibitors.

However, at the 2023 ASCO Gastrointestinal Cancers Symposium, Shitara et al presented findings from the PARADIGM study (NCT02394795) on how ctDNA can aid in the guidance of hyperselection of patients for treatment rather than tumor sidedness. “We’ve learned over the years of the prognostic differences between the sidedness [and] started to understand the first-line differences of anti-EGFR therapy for the patients [with] right-sided [tumors],” Parikh said. “The dogma has moved toward approaches stating that patients [with] right-sided [tumors] don’t benefit from anti-EGFR therapy. But it’s more [complex] than that, and there is a subset of biomarkers present in selected patients.”

Investigators of PARADIGM looked at hyperselected patients, defined as those with alterations identified in ctDNA that confer resistance to EGFR, such as 

 “These are what you would think would portend resistance to anti-EGFR therapy,” Parikh said. “Even on the right-sided [tumors], if you don’t have those biomarkers that will predict lack of benefit, they’re patients who benefit. To have kept [decision-making] as simple as just [considering] sidedness is bad. It’s why I like liquid biopsy for patients.”

Parikh said that she would not select patients with right-sided tumors for EGFR inhibitors in the first-line setting but would consider it in later-line settings. “I think there might be biomarkers, such as ctDNA, that can help us figure out whom those patients are who may or may not benefit.”

Findings from PARADIGM showed that using ctDNA to hyperselect patients with CRC with unresectable, chemotherapy-naïve, 

 wild-type disease from the overall population for treatment with either panitumumab (Vectibix; n = 258) or bevacizumab with modified FOLFOX6 (n = 271) resulted in longer survival outcomes with panitumumab than those who presented with gene alterations. The median OS in the hyperselected population was 41.3 months (95% CI, 37.1-48.1) in the panitumumab group vs 34.4 months (95% CI, 31.3-40.3) in the bevacizumab group (HR, 0.75; 95% CI, 0.62-0.92).

The median OS in the gene-altered cohort of patients was 19 months (95% CI, 14.8-23.0) with panitumumab (n = 110) vs 22.2 months (95% CI, 19.1-27.7) with bevacizumab (n = 94; HR, 1.14; 95% CI, 0.84-1.54). Investigators then stratified patients by tumor sidedness in the hyperselected and gene-altered analyses (

“[Treatment] should be more fluid than defined, strict buckets of right and left,” Bekaii-Saab said. “This was beautifully done and justifies the importance of getting these liquid biopsies first.” He added that differences between liquid and tissue sampling may need further investigation because there are subgroups of patients who may not experience difference based on the type of sample. Marshall added that this is likely due to tumor shedding.

“The liquid [biopsy result] is giving you a sum of all tumors, and there’s some level of heterogeneity, whereas with tissue, you’re just hitting 1 [sample], which is probably accurate for [approximately] 85% of the patients. But for 15%, we’re missing the bigger picture at the beginning,” Bekaii-Saab said. “But we’re moving in a good direction in terms of understanding the interplay of these various mutations, alterations, and amplifications in CRC.”

As for the future of ctDNA in routine practice to determine pathways of adjuvant treatment for those who have resectable disease, Cohen noted that a study she and her colleagues performed highlighted the earliest timeline of testing post surgery.

 “At the 2023 ASCO GI [Cancers Symposium], we presented some information on cell-free DNA [cfDNA] and how that influences our detection of ctDNA,” Cohen said. “As much as we’re talking about the end results, the logistics [of testing] here are key. We’ve hinted at differences with tissue testing vs blood testing, but it all comes down to when that patient make[s] it into your clinic and how timely [you can perform testing] in relation to surgery. We’re looking at a 4- to 8-week window for adjuvant therapy. If we’re going to start incorporating ctDNA into our common testing strategies, we need those results and we need them as soon as we can get them.”

Tumor shedding after surgery may affect levels of ctDNA in patients post surgery; therefore, tumor-informed testing was conducted to assess the earliest window for ctDNA testing vs standard. “What our study did using the Signatera assay was to see when we can start sending that out [for accurate ctDNA analysis],” Cohen said. “We know that tumor-informed test [results] take a little longer [to come back].”

Within the first 2 weeks of surgery, an increase in cfDNA levels was observed, and this time 30.6% of patients showed a positive result for ctDNA. These rates were consistent with those observed during the standard MRD testing window of weeks 4 to 8 post surgery. Therefore, investigators concluded that standard MRD testing windows could be as early as 2 weeks after surgery or on day 15.

“This is key, because if we knew a patient was going to surgery, we could order tissue profiling to be done maybe even before they went to surgery, and we could get that blood draw 2 weeks later,” Cohen said about practice translatable to the clinic. “We could cut down some of the turnaround time for the tumor-informed assays…. This will help us start thinking through some of these processes on an individual institution level.”

NCCN. Clinical Practice Guidelines in Oncology. Colon cancer, version 2.2023. Accessed July 15, 2023. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf

Dedeurwaerdere F, Claes KB, Van Dorpe J, et al. Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer. 

. 2021;11(1):12880. doi:10.1038/s41598-021-91974-x

FDA approves encorafenib in combination with cetuximab for metastatic colorectal cancer with a BRAF V600E mutation. FDA. Updated April 9, 2020. Accessed July 15, 2023. http://bit.ly/3KysLlt

Kopetz S, Yoshino T, Kim TW, et al. BREAKWATER: an open-label, multicenter, randomized, phase 3 study, with a safety lead-in (SLI), of first-line (1L) encorafenib (E)+cetuximab (C)±chemotherapy (CT) vs standard-of-care (SOC) CT for BRAF V600E-mutant metastatic colorectal cancer (mCRC). 

. 2023;41(suppl 16):TPS3627. doi:10.1200/JCO.2023.41.16_suppl.TPS3627

Mukund K, Syulyukina N, Ramamoorthy S, Subramaniam S. Right and left-sided colon cancers - specificity of molecular mechanisms in tumorigenesis and progression. 

 2020;20(1):317. doi:10.1186/s12885-020-06784-7

Yoshino T, Watanabe J, Shitara K, et al. Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with 

 wild-type (WT) metastatic colorectal cancer (mCRC): results from the phase 3 PARADIGM trial. 

. 2022;40(suppl 17):LBA1. doi:10.1200/JCO.2022.40.17_suppl.LBA1

Cohen SA, Kasi PM, Aushev VN, et al. Kinetics of postoperative circulating cell-free DNA and impact on minimal residual disease detection rates in patients with resected stage I-III colorectal cancer. 

. 2023;41(suppl 4):5. doi:10.1200/JCO.2023.41.4_suppl.5

Articles

Emerging strategies leveraging biomarker data for the treatment of patients with early-stage and metastatic colorectal cancer have made precision medicine a top-of-mind topic for gastrointestinal oncologists.

Molecular Testing Drives Progress in CRC

Addressing socioeconomic health disparities has been a crucial objective of health policy in the United States. The relationship between cancer incidence and mortality and socioeconomic status varies across malignancies.

Risk factors associated with the development and progression of cancer, such as smoking, alcohol use, dietary habits, obesity, lifestyle choices, environmental pollution, and occupational exposure, are directly and indirectly influenced by an individual’s socioeconomic status and where they live. Although existing data indicate a higher incidence of breast cancer among those with higher socioeconomic status, limited information is available regarding the clinical outcomes of breast cancer based on neighborhood socioeconomic status.

Our research group at Roswell Park Comprehensive Cancer Center sought to clarify these possible connections. What we have found from our analysis of nationwide data underscores how imperative it is for clinicians to examine the relationship between neighborhood socioeconomic status and morbidity and mortality rates of specific malignancies.

Socioeconomic inequalities in cancer mortality are a global concern. Insufficient resources in areas with lower socioeconomic status contribute to delayed cancer diagnoses and inadequate treatment options, resulting in significant mortality and morbidity.

 Social factors, including income, educational and job opportunities, housing, social support, transportation barriers, and racial disparities also play a significant role in cancer-related mortality. These disparities are particularly pronounced in low- and middle-income countries where access to care and financial toxicity pose challenges for the majority of patients. Because of disparities in socioeconomic factors and developmental infrastructure, areas characterized by low individual and neighborhood socioeconomic status may be associated with poorer prognosis for certain malignancies.

Breast cancer is the most prevalent form of malignancy among women worldwide.

 Survival rates for patients with breast cancer are influenced by demographic, clinical, and pathologic factors. Additionally, racial and ethnic backgrounds as well as socioeconomic factors have been shown to effect clinical outcomes in breast cancer.

Using information compiled through the national cancer database, we conducted an analysis to explore the effect of neighborhood deprivation on clinical outcomes in breast cancer. Our findings were based on data from 88,572 patients throughout the US and revealed a higher prevalence of racial and ethnic minorities, particularly among individuals identifying as Black/African American or as Hispanic/Latinx, in areas characterized by greater deprivation compared with those not characterized as deprived. Likewise, the most deprived areas had a higher proportion of uninsured patients.

We observed predominant levels of aggressive subtypes of breast cancer, including HER2-positive and triple-negative breast cancer, as well as advanced disease stages, in the most deprived neighborhoods. Our analyses demonstrate that patients with early-stage breast cancer from areas with greater neighborhood deprivation experienced inferior overall and breast cancer-specific survival rates,

 after adjustment for common confounders effecting survival. Our findings were presented as a Poster Spotlight Discussion at the 2022 San Antonio Breast Cancer Symposium.

The identification of higher breast cancer stages in areas with the highest levels of deprivation raises concerns about delayed access to screening, insufficient insurance support, and inadequate education and awareness regarding general health among individuals residing in socioeconomically disadvantaged areas. Early detection of breast cancer is associated with improved prognosis, provided that appropriate care is delivered. Although our study results revealed a higher proportion of individuals representing racial and ethnic minorities in economically deprived neighborhoods, the disparity in survival rates persisted even after adjusting for patients’ race, ethnicity, and clinicopathological features. This highlights the significant role that both patients’ socioeconomic status and neighborhood characteristics play in determining breast cancer outcomes.

Our study findings have elucidated the critical effect of neighborhood deprivation on survival outcomes of patients with breast cancer. The cumulative impact of various neighborhood factors, such as infrastructure (eg, schools and hospitals), accessibility to nearby health care facilities, availability of healthy food and water, and neighborhood hygiene contributes to this phenomenon. Factors such as prolonged exposure to water and air pollution in underresourced neighborhoods can induce changes in the tumor microenvironment of individuals residing in those areas, potentially leading to the development of aggressive forms of breast cancer.

Unfavorable neighborhood conditions also can contribute to the emergence of chronic medical comorbidities, fostering an immunosuppressive tumor microenvironment that facilitates the development and progression of breast cancer.

Our work outlines strategies that can be implemented to effectively address these disparities as follows:

Enhance coordination among social workers and case managers at hospitals to identify and address barriers preventing patients from underresourced neighborhoods from accessing necessary care.

Implement government policies aimed at improving basic infrastructure in underresourced neighborhoods.

Deploy mobile mammography units to reach neighborhoods with limited access to health care, facilitating proper disease screening.

Provide free transportation services for patients residing in underresourced neighborhoods, ensuring their ability to attend regular appointments, receive treatment, and undergo necessary scans or radiation therapy.

Provide financial aid and support to patients with breast cancer from the most deprived neighborhoods and their families.

Implement community-based education and awareness programs in underresourced neighborhoods, focusing on breast cancer prevention, early detection, and the importance of regular screenings. These programs can be conducted in collaboration with local community organizations, schools, and health care providers to ensure widespread dissemination of information and empower individuals with knowledge to make informed decisions about their health.

Establish partnerships with local businesses and organizations to provide financial incentives and resources for breast cancer screenings and treatment in underresourced neighborhoods. Collaborating with community stakeholders, such as pharmacies, clinics, and charitable organizations, can help alleviate the financial burden associated with screenings and treatments. Such measures can involve offering discounted or subsidized mammograms, treatment medications, and supportive care services, as well as facilitating access to patient assistance programs or grants for individuals from disadvantaged backgrounds.

It is crucial for cancer clinicians to identify patients seeking breast cancer treatment from areas characterized by higher deprivation indices. This key step enables the implementation of strategies aimed at overcoming barriers related to financial status and transportation, thereby facilitating patients’ access to essential care, regular appointments, and vital diagnostic procedures, treatments, and follow-ups. These interventions hold significant potential to improve the clinical outcomes for patients with breast cancer.

Singh GK, Jemal A. Socioeconomic and racial/ethnic disparities in cancer mortality, incidence, and survival in the United States, 1950-2014: over six decades of changing patterns and widening inequalities. 

2017;2017:2819372. doi:10.1155/2017/2819372

Vaccarella S, Georges D, Bray F, et al. Socioeconomic inequalities in cancer mortality between and within countries in Europe: a population-based study. 

2023;25:100551. doi:10.1016/j.lanepe.2022.100551

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. 

Goel N, Hernandez A, Thompson C, et al. Neighborhood disadvantage and breast cancer-specific survival. 

2023;6(4):e238908. doi:10.1001/jamanetworkopen.2023.8908

Roy AM, George A, Attwood K, et al. Effect of neighborhood deprivation index on breast cancer survival in the United States. 

. Preprint posted online April 7, 2023. doi:10.21203/rs.3.rs-2763010/v1

Roy AM, George A, Attwood K, Gandhi S. Neighborhood deprivation index and survival in breast cancer in the United States. 

. 2023;83(suppl 5):PD1-04. doi:10.1158/1538-7445.SABCS22-PD1-04

Gearhart-Serna LM, Hoffman K, Devi GR. Environmental quality and invasive breast cancer. 

2020;29(10):1920-1928. doi:10.1158/1055-9965.EPI-19-1497

Saini G, Ogden A, McCullough LE, Torres M, Rida P, Aneja R. Disadvantaged neighborhoods and racial disparity in breast cancer outcomes: the biological link. 

2019;30(7):677-686. doi:10.1007/s10552-019-01180-4

Oncology Live®

Neighborhood Plays an Important Role in Clinical Outcomes for Patients With Breast Cancer

The implementation of a pharmacist-driven biosimilar substitution program across American Oncology Network institutions resulted in increased uptake of biosimilar agents as well as financial savings for payers, patients, and providers. Findings from a 1-year follow-up analysis were presented during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results showed that following the October 2021 initiation of the program, use of the biosimilar forms of bevacizumab (Avastin), trastuzumab (Herceptin), and rituximab (Rituxan) increased from less than 90% of administered doses to over 90% compared with their respective reference products by the December 2022 data cutoff. Uptake of the rituximab biosimilar was the most drastic, increasing from approximately 80% of administered doses at the program’s initiation to approximately 91% at the data cutoff, well above the 67% average for the United States. Trastuzumab uptake increased from approximately 89% at the program’s outset to approximately 92% at data cutoff, with bevacizumab climbing from approximately 90% to 97%; these figures bested both agents’ respective national average usage rates of 80% and 82%, respectively.

“Drugs for treating cancer account for the largest share of [Medicare] Part B drug spending, accounting for over half of spending in 2021,” Melody Chang, RPh, MBA, BCOP, the vice president of pharmacy operations at American Oncology Network, LLC, said in an interview with 

®. “It is important for us as community oncology practices to have a strategy for adopting biosimilars so we can stay competitive and be able to deliver [a higher] quality of care. [Additionally], many oncology practices participate in the value-based care or some sort of similar cost-sharing program. [Therefore], they are incentivized to decrease the total cost of care by using products such as biosimilars.”

Moreover, the cost savings attributed to the pharmacist-driven program were significant: From April 2021 to September 2021, payers saved approximately $8.0 million, patients saved approximately $2.0 million, and providers saved approximately $11.3 million, for a total savings of $21.3 million.

 Similarly, from October 2021 to April 2022, payers saved approximately $10.8 million, patients saved approximately $2.7 million, and providers saved approximately $10.6 million, for a total savings of $24.1 million attributable to the program’s implementation. Finally, approximate savings for the respective stakeholders increased significantly from January 2022 to December 2022, with the program in place for approximately a full year, at $26.4 million, $6.6 million, and $23.5 million, for a total savings of $56.5 million.

Biosimilars are agents based on reference products that have been previously licensed. These agents have no clinically significant differences regarding quality, safety, and efficacy compared with their reference products.

 “Even though biologics have significantly improved treatment outcomes, the trade-off is the high cost of these products,” Chang said. “The cost of biosimilars, however, is much lower, on average approximately 30% to 50% lower than the price of their originator, sometimes even [up to] 80% lower for some products.”

As of June 2023, 22 cancer or cancer-related biosimilar agents have been approved by the FDA, 12 for the treatment of cancer and 10 for use in a supportive care setting. The first biosimilar agent got the go-ahead from the agency in 2015.

Although biosimilars present a potentially massive opportunity to decrease the cost of care and improve patients’ access to effective treatment options, investigators have noted that to date there have been barriers to uptake and realizing actual cost savings for patients, payers, and providers. Challenges related to the adoption of biosimilars include knowledge gaps among clinicians or patients, relatively sparse data on long-term safety and efficacy, concerns with quality control or product variation, and sales and marketing tactics being applied by nonbiosimilar drug manufacturers to delay biosimilars’ time to market entry and prescription rates.

“Operational challenges can [also] happen to a manufacturer,” Chang said. “When a manufacturer is trying to scale up, they have to consider their resources. [For example], during COVID-19, we couldn’t [access] some biosimilars because manufacturers had to remove [parts of] the production line to produce products to treat or manage the COVID-19.”

The United States has lagged in biosimilar adoption compared with Europe, with the first biosimilar agent gaining approval in the European Union in 2006 and not until 2016 in the United States. The European Medicines Agency has approved 99 biosimilars overall, compared with 40 approved by the FDA in the United States. Biosimilar use led to an estimated list price savings of $8.5 billion in Europe by 2020 compared with the cost of reference agents.

The American Oncology Network, which was launched in 2018, is a partnership of over 100 physicians and more than 80 nurse practitioners and physician assistants that included participation from 18 states at the time of the analysis presented at the 2023 ASCO Annual Meeting. The network focuses on community practices providing innovative protocols to ease administration hurdles, enhance facilities, and improve care for patients with cancer. In June 2023, it was announced that Texas would become the American Oncology Network’s 19th state, with the addition of Lone Star Oncology in Georgetown, Texas.

The pharmacist-driven biosimilar substitution program was implemented in all American Oncology Network member institutions. According to Chang, approximately 33,000 doses of biosimilar agents were administered to 5000 individual patients across the network in a 12-month period during the course of the program. The 1-year analysis focused on the uptake of biosimilar bevacizumab, trastuzumab, rituximab, pegfilgrastim (Neulasta), and filgrastim (Neupogen).

As part of the program, regional clinical pharmacists acted as liaisons between providers and financial teams to estimate the financial impact of existing drug orders. “[Assessing] the payer coverage and a patient’s financial responsibility were handled by the financial team,” Chang said. “However, the result was processed through a pharmacist [who could] decide [which agent to use]. The provider doesn’t have to do anything; they just authorize the pharmacist to do it on their behalf. Then, we have a report generated so we can identify which patients are using our nonpreferred drugs. After identifying the patient and comparing the cost, a biosimilar switch request is generated. From the request, we automatically switch and the physician [makes an] acknowledgement before they approve the order, just like their normal process,” Chang explained.

Per the parameters of the analysis, payer savings were defined as the difference between the calculated 80% of the Medicare average sales price plus 6% for the given biosimilar vs the reference product. Patient savings were defined as the difference between the calculated 20% of the Medicare average sales price plus 6% coinsurance for the given biosimilar vs the reference agent. Finally, provider savings were determined by finding the difference between the invoiced cost of the biosimilar and the originator.

Additional findings from the analysis showed that use of biosimilar pegfilgrastim vs its reference agent rose from approximately 40% at the program’s initiation to just under 70% at the data cutoff, nearly double the national average of 37%. Interestingly, the uptake of biosimilar filgrastim rose from approximately 78% in October 2021 to a peak of approximately 92% in April 2022, before falling to approximately 55% at the data cutoff. Comparatively, the national average rate of usage of biosimilar filgrastim is 60%.

“That’s an interesting finding. We wanted to know why [there was a] reverse back from the biosimilar to the originator,” Chang said. “We looked at the cost of the drug, and [attributed it to] a change in the average sales price. We know the [use] of biosimilars is going to drive the cost down. In general, the average sales price will be more impactful for the cost calculation. It’s interesting, because we see the initial increase [in biosimilar filgrastim uptake] from October 2021 to May 2022, followed by a subsequent decrease from June [2022] to December [2022]. At third quarter of 2022, the biosimilar filgrastim average sales price had dropped [by] 81% from its launch price. During this time, despite the significant decrease in the average sales price of the biosimilar, our acquisition costs remained relatively unchanged. So acquisitions [prices] are not changed, but reimbursement drops. At the same time, the reference product average sales price remained relatively stable, meaning every time you use the biosimilar, your cost is higher than your reimbursement.”

In the future, Chang expects uptake in biosimilar use to steadily increase by way of growing awareness and clinical experience. Additionally, she said policy reform, such as the Inflation Reduction Act, could spark increased biosimilar use. As market competition intensifies, Chang noted that price reductions may anticipate it, leading some manufacturers to reallocate resources or scale back their patient support programs—which could represent a potential drawback.

“Our study demonstrated that a pharmacist-driven biosimilar program increased the adoption [of biosimilars] and the cost savings to all stakeholders,” Chang said. “However, there are still barriers, including the nonmedical switching required by payers because of the payer policy. Moving forward, we will continue this program and expand its coverage, [in order] to have a pharmacist assume the role of working collaboratively with our internal managed care team and the payer team when negotiating a contract or working together with the payers to remove some of the barriers, [such as] prior authorization, and reduce patient cost sharing.”

Chang M, Li J, Peters B, et al. Biosimilar uptake and cost savings analysis before and after implementation of a pharmacist-driven substitution program within a National Community Oncology Network: one-year follow-up. 

. 2023;41(suppl 16):6516. doi:10.1200/JCO.2023.41.16_suppl.6516

Rodriguez G, Mancuso J, Lyman GH, et al. ASCO policy statement on biosimilar and interchangeable products in oncology.

. Published online April 7, 2023. doi:10.1200/OP.22.00783

American Oncology Networkannounces Texas as new operating state with launch of community-based oncology clinic. News release. American Oncology Network. June 12, 2023. Accessed June 23, 2023. bit.ly/3JLpBt4

The implementation of a pharmacist-driven biosimilar substitution program across American Oncology Network institutions resulted in increased uptake of biosimilar agents as well as financial savings for payers, patients, and providers. 

Novel Program Provides Avenue for Increased Biosimilar Uptake, Reduced Cost

As new data emerge in breast cancer, stepping back from the updates and shedding light on the standard practices as they exist in the clinic are crucial approaches to management of the disease. For example, in early-stage, HER2-positive disease, small changes have rapidly improved outcomes for patients regardless of disease burden. With de-escalation strategies allowing for fixed-duration therapy in the pre- and postoperative settings, clinicians can provide less toxic treatment options for their patients. 

“We’ve come a long way over the past decade [in] treating [patients with] early-stage, HER2positive breast cancer, [and] we’ve learned that we can give therapy in the preoperative setting, [determine] how someone responds to that treatment, and then adapt their treatment after surgery based on that response,” Sara M. Tolaney, MD, MPH, said in an interview with OncologyLive. Tolaney is chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston, Massachusetts. Tolaney will serve as a faculty member during the 21st Annual School of Breast Oncology® meeting, hosted by Physicians’ Education Resource (PER), LLC. In her interview she noted that the meeting is one way in which clinicians can gain access to physicians who are translating the topline data into practice. 

“One thing I love about the School of Breast Oncology meeting is that there are many experts who know the field so well and provide the most up-to-date educational sessions on the [the most recent] data,” Tolaney said. “[Chair] Joyce O’Shaughnessy, [MD], does a phenomenal job bringing tough case discussions to the forefront [of the agenda]. These are cases that we struggle with in clinic, and it’s helpful to get guidance from very thoughtful clinicians who are there. The discussions with the cases are probably one of my favorite parts of the meeting.” 

Of focus in early-stage breast cancer are ways to ensure that patients are receiving the right amount of the optimal therapy for their disease. Clinicians are tackling this through 2 avenues, Tolaney said: de-escalation and biomarker-driven approaches. 

For example, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, findings from the 3-year follow-up of the PHERGain trial (NCT03161353) showed that the use of PET imaging may be a tool in early identification of patients with HER2-positive, early-stage breast cancer who may have a pathologic complete response (pCR) to neoadjuvant HER2-directed therapies. Using fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT, investigators traced patients for early metabolic response to de-escalate chemotherapy in the neoadjuvant setting.

Patients were administered pertuzumab (Perjeta) and trastuzumab (Herceptin) with or without endocrine therapy—letrozole for those who were postmenopausal and tamoxifen for those who were premenopausal—for 2 cycles before undergoing 18F-FDG PET/CT. 

If patients demonstrated a response, they continued therapy with no changes. If there was no response, patients proceeded to chemotherapy/antibody therapy of TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) for 6 cycles. Patients then proceeded to surgery, and those in the TCHP arm went on to pertuzumab/ trastuzumab with or without endocrine therapy, and those in the original therapy arm were assigned based on pCR to either continue therapy (pCR) or to TCHP (no pCR). 

Among all evaluable patients in the intentionto-treat population at the time of surgery (n = 267) the 3-year invasive disease-free survival (iDFS) rate was 95.4% (95% CI, 92.8%-98.0%). Additionally, the 3-year event-free survival (EFS) and overall survival (OS) rates in the overall population (n = 285) were 93.5% (95% CI, 90.7%-96.5%) and 98.5% (95% CI, 97.1%-100%), respectively.1 For comparison, in the arm evaluating TCHP for 4 cycles prior to surgery, [among those who received] pertuzumab/trastuzumab with or without endocrine therapy after surgery regardless of response (n = 63) had an iDFS rate of 98.3% (95% CI, 95.1%-100%) at the time of surgery. In evaluable patients from the overall cohort of this regimen (n = 71), the EFS and OS rates were 98.4% (95% CI, 95.3%-100%) and 98.4% (95% CI, 95.3%100%), respectively.

Another avenue of prognostication comes in the form of an assay, the HER2DX genomic risk score, which has been examined in exploratory analyses of pivotal HER2 breast cancer studies.

 The algorithm to develop the score, the aim of which is to stratify patients with earlystage disease into low- and high-risk groupings for recurrence, uses “4 gene expression-based signatures to track adaptive immune cell infiltration, tumor cell proliferation, HER2 amplicon expression and tumor cell luminal differentiation, together with tumor stage (T1 vs T2 vs T3/ T4) and nodal stage (N0 vs N1 vs N2/N3).”2 

Tolaney and colleagues published findings of an analysis in The Lancet Oncology using the tool in an analysis of findings from the phase 2 APT trial (NCT00542451). When applying the tool, the authors wrote, “HER2DX risk score as a continuous variable was significantly associated with iDFS (HR per 10-unit increment, 1.24 [95% CI, 1.00-1.52]; P = .047) and recurrence-free interval (HR, 1.45; 95% CI, 1.09-1.93]; P = .011).”

: What are the current treatment approaches for early-stage, HER2-positive breast cancer?

We know this paradigm—our current treatment approach is to give a patient with stage II/ III, HER2-positive breast cancer preoperative treatment. The standard at this time is TCHP for 6 cycles, take them to surgery, and if they have a pCR, then continue the trastuzumab and pertuzumab. They get a complete year of therapy, or if they have residual disease, we give them T-DM1 [ado-trastuzumab emtansine (Kadcyla)] for 14 cycles.

If [we] have patients with stage I [disease]— someone with a small tumor that’s clinically node negative—we often [go straight to] up-front surgery, and then give them adjuvant therapy. [Once] we’ve confirmed that they have a stage I cancer, the choices would be to give weekly paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy, or to give T-DM1 for 17 doses. Either of those approaches would be reasonable for that patient.

What are the benefits of dual HER2 blockade in the neoadjuvant and adjuvant settings?

We have learned that we can add pertuzumab to chemotherapy and trastuzumab. Originally, the data focused on the benefits of adding pertuzumab in the preoperative setting. For example, we had data from studies such as NeoSphere [NCT00545688] and TRYPHAENA [NCT00976989] that taught us that adding pertuzumab to chemotherapy and trastuzumab improved pCR. This was really important to understand, and it led to the initial FDA approval of pertuzumab based on improvement in pCR. But in truth, we really wanted to know whether adding pertuzumab would improve survival outcomes. And those data came from the APHINITY trial [NCT01358877], which taught us that adding pertuzumab to chemotherapy/ trastuzumab improved iDFS. Now, with over 8 years of follow-up [data, the regimen] still has not improved OS, and the benefits for adding pertuzumab were restricted to those patients with node-positive disease, with no benefit from adding pertuzumab in a patient with node-negative disease.

Are de-escalation treatment strategies viable, and how would you characterize optimal patient care? 

We’re fortunate because we have seen multiple new HER2-directed agents come along that have dramatically improved outcomes. We’ve added pertuzumab, we know how to use T-DM1, and we already had trastuzumab. Now that we have this armamentarium, we realize that maybe we can achieve the same efficacy, with decreased toxicity, if we tailor therapy to the individual patient.

For example, when we thought of small HER2positive cancers, we learned we can give an abbreviated amount of chemotherapy—12 weeks of paclitaxel—and achieve great outcomes.

Now we’re wondering whether there are other ways we can tailor therapies. One way we are trying to do this is by [asking]: Can we give a certain regimen in the preoperative setting, and if the patient achieves a pCR, can we say that that was enough therapy? For example, [if a patient receives] THP for approximately 12 weeks and has a pCR, can they do their adjuvant 9 months of HP therapy and achieve good outcomes? In essence, can we de-escalate from TCHP to THP in those who achieve pCR? That’s one such approach in an ongoing trial called CompassHER2-pCR [NCT04266249].

Some [investigators] call them de-escalation trials, others call them optimization trials, but a lot of these trials have been trying to tailor therapy based on response. [Regardless] what we’re trying [to ask] with these trials is whether we can go a step further and tailor therapy by looking at response prior to surgery. 

At ASCO [we saw some data] from the PHERGain trial, [which uses] PET response to help us tailor [therapy]. And then I think we’re trying to even move toward biomarker-driven trials to help tailor therapy. There’s a new biomarker [risk score] called HER2Dx, which seems to help us predict who’s going to achieve pCR and who’s going to have good long-term outcomes.

In HER2-positive disease, is tumor biology more important than the size of the tumor? What are examples of a biomarker-driven treatment approach?

Whether size matters is an important question, and I do think size does still matter. If you look at patients who achieve pCR to HER2-directed therapy, we know that’s a good thing because if there is pCR, there likely [will be] very good long-term outcomes. But we know that not all pCRs are the same.

If you take a patient who started with a big tumor and who had multiple positive lymph nodes, and they achieved pCR—and you compare their outcomes with [those of] someone with a small cancer with no lymph node involvement up front—even though they both had all their cancer gone at the time of surgery, the person who started with higher clinical and anatomic risk has higher risk of recurrence. To me that suggests that biology does matter, but so does size because that tumor was clearly very sensitive to HER2-directed therapy because they achieved pCR. But their clinical anatomic risk did put them at still higher risk of recurrence. 

So if we go back to that example, looking at HER2DX, [for] that score, where [investigators] looked at 4 different gene expression signatures, they add tumor size and nodal status. That is key because, again, you use biology, you use clinical risk, and you come up with the best outcome prediction that you can.

Are there any treatments on the horizon that could affect standards of care?

Next, the question [of whether] trastuzumab deruxtecan could replace all preoperative chemo-therapy [arises]. There’s a trial that’s looking at replacing ACTHP [doxorubicin hydrochloride, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab] with trastuzumab deruxtecan—so either replacing the whole duration of ACTHP with [the antibody-drug conjugate], or replacing half of it, replacing the AC with 4 cycles of trastuzumab deruxtecan, then following up with THP.

Trastuzumab deruxtecan does seem very promising given what we’ve seen in the metastatic setting. There certainly are some toxicity concerns that come up, particularly the risk of interstitial lung disease. We will have to look at the efficacy data from these trials and balance those with potential toxicity to figure out how [trastuzumab deruxtecan] fits in. But I do think that it has potential to change standard [treatment]. 

There’s also interest in looking at tyrosine kinase inhibitors in the early-stage setting. For example, CompassHER2 RD [NCT04457596] is looking at adding tucatinib [Tukysa] to T-DM1 with the hope that it will improve diseasefree survival and help prevent CNS [central nervous system] recurrence because it has CNS penetration.

Can you speak to the importance of the multidisciplinary approach and the breast cancer space? 

Multidisciplinary care in breast cancer is critical right now. When we see patients with newly diagnosed breast cancer at Dana-Farber, for example, we see them in combination with our surgical oncologist and sometimes a radiation oncologist up front with the medical oncologist. 

The reason is that these [treatment] decisions are complicated. Does it make sense for the patient to get systemic therapy before surgery?... We need to have that as a discussion [with the team]. What about additional tests that need to be done before preoperative therapy? Do they need a lymph node biopsy? What if there’s an area on imaging that the surgeon is concerned about and they want a biopsy to understand whether the patient is going to be a breast conservation candidate? 

Even more complicated is this whole issue about nodal evaluation at the time of surgery. [For example,] can a patient get away with sentinel node [biopsy] alone? Do they need an x-ray dissection? Will [those results] influence decisions regarding radiation? Could that change systemic therapy recommendations? It’s just so complicated. So it’s really nice to have these multidisciplinary discussions with our colleagues so that we make the right decisions for the individual patient.

Looking ahead to the next 5 years, what are some unmet needs that you hope to see resolved?

We’ve been successful in early-stage, HER2positive disease, where we are curing more and more patients, and we’re doing so in a way where toxicities are being thoughtfully considered. That said, I think we are giving some patients too much therapy and some too little therapy. Where I’d love to see us go is to figure out how to really optimize treatment and personalized care. 

Biomarkers will help us get there, but we also need to be bold in our clinical trial designs. We’re learning how to do de-escalation studies, but they’re tricky because you don’t want to undertreat a curable patient and leave them with a recurrence. [These trials] have to be done thoughtfully. Certainly we all always want to get patient advocates involved in such designs as well. 

The optimal duration of HER2-directed therapy is still not known. We’ve done multiple trials, but we’re still giving 1 year of trastuzumab-based treatment. Does everyone really need that? Can some patients get away with less? Who’s going to need trastuzumab deruxtecan? [Eventually] we’re going to need to figure that out because, again, there are potential toxicities [and we want to know whether there are those] who can get away with less toxic regimens. And who can get away with no chemotherapy? I do think there are patients who can get away without any chemotherapy at all and just [receive] antibodies. But we don’t have robust enough predictors for that, and we need to get there. I think we’ll continue to see things evolve as we learn how to integrate biomarkers into the early-disease setting.

Cortes J, Pérez-García JM, Ruiz-Borrego M, et al. 3-year invasive disease-free survival (iDFS) of the strategy-based, randomized phase II PHERGain trial evaluating chemotherapy (CT) de-escalation in human epidermal growth factor receptor 2-positive (HER2[+]) early breast cancer (EBC). J Clin Oncol. 2023;41(suppl 17):LBA506. doi:10.1200/JCO.2023.41.17_suppl.LBA506 

Prat A, Guarneri V, Pascual T, et al. Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer. EBioMedicine. 2022;75:103801. doi:10.1016/j. ebiom.2021.103801 

Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24(3):273-285. doi:10.1016/S14702045(23)00051-7

As new data emerge in breast cancer, stepping back from the updates and shedding light on the standard practices as they exist in the clinic are crucial approaches to management of the disease.

Advances in Early-Stage Breast Cancer Pull Biology and Biomarkers Into Focus

An evaluation of the utility of a cancer therapeutic in a clinical trial is determined through metrics that define 2 distinctive features of an antineoplastic strategy: 

. Although that may be an oversimplification, the aim of such therapy is to improve clinical outcomes. It is therefore understandable that in most settings, there is a greater focus on the evaluation of efficacy, with toxicity often relegated to high-level and often quite subjective conclusions. For example, it is common for investigations to declare that a regimen is 

 or to use the even more ill-defined description of 

It is relevant to note the relative precision used to analyze the metrics employed in an evaluation of efficacy, which can include progression-free and overall survival, as well as imaging-based objective response rates. In contrast, the multiple potential organ- and function-based toxicities are graded on scales that may appear, to some, to be compromises worked out by a large committee of cancer experts. It is uncertain that input (if any) from patients with cancer who may have experienced or been at risk to experience the adverse effects (AEs) was considered.

The potential for antineoplastic therapeutics to have off-target effects on organs has always been a concern. However, the magnitude of concern highlighted here is a relatively recent phenomenon In the recent past, routinely anticipated serious toxicities were most common in the hematopoietic system (ie, white and red blood cells, platelets) and the gastrointestinal tract (ie, emesis, diarrhea, stomatitis/mucositis).

The negative effects were either easily quantifiable (eg, peripheral blood counts), evaluable (eg, severity of acute emesis and diarrhea), or both. In addition, dose modifications were generally—but certainly not always—effective at reducing the deleterious effects of the therapeutic. Even the more chronic serious cardiac toxicity associated with doxorubicin was able to be reasonably predicted and the risk reduced by routine cardiac monitoring during treatment.

Therefore, it is important to inquire as to what has changed in the cancer management arena to justify the concern for the evaluation of antineoplastic drug AEs highlighted in this commentary.

First, the AE profiles of many of the antineoplastics recently introduced to the clinic are substantially different from those of the era when alkylating agents, platinum drugs, anthracyclines, and other cytotoxics were foundational in the care of advanced and metastatic cancers. For example, checkpoint-inhibiting immunological agents widely employed today have a remarkably different AE profile compared with the cytotoxic drugs they now replace or are administered in a combination regimen.

 This statement is not to suggest this class is more toxic than the older drugs, but rather that when serious AEs develop, they are often different from those observed with these agents alone.

Another example of unique antineoplastic drug toxicity is seen with the combination of an antibody targeted to a cell receptor linked to a cytotoxic payload. Ocular toxicity, uncommonly noted as an AE of standard antineoplastic drug therapy, has been an observed prominent AE in this setting.

Second, management of many cancers has evolved from 

 (eg, 4 to 6) of intermittently delivered antineoplastic drug courses (eg, every 3 to 4 weeks) to viewing the condition in many settings as a more 

 where treatment may be continued for extended periods, possibly measured in years. Under such circumstances, more chronic or lower-grade AEs that develop or slowly worsen over an extended period or reoccur with each treatment cycle may become highly clinically relevant.

Third, the availability of effective oral antineoplastic agents delivered daily or several times each day, such as PARP inhibitors, as a 

 strategy may pose different and particularly challenging concerns.

 For example, grade 1 nausea experienced for several days following treatment with cisplatin may be reasonably considered a major victory (and success of prophylactic antiemetic therapy), but the same grade 1 nausea experienced after each dose of a twice-a-day oral antineoplastic administered continuously for several years may be quite a different story. In fact, serious concern has been raised for the actual extent of patient adherence to many effective oral antineoplastic drug regimens.

Fourth, in randomized trials examining a novel agent against a cytotoxic chemotherapeutic, the percentage of patients who experience the more serious AEs (grade 3 or 4) is often reported as a comparison between the strategies. But is this a meaningful comparison when one is comparing symptomatic events impacting organ function vs appropriately managed and largely (but certainly not exclusively) asymptomatic bone marrow suppression?

Finally, it is relevant to acknowledge that the effect of AEs on an individual’s overall quality of life in a chronologically or physiologically younger or otherwise healthier patient with cancer may be far different from that experienced by a patient with a compromised performance status. How this factor might be considered in the assessment of observed toxicity in a cancer trial is a topic worthy of discussion.

There is no intent here to criticize any pharmaceutical or biotech company in their drug developments efforts or the way observed drug AEs are discussed by clinical investigators in the oncology literature employing current standard definitions and grading scales. But is it truly rational to classify nausea that results in a “loss of appetite” or “decreased oral intake” as reported in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 that 

occurs after each daily dose taken for several years

In a discussion with a patient who has treatment planned with an agent that may result in ocular toxicity, does a grade 2 label appear appropriate for the experience of “symptomatic” blurred vision or keratitis that is “symptomatic with medical intervention indicated” as defined in the NCI CTCAE, version 4.0?

Considering the substantial recent developments in the current management of malignant disease as well as concerns with providing optimal quality care to individual patients, is it time for the oncology community to engage in a comprehensive review of how toxicity is evaluated and graded in the conduct of cancer clinical trials?

Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. 

. 2021;39(36):4073-4126. doi:10.1200/JCO.21.01440

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. 

An evaluation of the utility of a cancer therapeutic in a clinical trial is determined through metrics that define 2 distinctive features of an antineoplastic strategy: efficacy and toxicity. Although that may be an oversimplification, the aim of such therapy is to improve clinical outcomes. 

Vol. 24/No. 13 | Oncology Live®

Molecular Testing Drives Progress in CRC

Neighborhood Plays an Important Role in Clinical Outcomes for Patients With Breast Cancer

Novel Program Provides Avenue for Increased Biosimilar Uptake, Reduced Cost

Advances in Early-Stage Breast Cancer Pull Biology and Biomarkers Into Focus

Evaluating Toxicities of Antineoplastic Drug Therapeutics: Is It Time for a Critical Review?