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Dramatic changes are occurring as health care evolves into value-based care, bringing a focus on quality. The US Oncology Network (The Network)— one of the nation’s largest networks of integrated, community-based oncology practices—plays a pivotal role in this transformation. The Network, supported by McKesson, is dedicated to advancing evidence-based, patient-centered care through innovative quality measures and comprehensive support services. The use of patient-reported outcome measures—the gold standard in quality measurement—is crucial to building a patient-centered, value-based care system.

Historically, health care has relied on clinically focused quality measures to check whether an activity thought to improve care was completed. However, the activity does not necessarily result in definitive improvement. Now health care is transitioning to a more holistic approach, with a goal of not only managing disease but also identifying and resolving health-related social needs (HRSNs) that can negatively affect care. The care team plays a key role in helping patients address HRSNs, but there has not been a systematic way to capture and analyze data and follow through to confirm issues were alleviated or resolved.

Patient-reported measures addressing HRSNs can play a vital role in transforming health care to a new, higher level of care focusing on the whole person. McKesson, in collaboration with The Network, which has more than 2600 providers and 600 sites of care across the US,

 is committed to advancing health care with a more holistic approach by developing a patient-reported quality measure. The goal is not only to identify patients’ HRSNs but also to assess whether those needs were addressed and/or resolved and if improvements were seen. A closer look at HRSNs, as well as a glimpse at McKesson’s new measure, may provide insight into why these types of quality measures are essential if value-based care is to succeed.

HRSNs are defined as social and economic needs patients experience that affect their ability to maintain their health and well-being. This can include impacts on adherence to treatment plans or access to health care services and needs such as housing, food, personal safety, transportation, and affordable utilities.

When problems arise in these areas, patients may face challenges obtaining care or completing treatment. Helping patients overcome these hurdles enables them to focus on their treatment, which supports optimal outcomes and increases access to care. Research also demonstrates outcomes and health equity improve when patients’ needs, such as screening, are met.

 Marginalized populations are disproportionately affected by HRSNs, leading to health disparities.

 Clinicians can help reduce inequities with interventions such as support services, or they can connect patients with resources, helping to create more equitable outcomes.

Proactively addressing HRSNs can also create cost savings. Emergency department visits and hospital admissions caused by complications from unmet social needs can be reduced. Additionally, savings may occur through investments in interventions promoting preventive care and better disease management.

Patient feedback is an important component of health care that can be used to measure quality of care.

 Patient-reported outcome measures are an efficient way to aggregate information from patients into a valid measure of performance, making this a valuable tool for assessing interventions. Patients tend to be more forthcoming when reporting information themselves, providing a more accurate picture of their situation and enabling providers to personalize interventions. When care team members work with patients to identify a need and provide support and/or resources, patients feel their concerns are acknowledged. This often enhances the relationship and patients’ confidence in their care team.

Significant value for patients with cancer can be achieved from measures that strive to resolve or improve HRSNs, as patients often face difficult challenges, including financial issues, emotional distress, isolation, and limited support services. Outcomes and quality of life can be positively affected by addressing these needs.

Patients’ perspectives and experiences collected by patient-reported measures empower a holistic assessment, drive patient-centered care, and support monitoring of treatment outcomes. Evidence shows that the integration of patient-reported outcome measures into routine clinical practice can improve symptom management, quality of life, and satisfaction for patients.

 Consequently, as health care evolves, incorporating patient-reported outcome measures will be vital in addressing needs and improving the overall well-being of patients.

New Measure Examines Whether Needs Are Met

McKesson’s Patient-Reported Outcomes-Based Performance Measure (PRO-PM)—aimed at improving or resolving HRSNs—is the latest step in the organization’s commitment to develop meaningful, oncology-specific measures that drive improvements in care while streamlining participation in the Merit-based Incentive Payment System (MIPS). Designated by the Centers for Medicare & Medicaid Services (CMS) as a qualified clinical data registry (QCDR), for the past 8 consecutive years McKesson has been certified to develop custom quality measures that are impactful to oncology. With the company’s CMS-approved QCDR platform, Practice Insights, clinicians can participate in the MIPS program by using both MIPS and custom QCDR quality measures that are more specific and meaningful to oncology.

The new HRSNs measure from McKesson is unique. It will be the first patient-reported outcome quality measure available to oncologists and all practices participating in MIPS that examines whether practices achieved improvement or resolution of an HRSN noted by the patient and documented in the medical record. The goal is to have the measure approved by CMS for the 2025 MIPS program.

There are several reasons why the measure is important. First, it examines outcomes rather than processes, reporting on whether an improvement occurred. Secondly, it focuses on addressing HRSNs recognized as highly important to patient care, especially in oncology. When needs are met, patients are more likely to achieve better outcomes and experiences.

The process to develop the measure was carefully planned and executed using input from many angles. The Network’s extensive clinical experts and its frontline experience in patient care were instrumental in shaping the measure, ensuring it will be meaningful, comprehensive, and feasible to implement. A multidisciplinary workgroup was formed that included subject matter and technology experts, plus clinical staff from The Network. Feedback was gathered from patient navigators, social workers, and a physician steering committee within The Network to ensure the measure would be practical in the real world. Measure development can take a long time, but due to the wide range of experts within McKesson and the clinical expertise of The Network, specifications were developed within a few months, and the measure is planned for release in early 2025.

Social workers, navigators, and nurses within The Network have been gathering information on HRSNs for years and helping patients remove barriers to care, but they’ve received little recognition for their valuable contributions. What was done for years in the background by these dedicated professionals will now be brought to the forefront. With McKesson’s PRO-PM, there will be a systematic way to capture HRSN information, address it, track improvements, and then report on the progress or gaps in care.

The education and expertise of the care team— especially social workers—empower them with skills to build a strong relationship with patients. Therefore, they are ideally suited to influence patient care and address patient HRSNs. These experienced communicators help patients identify barriers that are inhibiting care, and they work with patients to navigate those issues. As patient advocates, they also help clinicians understand the patient’s right to self-determination when care recommendations differ from the patient’s choice.

Although the care team has always identified and worked to resolve HRSNs, the challenge now is the massive volume they face. In the past, they received referrals or identified patients on their own. Today all patients are screened, so promptly addressing everyone’s needs has become difficult.

Additionally, there are needs that cannot be met, since different communities have different resources. It is important for practices to strive for high performance in these outcome measures to show improvement, but it is equally important to identify where there are shortages, limitations, or inabilities to meet patients’ needs. A quality measure such as McKesson’s will identify regions unable to show improvements due to lack of resources.

Other quality measures screen for HRSNs, but McKesson’s is the first submitted to CMS for approval that addresses the ability to resolve issues after they have been identified. Feedback from clinical staff indicates they appreciate being able to determine whether patient needs were met. McKesson’s measure moves the needle, allowing clinicians to not only identify needs, but efficiently follow through, capture information, and report on results.

McKesson’s support of The Network, which serves more than 1.4 million patients with cancer annually, brings together experts in technology development with those in the clinical space, creating the ideal scenario for quality measure development. Both are committed to advancing cancer care in this new era of managing HRSNs. McKesson’s new quality measure is the first of many more to come aimed at meeting patients’ needs, ultimately improving outcomes and reducing health care inequities. 

Accelerating the use of patient-reported quality measures in value-based care. Health Care Transformation Task Force. Accessed July 24, 2024. https://hcttf.org/wp-content/uploads/2023/11/Accelerating-the-Use-of-Patient-Reported-Quality-Measures-in-Value-Based-Care.pdf

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Addressing health related social needs in communities across the nation. US Department of Health and Human Services. November 2023. Accessed July 25, 2024. https://aspe.hhs.gov/sites/default/files/documents/3e2f6140d0087435cc6832bf8cf32618/hhs-call-to-action-health-related-social-needs.pdf

Patient navigation services increase cancer screening and advance health equity. US Department of Health and Human Services. Updated June 2024. Accessed July 25, 2025. https://health.gov/healthypeople/tools-action/browse-evidence-based-resources/patient-navigation-services-increase-cancer-screening-and-advance-health-equity

Health care access and quality: evidence-based resources. US Department of Health and Human Services. Accessed July 25, 2025. https://health.gov/healthypeople/objectives-and-data/browse-objectives/health-care-access-and-quality/evidence-based-resources

Baah FO, Teitelman AM, Riegel B. Marginalization: conceptualizing patient vulnerabilities in the framework of social determinants of health–an integrative review. 

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Graboyes EM, Lee SC, Lindau ST, et al. Interventions addressing health-related social needs among patients with cancer. 

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Patient-reported outcome measures. CMS.gov. December 2023. Accessed July 26, 2024. https://mmshub.cms.gov/sites/default/files/Patient-Reported-Outcome-Measures.pdf

Valsangkar N, Fernandez F, Khullar O. Patient reported outcomes: integration into clinical practices. 

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McKesson’s practice insights designated as a 2024 qualified clinical data registry by Centers for Medicare & Medicaid Services. McKesson. February 8, 2024. Accessed August 8, 2024. https://www.mckesson.com/about-mckesson/newsroom/press-releases/2024/mckessons-practice-insights-designated-2024-qualified-clinical-data-registry-centers-medicare-medicaid-services/

Articles

The transition to value-based care emphasizes quality and patient-centered approaches, with The US Oncology Network playing a crucial role. McKesson, in collaboration with The Network, is advancing patient-reported outcome measures to address health-related social needs (HRSNs), which impact patient outcomes and costs. The new Patient-Reported Outcomes-Based Performance Measure (PRO-PM) aims to improve or resolve HRSNs, focusing on outcomes rather than processes. This measure, developed with input from clinical experts, will be the first of its kind for oncologists participating in the Merit-based Incentive Payment System (MIPS).

Partner Perspective

The use of patient-reported outcome measures—the gold standard in quality measurement—is crucial to building a patient-centered, value-based care system.

McKesson's Patient-Reported Outcomes Measure Will Track Improvements in Health-Related Social Needs

New data with TROP2-targeted therapy showing reduced rates of myelosuppression have fueled enthusiasm for TROP2-directed antibody-drug conjugates (ADCs) for patients with breast cancer and other solid tumors, strengthening the evidence in support of the class’s safety and efficacy.

The first indication for a TROP2-directed ADC came in 2020 when the FDA granted accelerated approval to sacituzumab govitecan-hziy (Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC).

 TROP2 is highly expressed in multiple epithelial cancers and is involved in intracellular signaling via multiple pathways, including MAPK, PI3K/AKT, ERK, and JNK. These pathways are often associated with the proliferation, spread, and invasion of cancer cells.

“TROP2 is a cell surface transmembrane protein that is seen in normal tissues, but overexpressed in cancers,” Ian Krop, MD, PhD, explained in an interview with 

. “In cancers, it’s been shown functionally to lead to higher proliferation rates and less apoptosis, meaning better survival of the [cancer] cells. Overexpression [of TROP2] in cancer has been associated with poor prognosis. All those [factors] make it an attractive target for anticancer therapies.”

Krop is the director of the Clinical Trials Office, chief clinical research officer and associate director of clinical sciences at Yale Cancer Center, and a professor of internal medicine (medical oncology) at Yale School of Medicine in New Haven, Connecticut.

Sacituzumab govitecan is currently the only TROP2-directed ADC approved by the FDA. Following the 2020 accelerated approval of the agent for the treatment of patients with mTNBC who received at least 2 prior therapies for metastatic disease, the indication was converted to a regular approval in April 2021 for the treatment of patients with mTNBC who underwent 2 or more prior systemic therapies, with at least 1 of them for metastatic disease. Also in April 2021, the FDA granted accelerated approval to the ADC for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received platinum-containing chemotherapy and a PD-L1 inhibitor. Finaly, in February 2023, the FDA approved sacituzumab govitecan in hormone receptor–positive, HER2-negative breast cancer following endocrine-based therapy and at least 2 other systemic treatments in the metastatic setting.

“[These indications for sacituzumab govitecan] highlight that these are cancers where TROP2 is overexpressed and thus a TROP2-[directed] ADC…could have a therapeutic role,” Aditya Bardia, MD, MPH, FASCO, director of translational research integration and a professor in the Department of Medicine, Division of Hematology/Oncology at UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California, noted in a separate interview with 

. “There are [also] a number of additional drugs in development.”

Dato-DXd Stirs Excitement for TROP2-Directed Therapy in Breast and Lung Cancer

Beyond sacituzumab govitecan, the TROP2-targeted ADC that is furthest along in the development pipeline is datopotamab deruxtecan (Dato-DXd). “Dato-DXd is a TROP2-directed ADC with a more stable linker that more selectively delivers deruxtecan to tumor cells. It has a bystander effect and can [also] affect other cells that do not express TROP2,” Bardia explained (

The ongoing phase 1 TROPION-PanTumor01 study (NCT03401385) is the first in-human trial of Dato-DXd. The study is enrolling patients with previously treated advanced solid tumors, including hormone receptor–positive, HER2-negative breast cancer and TNBC. Updated findings from the study showed that treatment with Dato-DXd led to overall response rates (ORRs) of 26.8% (95% CI, 14.2%-42.9%) and 31.8% (95% CI, 18.6%-47.6%) in patients with hormone receptor–positive, HER2-negative breast cancer (n = 41) and TNBC (n = 44), respectively. The median progression-free survival (PFS) was 8.3 months (95% CI, 5.5-11.1) and 4.4 months (95% CI, 3.0-7.3), respectively.

“The evidence of clinical activity was encouraging, and there are ongoing phase 3 trials,” Bardia noted. “In terms of safety profile, the rate of myelosuppression was low with Dato-DXd, which is in contrast to the other TROP2-[directed] ADCs, such as sacituzumab govitecan, [which has] high rates of myelosuppression.”

The positive data from TROPION-PanTumor01 led to the initiation of the phase 3 TROPION-Breast01 study (NCT05104866), which is investigating Dato-DXd in patients with inoperable or metastatic hormone receptor–positive, HER2-negative breast cancer who experienced disease progression with endocrine therapy and have received 1 or 2 prior lines of chemotherapy. Findings from the primary analysis of the study, presented during the 2023 European Society for Medical Oncology Congress, demonstrated that patients who received Dato-DXd (n = 365) achieved a significant PFS benefit compared with those who received investigator’s choice of chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; 

“The [safety] profile [of Dato-DXd] is manageable; it’s interesting [because] it’s quite different than that of sacituzumab govitecan,” Krop added. “Sacituzumab govitecan’s toxicity most notably [consists of] neutropenia, as well as some gastrointestinal toxicities. With Dato-DXd, even though it has the same target and the same class of payload [as sacituzumab govitecan], we see little clinically meaningful toxicity in [terms of] hematologic values. Stomatitis [was reported in approximately] 50% of patients [who received Dato-DXd but] it’s almost all grade 1 or 2. Although there was a small percentage of patients with grade 3 or higher stomatitis, it didn’t lead to a significant number of patients discontinuing the drug.”

Findings from TROPION-Breast01 led to the FDA accepting the biologics license application (BLA) for Dato-DXd in April 2024 for the treatment of adult patients with unresectable or metastatic hormone receptor–positive, HER2-negative breast cancer who have received prior systemic treatment for unresectable or metastatic disease. The Prescription Drug User Fee Act (PDUFA) action date is January 29, 2025.

Dato-DXd is also being evaluated in a phase 3 study for the treatment of patients with non–small cell lung cancer (NSCLC). During the 2024 International Association for the Study of Lung Cancer World Conference on Lung Cancer (WCLC 2024), investigators shared updated findings from the phase 3 TROPION-Lung01 study (NCT04656652). TROPION-Lung01 is examining Dato-DXd vs docetaxel in patients with previously treated metastatic NSCLC with or without actionable genomic alterations.

Prior data from TROPION-Lung01 met the study’s coprimary end point of PFS, showing a significant improvement with Dato-DXd vs docetaxel (HR, 0.75; 95% CI, 0.62-0.91; 

 = .004). These findings supported the FDA’s acceptance of the BLA for Dato-DXd for the treatment of adult patients with previously treated, locally advanced or metastatic nonsquamous NSCLC in February 2024, with a PDUFA date decision expected in the fourth quarter of 2024.

Data from the final overall survival (OS) analysis of the study presented during WCLC 2024 showed that patients who received Dato-DXd (n = 299) experienced a median OS of 12.9 months (95% CI, 11.0-13.9) compared with 11.8 months (95% CI, 10.0-12.8) among patients treated with docetaxel (n = 305; HR, 0.94; 0.78-1.14; 

 = .530), missing the study’s second coprimary end point. However, Dato-DXd did provide a non–statistically significant OS benefit vs docetaxel in the subgroup of patients with nonsquamous histology, reducing the risk of death by 16% (HR, 0.84; 95% CI, 0.68-1.05); investigators concluded that the agent could be a new therapeutic option for this patient population.

Additionally, investigators presented an analysis of TROPION-Lung01 during WCLC 2024 that examined the predictive value in terms of clinical outcomes of TROP2 expression by normalized membrane ratio (NMR) per quantitative continuous scoring (QCS). Data from the analysis showed that patients positive for TROP2 expression by QCS-NMR who received Dato-DXd (n = 107) achieved a median PFS of 6.9 months compared with 4.1 months among patients in this group who received docetaxel (n = 107; HR, 0.57; 95% CI, 0.41-0.79). Comparatively, patients who were negative for TROP2 per QCS-NMR experienced a median PFS of 2.9 months vs 4.0 months in the respective arms (HR, 1.16; 95% CI, 0.79-1.70).

Study authors concluded that evaluation of TROP2 expression by QCS-NMR could represent the first TROP2 biomarker and the first computational pathology biomarker for predicting response to Dato-DXd in patients with NSCLC. They also noted that the biomarker is being further investigated in frontline advanced NSCLC in the phase 3 AVANZAR (NCT05687266) and TROPION-Lung10 (NCT06357533) studies, in which Dato-DXd is being examined in combination with durvalumab (Imfinzi) plus carboplatin and rilvegostomig, respectively.

Next Wave of TROP2-Targeted Agents Aims to Build on Previous Gains

Beyond Dato-DXd are multiple TROP2-directed ADCs progressing through the development pipeline. The novel TROP2-targeted ADC sacituzumab tirumotecan, which also employs the bystander effect, is being investigated in patients with previously treated recurrent TNBC or mTNBC who experienced disease progression following treatment with at least 2 chemotherapy regimens in the phase 3 OptiTROP-Breast01 trial (NCT05347134). The primary end point of the study is PFS by blinded independent central review (BICR); OS is the key secondary end point.

Findings from the final analysis of OptiTROP-Breast01 presented during the 2024 American Society of Clinical Oncology Annual Meeting showed that patients who received sacituzumab tirumotecan (n = 130) achieved a median PFS by BICR of 6.7 months (95% CI, 5.5-8.0) compared with 2.5 months (95% CI, 1.7-2.7) among those treated with investigator’s choice of chemotherapy (n = 133; HR, 0.32; 95% CI, 0.22-0.44; 

 < .00001). Findings from the interim OS analysis showed that median OS was not yet reached with sacituzumab tirumotecan (95% CI, 11.2-not estimable) vs 9.4 months (95% CI, 8.5-11.7) with chemotherapy.

Sacituzumab tirumotecan monotherapy is being investigated for the frontline treatment of patients with PD-L1–negative TNBC in a phase 3 study (NCT06279364) and in combination with pembrolizumab (Keytruda) for the treatment of patients with early-stage TNBC in the adjuvant setting in the phase 3 MK-2870-012 trial (NCT06393374).

Another novel TROP2-directed ADC, BNT325/DB-1305, received fast track designation from the FDA in January 2024 for the treatment of patients with platinum-resistant ovarian epithelial, fallopian tube, or primary peritoneal cancer following 1 to 3 prior lines of systemic therapy. Preliminary findings from a phase 1/2 study (NCT05438329) supported the decision, demonstrating that patients with advanced solid tumors (n = 23), including NSCLC and TNBC, achieved an ORR of 30.4% and a disease control rate of 87.0%. The 1 patient with fallopian tube cancer experienced an unconfirmed partial response.

“[TROP2-directed ADCs] are moving into first-line metastatic breast cancer [treatment], as well as early[-stage] breast cancer,” Bardia said in conclusion. “There are a number of pivotal studies looking at these drugs, both in the neoadjuvant and adjuvant settings, predominantly for TNBC, and there is also interest in combining these drugs with other agents, particularly immunotherapy. TROP2-directed ADCs appear to be [superior] vs standard chemotherapy, and they’ve changed how we treat [patients with] metastatic breast cancer. In the future, as they move into early[-stage] breast cancer, the question will be [a matter of weighing] the efficacy and the toxicity profile [of these agents] in a curative setting.”

FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. Updated April 8, 2021. Accessed September 6, 2024. bit.ly/4d2gIrc

Okajima D, Yasuda S, Maejima T, et al. Datopotamab deruxtecan, a novel TROP2-directed antibody-drug conjugate, demonstrates potent antitumor activity by efficient drug delivery to tumor cells. 

. 2021;20(12):2329-2340. doi:10.1158/1535-7163.MCT-21-0206

Zaman S, Jadid H, Denson AC, Gray JE. Targeting Trop-2 in solid tumors: future prospects. 

. 2019;12:1781-1790. doi:10.2147/OTT.S162447

FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. FDA. April 13, 2021. Accessed September 6, 2024. bit.ly/4cYgP72

FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. FDA. February 3, 2023. Accessed September 6, 2024. bit.ly/4d9l5R8

Bardia A, Krop IE, Kogawa T, et al. Datopotamab deruxtecan in advanced or metastatic HR+/HER2– and triple-negative breast cancer: results from the phase I TROPION-PanTumor01 study. 

. 2024;42(19):2281-2294. doi:10.1200/JCO.23.01909

Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC)

 primary results from the randomised phase III TROPION-Breast01 trial. 

. 2023;34(suppl 2):S1264-S1265. doi:10.1016/j.annonc.2023.10.015

Datopotamab deruxtecan biologics license application accepted in the U.S. for patients with previously treated metastatic HR positive, HER2 negative breast cancer. News release. Daiichi Sankyo. April 2, 2024. Accessed September 11, 2024. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202404/20240402_E.pdf

Sands J, Lisberg A, Okamoto I, et al. Datopotamab deruxtecan vs docetaxel in patients with non-small cell lung cancer: final overall survival from TROPIONLung01. Abstract presented at: International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract 2640.

Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed September 11, 2024. bit.ly/4e5Clbh

Garassino MC, Sands J, Paz-Ares L, et al. Normalized membrane ratio of TROP2 by quantitative continuous scoring is predictive of clinical outcomes in TROPION-Lung01. Abstract presented at: International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract 4037.

Xu B, Yin Y, Fan Y, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): results from the phase III OptiTROP-Breast01 study. 

. 2024;42(suppl 16):104. doi:10.1200/JCO.2024.42.16_suppl.104

BioNTech and DualityBio receive FDA fast track designation for next-generation antibody-drug conjugate candidate BNT325/DB-1305. News release. BioNTech SE. January 31, 2024. Accessed September 11, 2024. bit.ly/3XHuDOE

Marathe O, Cheng Y, Spira AI, et al. DB-1305 (a Trop-2 targeted antibody-drug-conjugate [ADC]) in patients (pts) with advanced solid tumors: preliminary clinical results from the phase (Ph) I/IIa study. 

. 2023;34(suppl 2):S480. doi:10.1016/j.annonc.2023.09.1875

TROP2-targeted antibody-drug conjugates (ADCs) are gaining traction in oncology, particularly for breast and lung cancers, due to their promising safety and efficacy profiles. Sacituzumab govitecan, the first FDA-approved TROP2-directed ADC, has shown effectiveness in various cancer types. Datopotamab deruxtecan (Dato-DXd) is another promising TROP2-targeted ADC, demonstrating significant clinical activity and a favorable safety profile in ongoing trials. The development pipeline includes additional TROP2-directed ADCs, such as sacituzumab tirumotecan and BNT325/DB-1305, which are being evaluated for their potential in treating various solid tumors.

Pathways

Ian Krop, MD, PhD, and Aditya Bardia, MD, MPH, FASCO, detail how TROP2-directed ADCs have generated excitement in breast cancer and other solid tumors. 

TROP2 Offers Attractive Therapeutic Target in Breast Cancer and Other Solid Tumors

As a durvalumab (Imfinzi) regimen joins the pembrolizumab (Keytruda) combination in the perioperative treatment paradigm for patients with resectable non–small cell lung cancer (NSCLC), combination therapies with neoadjuvant immune checkpoint inhibitors (ICIs) and chemotherapy followed by an adjuvant ICI have shown that they’re here to stay.

“I urge physicians to [give] patients with earlystage lung cancers who are candidates for surgery [checkpoint inhibitors plus chemotherapy] whenever possible; if they don’t have 

 [alterations], those patients need a checkpoint inhibitor and chemotherapy presurgery. You have the best chance to make a huge impact in patients’ [lives with that approach],” Mark G. Kris, MD, said in an interview with 

The August 15, 2024, addition of neoadjuvant durvalumab plus platinum-based chemotherapy followed by adjuvant durvalumab monotherapy to the treatment paradigm for adult patients with resectable NSCLC and no 

 alterations represents one of the most recent advancements in the perioperative setting.

Treatment with the PD-L1 checkpoint inhibitor regimen reduced the risk of disease progression, recurrence, or death by 32% vs neoadjuvant platinum-based chemotherapy plus placebo followed by adjuvant placebo in this patient population. The median event-free survival (EFS) was not reached (NR; 95% CI, 31.9-NR) in patients who received the durvalumab regimen (n = 366) vs 25.9 months (95% CI, 18.9-NR) in those who received the placebo regimen (n = 374; HR, 0.68; 95% CI, 0.53-0.88; 

 = .0039). Additional data from the pivotal phase 3 AEGEAN trial (NCT03800134) revealed that the pathologic complete response (pCR) rate was 17.2% (95% CI, 13.5%-21.5%) compared with 4.3% (95% CI, 2.5%- 6.8%), respectively (

Several Chemoimmunotherapy Strategies Prove Effective

“In the perioperative space, it is unexpected and amazing how effective checkpoint inhibitors are [when] given before surgery. I don’t think anybody would have suspected that, and it’s been shown [many times],” Kris explained. Kris is a thoracic medical oncologist and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York, New York.

Findings from the phase 3 CheckMate 77T study (NCT04025879) also demonstrated an improvement with the addition of a checkpoint inhibitor—nivolumab (Opdivo)—to chemotherapy (n = 229) for patients with resectable NSCLC, significantly extending EFS vs chemotherapy alone (n = 232; HR, 0.58; 97.36% CI, 0.42-0.81; 

 < .001). The pCR rate also improved at 25.3% vs 4.7%, respectively (OR, 6.64; 95% CI, 3.40-12.97).

Kris added, “It is unusual that there would be 8 randomized trials all over the world that reach the same conclusion that immunotherapy [given] preoperatively with chemotherapy is better than chemotherapy alone. [But the data from those trials have shown it is well] tolerated and sometimes yields great results, including the complete eradication of the cancer, something we don’t see with other approaches.”

One of those 8 trials is the phase 3 KEYNOTE-671 trial (NCT03425643). Data from the study led to the FDA approval of neoadjuvant pembrolizumab plus platinum-containing chemotherapy, followed by single-agent adjuvant pembrolizumab for patients with resectable NSCLC.

 At a median follow-up of 29.8 months (range, 0.4-62.0), the pembrolizumab regimen significantly improved overall survival (OS) vs placebo plus chemotherapy followed by adjuvant placebo, reducing the risk of death by 28% (HR, 0.72; 95% CI, 0.56-0.93; 1-sided 

Although findings from KEYNOTE-671 were from 1 of the 8 randomized clinical trials that demonstrated a significant benefit from combined neoadjuvant chemoimmunotherapy in this patient population, KEYNOTE-671 was the only trial of the 8 where OS was one of the primary end points, according to a systematic review and meta-analysis. Further, data from KEYNOTE-671 confirmed significant prolongation of OS for patients treated with 4 cycles of neoadjuvant pembrolizumab plus cisplatin-based chemotherapy followed by 9 months of adjuvant pembrolizumab.

The systematic review and meta-analysis examined data from the 8 trials in patients with early-stage NSCLC who received neoadjuvant ICIs and chemotherapy; findings also revealed that the improved pCR and EFS rates seen were not significantly modified by main patient characteristics or tumor- or treatment-related factors, including PD-L1 status.

Considerations With Checkpoint Inhibition From Surgery to Oligoprogression

In regard to tolerability when adding an ICI to chemotherapy, overall treatment-related adverse effects (TRAEs) in CheckMate 77T occurred at any grade in 89.0% of patients who received the nivolumab regimen and 87.0% of those who received the chemotherapy/placebo regimen. These events led to treatment discontinuation in 19.3% vs 7.4% of patients, respectively, and 2 patients in the nivolumab group died due to TRAEs in the neoadjuvant period.

In AEGEAN, serious AEs occurred in 37.7% of patients receiving the durvalumab regimen compared with 31.4% of patients receiving the chemotherapy/placebo regimen. They led to discontinuation in 12.0% vs 6.0% of patients, respectively, and 5.7% compared with 3.8% of patients died due to AEs, respectively.

Furthermore, Kris noted that a newer treatment consideration with ICIs concerns patients who experience oligoprogression. “The concept of treatment beyond progression goes against everything I was taught. [I was taught if a] patient progresses, you have to change therapy. Particularly with targeted therapies, you have situations where there’s millimeter growth over many years and it’s in the patient’s best interest to keep them on the drug, even in the face of progression,” Kris said.

He added that when “you have patients with long disease-free survival, the concept of oligoprogression [is important]. There is growing literature that after [a patient] has a good result with systemic therapy, persisting disease sites in both small cell lung cancer and NSCLC could benefit from a local, targeted therapy, [specifically] with checkpoint inhibition; if a [patient] has single sites of progression, using a local therapy for those single sites even in the face of progression, particularly in the liver, can get a patient back into a disease control state. That’s thinking that we don’t normally have.”

Experts Detail Factors for These Treatment Strategies and More

With new therapies and an array of options opening the door for additional questions surrounding optimal treatments in NSCLC, the 

, hosted by Physicians’ Education Resource

, LLC, will serve as an opportunity to have key questions answered (

). The conference, which will take place on November 16, 2024, in New York, New York, will parse through the latest data and feature multidisciplinary panel discussions in a tumor board format.

“We make sure that [each] presentation is not just a dry data review—there is a bottom line there, synthesizing the data and saying with what we know today about this area of question or controversy, this is what I think is best. If clinicians come to the New York Lung Cancers Symposium, they’re going to walk away with the expert’s true opinion, and not just a list of possibilities,” said Kris, who is cochair of the meeting with Balazs Halmos, MD, MS, associate director of Clinical Science at Montefiore Einstein Comprehensive Cancer Center in the Bronx, New York.

Kris and colleagues from the tristate area will gather in the city to discuss the perioperative setting and more, homing in on genomic testing strategies and best practices, multidisciplinary considerations in treatment, and approaches to mitigate as well as manage treatment-related toxicities.

“There’s been a huge output of information on how to treat patients with early-stage [disease], particularly those in the perioperative [setting]. A large amount of data on neoadjuvant therapy [have come out, with] a consensus that wherever it’s feasible it should be done and [is more efficacious],” Kris said. “The perioperative space is a big one right now.”

FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer. FDA. August 15, 2024. Accessed August 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer

Imfinzi. Prescribing information. AstraZeneca; 2024. Accessed August 21, 2024. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/9496217c-08b3-432b-ab4f-538d795820bd/9496217c-08b3-432b-ab4f-538d795820bd_viewable_rendition__v.pdf

Cascone T, Awad MM, Spicer JD, et al; CheckMate 77T Investigators. Perioperative nivolumab in resectable lung cancer. 

. 2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926

FDA approves neoadjuvant/ adjuvant pembrolizumab for resectable non-small cell lung cancer. FDA. October 16, 2023. Accessed August 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-adjuvant-pembrolizumab-resectable-non-small-cell-lung-cancer

European Commission approves Merck’s Keytruda (pembrolizumab) plus chemotherapy as neoadjuvant treatment, then continued as monotherapy as adjuvant treatment, for resectable non-small cell lung cancer (NSCLC) at high risk of recurrence in adults. News release. Merck. March 28, 2024. Accessed August 21, 2024. https://www.merck.com/news/european-commission-approves-mercks-keytruda-pembrolizumab-plus-chemotherapy-as-neoadjuvant-treatment-then-continued-as-monotherapy-as-adjuvant-treatment-for-resectable-non-small-ce/

Banna GL, Hassan MA, Signori A, et al. Neoadjuvant chemo-immunotherapy for early-stage non-small cell lung cancer: a systematic review and meta-analysis. 

. 2024;7(4):e246837. doi:10.1001/jamanetworkopen.2024.6837

Heymach JV, Harpole D, Mitsudomi T, et al; AEGEAN Investigators. Perioperative durvalumab for resectable non-small-cell lung cancer. 

. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875

 New York Lung Cancers Symposium. Physicians’ Education Resource, LLC. Accessed August 21, 2024. https://www.gotoper.com/courses/new-york-lung-cancers-symposium?utm_medium=paid&utm_source=google&utm_campaign=nyl_24_&gad_source=1&gclid=EAIaIQobChMI4qO8gu-DiAMVjzMIBR0S-gt8EAAYASAAEgI6UvD_BwE

The integration of durvalumab and pembrolizumab regimens into the perioperative treatment of resectable NSCLC marks a significant advancement, emphasizing the efficacy of combining neoadjuvant ICIs with chemotherapy. Recent trials, including AEGEAN and CheckMate 77T, demonstrate improved event-free survival and pathologic complete response rates with these combinations. Despite the benefits, treatment-related adverse effects remain a concern. The concept of oligoprogression challenges traditional treatment paradigms, suggesting potential benefits from local therapies. Upcoming discussions at the New York Lung Cancers Symposium will address these evolving strategies and their implications.

Cover Story

Combination therapies with neoadjuvant ICIs and chemotherapy followed by an adjuvant ICI are here to stay in resectable non–small cell lung cancer.

Chemoimmunotherapy Is at the Forefront of the Perioperative NSCLC Paradigm

New combination regimens for patients with metastatic colorectal cancer (mCRC) who have experienced disease progression after frontline therapy are emerging that include tyrosine kinase inhibitors (TKIs), EGFR and VEGF inhibitors, and novel agents as components, expanding the treatment arsenal for clinicians beyond traditional chemotherapy-based approaches. Thus, an emphasis on molecular testing is needed to sift through these options in the second and third lines of therapy.

“We say ‘first, second, and third line,’ but treatment [today] for CRC is more of a continuum, and there’s not a one-size-fits-all approach,” Kristen K. Ciombor, MD, MSCI, said. “There are ways to personalize therapy, not only molecularly, but also based on tumor burden and patient performance status, goals, and preferences; we have to take all…those things into consideration. Getting molecular status early on is important because it used to be that we had [more] time to get these data, and now we’re making firstand second-line treatment decisions based on [them]. We have more and more treatment options that are biomarker selected in the second line after initial chemotherapy. It’s important to get those data early on so that you can counsel your patients [on] the best options.”

, a panel of expert clinicians in the CRC field discussed recent findings from pivotal clinical trials that were primarily shared during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. In the second-line setting, the panelists discussed findings from studies including the phase 3 CodeBreaK300 trial (NCT05198934) and the phase 2 MOUNTAINEER study (NCT03043313), which examined sotorasib (Lumakras) and tucatinib (Tukysa) plus trastuzumab (Herceptin), respectively. Then they highlighted regimens in the third line and beyond, such as regorafenib (Stivarga), trifluridine/tipiracil (Lonsurf; TAS-102) with or without bevacizumab (Avastin), and fruquintinib (Fruzaqla).

Second-Line Options Rapidly Expand With an Emphasis on Personalization

During the 2024 ASCO Annual Meeting, investigators presented findings from the overall survival (OS) analysis of CodeBreaK300. This multicenter, open-label trial examined the KRAS G12C inhibitor sotorasib at a daily dose of either 960 mg (n = 53) or 240 mg (n = 53) in combination with the EGFR inhibitor panitumumab (Vectibix) vs investigator’s choice of standard-of-care trifluridine/tipiracil or regorafenib in patients with 

 G12C–mutated metastatic CRC (mCRC) who had not received a prior KRAS G12C inhibitor. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); OS and overall response rate (ORR) represented key secondary end points.

Updated findings showed that the median PFS in the sotorasib 960-mg arm was 5.8 months (95% CI, 4.2-7.5), and 4.0 months (95% CI, 3.7-5.9) in the sotorasib 240-mg arm, conferring respective 54% (HR, 0.46; 95% CI, 0.29-0.72) and 43% (HR, 0.57; 95% CI, 0.37-0.88) reductions in the risk of disease progression or death compared with the investigator’s choice arm (n = 54), which delivered a median PFS of 2.0 months (95% CI, 1.9-3.9). Additionally, at a median follow-up of 13.6 months, patients in both the sotorasib 960-mg arm (HR, 0.70; 95% CI, 0.41-1.18; 2-sided 

 = .20) and 240-mg arm (HR, 0.83; 95% CI, 0.49-1.39; 2-sided 

 = .50) experienced a trend toward an OS benefit vs the control arm.

In their conclusion, the study authors advocated for sotorasib at the 960-mg daily dose level in combination with panitumumab as the new SOC therapy for patients with chemotherapy-refractory 

“The improvement in OS was not statistically significant, but that’s to be expected, given that this [study] was not powered for OS,” Marwan G. Fakih, MD, who presented the CodeBreaK300 data during the meeting, explained. “One thing we learned is that the ORR went up a little bit from the last report. The ORR was 30.0% [95% CI, 18.3%-44.3%] for sotorasib 960 mg plus panitumumab, and the responses are durable. The duration of response [DOR] was 10.1 months [95% CI, 3.1-12.9+] with sotorasib 960 mg plus panitumumab. [These are] exciting data [in] refractory disease, and hopefully [this regimen is] an option for patients with a 

 G12C mutation who progressed on prior systemic chemotherapy.”

 mutation, don’t just close it up and say, ‘I have [a patient with] a 

 mutation it is and note that because you now have access to KRAS G12C inhibitors in this population,” John Marshall, MD, added.

For patients without the mutation, those with 

 wild-type, HER2-positive unresectable CRC or mCRC, tucatinib plus trastuzumab is available. The combination received accelerated approval in the setting following disease progression with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in January 2023. During the 2024 ASCO Annual Meeting, investigators presented results from the final analysis of MOUNTAINEER, which supported the 2023 regulatory decision.

At a median follow-up of 32.4 months, patients who received the combination (n = 84) achieved a confirmed ORR of 39.3% (95% CI, 28.8%-50.5%), with a median DOR of 15.2 months (95% CI, 8.9-20.5). The median PFS and OS were 8.1 months (95% CI, 4.2-10.2) and 23.9 months (95% CI, 18.7-28.3), respectively.

“The regimen remains active, and it’s been fully incorporated into National Comprehensive Cancer Network guidelines, [including] for initial therapy if you’re concerned about [the] tolerability of combination chemotherapy, because this regimen is quite well tolerated,” Al B. Benson III, MD, FACP, FACCC, FASCO, noted. “Some of the principal adverse effects [AEs] include fatigue, diarrhea, and nausea, as well as hypertension, as one would imagine with a TKI. Overall, it’s well tolerated, and its principal indication is for subsequent therapy along with the other HER2-targeted drugs. [We now have] multiple regimens to choose from in this population.”

To conclude their discussion of second-line treatment options, the panelists spotlighted 2 Chinese studies examining novel combination regimens, the phase 2 ZL-IRIAN study (NCT05229003) and another phase 2 study (ChiCTR2200059280). ZL-IRIAN evaluated irinotecan plus the novel TKI anlotinib with or without the PD-1 inhibitor penpulimab in patients with recurrent or metastatic BRAF wildtype colorectal adenocarcinoma. The other phase 2 study evaluated the VEGF inhibitor fruquintinib (Fruzaqla) in combination with investigator’s choice of chemotherapy, followed by maintenance therapy with fruquintinib.

In ZL-IRIAN, patients with mismatch repair– proficient (pMMR)/microsatellite stable (MSS) mCRC who received the doublet (n = 23) achieved an ORR of 39.1% and a disease control rate (DCR) of 87.0%. The median PFS was 9.57 months (95% CI, 25.69-66.99); the 6- and 12-month PFS rates were 72.44% and 37.19%, respectively.

In the triplet arm (n = 21), which did not require pMMR/MSS status, the ORR was 38.1%, and the DCR was 90.5%. The median PFS was not reached; the 6- and 12-month PFS rates were 74.06% and 53.46%, respectively.

“This [trial’s evidence] shows that we’re still trying to move the needle, and that should be the constant pursuit here because we have not yet figured everything out,” Stacey Cohen, MD, commented. “[The ZL-IRIAN regimen] is an interesting combination using a mild chemotherapy backbone in MSS patients. It’s an interesting trial, [but] to me, it was more thought-provoking than practice changing at this point. The problem is that we don’t know how many of these patients had prior bevacizumab, and we don’t know if this is [superior to] full FOLFIRI [leucovorin calcium, fluorouracil (5-FU), and irinotecan] plus bevacizumab or FOLFIRI alone.”

In the other phase 2 study, which also examined patients with a pMMR/MSS phenotype, efficacyevaluable patients (n = 96) achieved a median PFS and OS of 6.9 months (95% CI, 5.2-8.6) and 20.1 months (95% CI, 13.7-26.3), respectively, at a median follow-up of 9.3 months. Additionally, the ORR among these patients was 26.0% (95% CI, 17.9%- 36.2%), with a median DOR of 11.3 months (95% CI, 8.6-14.0).

“The toxicity profile looked similar to what we would expect with these drugs as we get to use them more in different lines of therapy,” Ciombor said. “[This regimen] doesn’t seem to be significantly better efficacy-wise [than other options], but what I wonder [is whether] it would be preferable for patients to [receive] fruquintinib maintenance as opposed to 5-FU plus bevacizumab maintenance. [However], one has to consider not just toxicity and efficacy, but financial toxicity as well, as it’s a more expensive drug.”

Multiple Regimens Display Promise in the Third Line and Beyond

As of May 2024, there are 4 FDA-approved treatment regimens for patients needing third- or later-line treatment: regorafenib, trifluridine/ tipiracil with or without bevacizumab, and fruquintinib. However, data regarding how to properly sequence these options are still emerging.

“By the third line and beyond, patients [have received a good deal of treatment],” Ciombor said. “Patients sometimes are having cancer complications and certainly having chemotherapy complications at this point. They may be having more symptoms from increasing tumor burden and residual effects from prior chemotherapy, [such as] cytopenias, neuropathy, and diarrhea. All…those [factors] play a role in how we decide [on] and sequence further therapies.”

One notable study that enrolled patients with mCRC in the third line of treatment and beyond was the phase 3 SUNLIGHT trial (NCT04737187). SUNLIGHT evaluated trifluridine/ tipiracil with and without bevacizumab in patients who experienced disease progression following treatment with a maximum of 2 prior chemotherapy-based regimens. Data from SUNLIGHT supported the August 2023 FDA approval of trifluridine/ tipiracil plus bevacizumab in patients with mCRC who previously received fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF agent, and, if they had 

Findings from the primary analysis of SUNLIGHT demonstrated that patients in the combination arm (n = 246) experienced a median OS of 10.8 months (95% CI, 9.4-11.8) compared with 7.5 months (95% CI, 6.3-8.6) among those treated with trifluridine/tipiracil alone (HR, 0.61; 95% CI, 0.49-0.77; 

 < .001). The median PFS was 5.6 months (95% CI, 4.5-5.9) vs 2.4 months (95% CI, 2.1-3.2), respectively.

During the 2024 Gastrointestinal Cancers Symposium (ASCO GI) and the 2024 ASCO Annual Meeting, multiple abstracts were presented that aimed to further define the role of the SUNLIGHT regimen based on the characteristics of patient subgroups.

At the ASCO GI meeting, Fakih and coauthors presented findings from a subgroup analysis that examined the effect of trifluridine/tipiracil in combination with bevacizumab vs trifluridine/ tipiracil alone in patients younger than 65 years, patients aged 65 to 74 years, and those of at least 75 years of age. The hazard ratios for OS were 0.65 (95% CI, 0.48-0.87), 0.64 (95% CI, 0.43-0.94), and 0.49 (95% CI, 0.27-0.90), respectively, all of which were in favor of the combination arm.

“The hazard ratio is almost the same for all the subgroups; it didn’t matter if [the patient was] younger or older. [However] there were a few more AEs for the group of patients who were 65 to 74 [years of age],” Fakih said. “It was difficult to [arrive at] a conclusive answer regarding safety for such a small group. The take-home message is if the patient is fit, and satisfied the criteria for inclusion on SUNLIGHT, they benefited, irrespective of the age group.”

Then, during the 2024 ASCO Annual Meeting, investigators presented results from another analysis of SUNLIGHT that aimed to determine the effect of colorectal liver metastases on the efficacy of trifluridine/tipiracil with or without bevacizumab. Patients with colorectal liver metastases who received the combination (n = 194) experienced a benefit in OS (HR, 0.61; 95% CI, 0.48-0.77; 

 < .001) and PFS (HR, 0.44; 95% CI, 0.35-0.55; 

 < .001) compared with those who received trifluridine/tipiracil alone (n = 188). Patients without colorectal liver metastases experienced a similar OS (HR, 0.60; 95% CI, 0.35-1.0; 

= .052) and PFS (HR, 0.38; 95% CI, 0.24-0.58; 

 < .001) benefit with the combination (n = 52) vs trifluridine/tipiracil monotherapy (n = 58).

“In SUNLIGHT, the individuals with liver metastases did do somewhat less well, and that may simply be a prognostic factor,” Benson explained. “However, it did appear across the board that patients did benefit with the addition of bevacizumab compared with trifluridine/ tipiracil alone. At least with this regimen, I believe it’s still fine to offer [patients] trifluridine/ tipiracil and bevacizumab; they may not do as well overall, but it’s what we might expect when [these patients] have a poor prognosis.”

Investigators also examined fruquintinib in combination with best supportive care in the third line and beyond in the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) trials. In the Chinese FRESCO study, patients with mCRC who received fruquintinib (n = 278) following disease progression after at least 2 standard chemotherapy regimens achieved a median OS of 9.3 months (95% CI, 8.18-10.45) vs 6.57 months (95% CI, 5.88-8.11) among those who received placebo (n = 138; HR, 0.65; 95% CI, 0.51-0.83; 

 < .001). Building on these findings, the global FRESCO-2 trial enrolled patients with mCRC who had exhausted all standard cytotoxic and targeted treatment options and experienced disease progression on or were intolerant to trifluridine/tipiracil and/or regorafenib. Patients who received fruquintinib (n = 461) achieved a median OS of 7.4 months (95% CI, 6.7-8.2) compared with 4.8 months (95% CI, 4.0-5.8) in the placebo arm (n = 230; HR, 0.66; 95% CI, 0.55-0.80; 

“[FRESCO and FRESCO-2] are different patient populations,” Ciombor commented. “The FDA approved fruquintinib in mCRC in the third line and beyond, which gives us some options. I typically use trifluridine/tipiracil and bevacizumab prior to fruquintinib, with the exception being possibly in patients who have cytopenias who need to recover.”

During the ASCO 2024 meeting, investigators presented findings from a pooled analysis of FRESCO and FRESCO-2 that examined the effect of prior treatment sequences in the refractory setting. Patients in both studies who received prior trifluridine/tipiracil then regorafenib (HR, 0.532; 95% CI, 0.353-0.802), prior regorafenib then trifluridine/tipiracil (HR, 0.666; 95% CI, 0.432-1.025), prior trifluridine/tipiracil only (HR, 0.723; 95% CI, 0.557-0.938), and prior regorafenib only (HR, 0.772; 95% CI, 0.379-1.573) and patients who did not receive prior trifluridine/tipiracil or regorafenib (HR, 0.652; 95% CI, 0.512-0.829) all experienced an OS benefit with fruquintinib vs placebo. Patients in these subgroups also experienced a PFS benefit with fruquintinib, with respective hazard ratios of 0.313 (95% CI, 0.210- 0.467), 0.262 (95% CI, 0.161-0.396), 0.367 (95% CI, 0.287-0.470), 0.292 (95% CI, 0.139-0.611), and 0.262 (95% CI, 0.205-0.336).

“We saw [additional] data out of ASCO [2024] about possibly the only potential role for regorafenib in the larger space, and that’s in what we call ‘regorafenib plus,’” Ciombor added. “Whether in combination with immune-oncology therapy or locoregional approaches, I believe it still deserves potential exploration. But as monotherapy, it has a limited role at this point.”

Fakih M, Salvatore L, Esaki T, et al. Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for 

 G12C-mutated metastatic colorectal cancer (mCRC). 

. 2024;42(suppl 17):LBA3510. doi:10.1200/ JCO.2024.42.17_suppl.LBA3510

FDA grants accelerated approval to tucatinib with trastuzumab for colorectal cancer. FDA. January 19, 2023. Accessed August 28, 2024. https://www.fda.gov/drugs/resources-informationapproved- drugs/fda-grants-accelerated-approval-tucatinibtrastuzumab- colorectal-cancer

Strickler JH, Cercek A, Siena S, et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). 

. 2024;42(suppl 16):3509. doi:10.1200/JCO.2024.42.16_suppl.3509

Wang C, Li W, Zhu X, Geng Q, Zhao X, Guo W. Irinotecan plus anlotinib or further in combination with penpulimab as secondline treatment of metastatic colorectal cancer (ZL-IRIAN). 

. 2024;42(suppl 16):3570. doi:10.1200/JCO.2024.42.16_ suppl.3570

Zhao W, Li J, Li L, et al. Efficacy and safety of fruquintinib plus investigator’s choice of chemotherapy as second-line therapy in metastatic colorectal cancer: updated results of a multicenter, single-arm, phase 2 trial. 

. 2024;42(suppl 16):3571. doi:10.1200/JCO.2024.42.16_suppl.3571

Barzi A, Bekaii-Saab T. Sequencing considerations in the thirdline treatment of metastatic colorectal cancer. 

. 2024;30(suppl 2):S31-S35. doi:10.37765/ajmc.2024.89546

Prager GW, Taieb J, Fakih M, et al; SUNLIGHT Investigators. Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. 

. 2023;388(18):1657-1667. doi:10.1056/NEJMoa2214963

A panel of clinicians in the CRC field discussed findings from pivotal clinical trials that were primarily shared during the 2024 ASCO Annual Meeting. 

Vol. 25/No. 12 | Oncology Live®

McKesson's Patient-Reported Outcomes Measure Will Track Improvements in Health-Related Social Needs

TROP2 Offers Attractive Therapeutic Target in Breast Cancer and Other Solid Tumors

Chemoimmunotherapy Is at the Forefront of the Perioperative NSCLC Paradigm

Treatment Personalization Is Poised to Define New Era of mCRC Therapy

Molecularly Targeted Therapeutics Are Precisely Aimed

Medicare Drug Price Negotiations Will Have Domino Effect for Community Oncology Practices