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As the field of breast cancer continues to rapidly evolve and shift with new therapies shaking up the paradigm, the 22nd Annual International Congress on the Future of Breast Cancer® (IBC) East and West conferences give clinicians the chance to debate treatments and ask pressing questions, according to the chair Joyce A. O’Shaughnessy, MD. IBC East is scheduled for July 14 to 15, and IBC West from July 28 to 29, 2023. 

“Probably the biggest story in the past year is HER2-low being called out as a therapeutic subset of opportunity. We don’t think it’s a different biologic subset, but it certainly is a different therapeutic subset,” said O’Shaughnessy, who is the Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center and Director of the Breast Cancer Research Program at Texas Oncology, US Oncology in Dallas, Texas.

O’Shaughnessy also looks forward to the debates among colleagues across specialties at the meetings. “Not surprisingly, the surgeons don’t always agree with the radiation oncologist in terms of approach. I like to hear a difference of opinion and that’s what’s valuable for me: hearing it again in the context and then hearing it vetted so I can see how others feel this should be applied to practice.” 

In addition to highlighting multidisciplinary approaches including discussions on tumor boards, O’Shaughnessy discussed how to better assist patients with accessing care, and notable advances in the field particularly with the HER2 classification.

How have the IBC conferences evolved over the years? 

The IBC East and West are important multidisciplinary congresses aimed at bringing [the audiences] up to speed on new data, as well as vetting that data and figuring out how to integrate it into our practices. Breast cancer is not just medical oncology; locoregional care has a huge impact not only on locoregional control, but also without evidence of disease it can favorably impact distant recurrence as well. The locoregional issues are very rapidly evolving and there are new studies coming out for escalation and de-escalation strategies for surgical intervention and radiation. This is a constantly moving [target with] lots of global trials as well as with systemic approaches and risk reduction approaches and survivorship issues. 

Of course, we have our national guidelines, but there are always nuances and it’s up to us to apply these new data and the guidelines to individual patients. You have to know the data and you have to have heard the new data discussed and debated— that’s the purpose of IBC East and West over the past 20-plus years since the congress has been in existence. The sheer volume of data has done nothing but get larger for example, novel diagnostics, liquid biopsies, next-generation sequencing, these simply didn’t exist 20-plus years ago. There’s increasing focus on multidisciplinary care in our institutions, and therefore at our meetings too.

What key takeaways do you hope congress attendees will leave with? 

I love the data, I love the science, and I benefit from hearing the data presented by expert faculty who have, importantly, put it in[to] context with existing data. 

I hope the attendees go back truly [thinking], “Oh, wow, I didn’t know that. I have to bring that to the clinic Monday morning.” We all have those “aha” moments when we go to and listen to our expert colleagues and see what they’re doing and [realize,] “I’m not doing that.” Those are the things that I get out of these congresses and that’s what I hope my colleagues will get out of [them].

What is the role of multidisciplinary care in breast cancer and how is it important for patients? 

As I tell my patients, breast cancer management is always 2 parts. We must take optimal care of the locoregional area, the breast itself, and the surrounding lymph node beds. We have to get control of disease; you never want to see it back again. We also have restoration [and] reconstruction. Not every patient needs that, but that’s very important for overall well-being [and also] critically important for breast cancer control. 

And then you need to have systemic management. There are still multidisciplinary issues around who could benefit from surgical management of the primary tumor, or which patients benefit from radiation management of the primary [tumor], as well as palliative radiation approaches or surgical approaches for the patient with metastatic disease. We always have the dual goals—locoregional management or management of a particularly morbid sight of metastatic disease, and general systemic management. Breast cancer is both at once.

[Multidisciplinary care begins when] patients usually see [the] surgical oncology and medical oncology [departments] immediately after diagnosis, particularly if they have stage II or III disease. Patients with stage I disease may begin with the surgeon and then [we] bring the medical oncologist [and] radiation oncologist in if the patient needs to go to surgery first. Otherwise, the surgeon will reach out to the radiation oncologist and the medical oncologist to get their consultation sooner [rather] than later. Of course, we have our tumor boards; most of us have weekly tumor boards where we will have a multidisciplinary discussion of either all patients or controversial patients where you hear different options [about] what we should do [and] what the team think[s] is the best approach for this patient. 

What are typical multidisciplinary discussions that take place during the tumor boards? 

The tumor boards are generally focused on early-stage breast cancer. The multidisciplinary work is most intensive in the early-stage breast cancer where patients are almost always going to get systemic therapy; they will get surgery almost always, and very often will get radiation therapy. You need breast imagers [and] pathologists. 

In the metastatic setting, patients and medical oncologists get to know each other very well for many years. Generally speaking, most of the treatment there is systemic. There are issues in a subset of patients regarding control of the primary breast cancer and that means surgery and/or radiation therapy, or palliation of symptoms. Now there’s the new concept of oligometastasis or oligoprogression where patients have metastatic disease but it’s very small volume. How do you bring multidisciplinary care to the patient with oligometastatic or oligoprogressive disease? Through multidisciplinary care. Those are excellent patient [cases] to present at multidisciplinary tumor conferences as well.

What recent or notable changes have affected the standards of care across breast cancer? 

Fortunately, [regarding HER2-low disease] it’s easy [to implement changes] because patients always have HER2 immunohistochemistry [(IHC) testing] done. We didn’t have to come up with a new diagnostic tool. But HER2-low [disease] is IHC 1+ or 2 expression by IHC and [fluorescence in situ hybridization] negative. We have a lot of those patients; it’s two-thirds of hormone receptor–positive, HER2-negative patients and it’s approximately one-third of triple-negative patients. It is by far the biggest subset of patients we have and it’s bigger than [the one with] hormone receptor–positive, HER2-negative [disease], which has always been our biggest group. 

Right now, [HER2-low status is] only relevant in the metastatic setting; you have to have a therapeutic to make a diagnostic relevant and we have the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki [Enhertu]. Trastuzumab [Herceptin] we’re all extremely familiar with, [and] we’ve had [ado-trastuzumab emtansine (Kadcyla)] T-DM1 for many years. Now we have trastuzumab deruxtecan with a different payload of a topoisomerase 1 inhibitor payload, but it’s a new option for patients and the key is that patients with hormone receptor–positive breast cancer still need to get optimal endocrine therapy. 

Unfortunately, the cancer [eventually] becomes resistant to endocrine therapy [and] you have to go onto cytotoxic therapy. A lot of times we’ll use oral capecitabine, which is a very well-tolerated medication;, it’s a chemotherapy, a cytotoxic, [and there is] no alopecia [and] it doesn’t cause immunosuppression. Then we have to go to [intravenous] IV cytotoxic therapy and heretofore, we’ve only had 3 cytotoxic agents [and they] were more toxic because the cytotoxic agents are not bound to an antibody, which is [designed to be] more targeted and directed.

In the second line we will use trastuzumab deruxtecan for patients with HER2-low [disease] and this is a big advance. It’s very highly effective, it’s way more effective than single-agent chemotherapy, but it’s also less toxic in general in terms of how patients feel. You do have to watch out for interstitial lung disease. There’s a management surveillance strategy around interstitial lung disease because it’s very serious if it isn’t caught and treated early. But that aside, it’s more effective than anything we have for these patients in the second-line setting and it’s also very well tolerated [with] quite durable responses. 

This is major now that trastuzumab deruxtecan has also been moved up into the adjuvant and neoadjuvant settings; it’s being brought into early[-stage] breast cancer. Of course, in HER2-positive breast cancer it’s been in clinical trials both preoperatively and in the adjuvant setting, but in HER2-low [disease] it’s also being evaluated as a substitute for chemotherapy or as an add-on for patients who need additional therapies in the curative setting.

Articles

Joyce A. O’Shaughnessy, MD, highlights multidisciplinary approaches including discussions on tumor boards, and discusses how to better assist patients with accessing care, and notable advances in the field particularly with the HER2 classification.

O’Shaughnessy Showcases Highlights in  Breast Cancer Guiding 2023 IBC Congresses

Patients with hematologic malignancies often experience high costs during treatment and require a caregiver. To evaluate the prevalence of financial toxicity and observe the effect of 

Coverage and Cost-of-Care Links (CC Links)

, a program providing financial navigation, investigators initiated a nonrandomized study (NCT05465577).

Financial navigation is “a comprehensive program where we’re screening for financial toxicity [and] helping the patient and the caregiver get connected with resources,” according to Jean Edward, PhD, RN, CHPE. “That sometimes involves helping them [to] find the right insurance plan, understand the insurance, understand the cost of care, and make calls on their behalf if they need to like a liaison at times and following up on those things.” Edward is an associate professor and assistant dean for diversity, equity, and inclusion at the University of Kentucky (UK) College of Nursing and a nurse scientist for UK HealthCare’s Markey Cancer Center, both in Lexington.

. Investigators observed statistically significant decreases in the comprehensive score for financial toxicity (COST), defined as the psychological, material, and behavior aspects of financial hardship from cancer, using a paired t-test. The comparison of means for COST score for patients (n = 54) was 2.42 (

 = .021) for caregivers (n = 32). The total financial toxicity difference was 1.53 (

 = .13) for patients, and it was statistically significant for caregivers at 2.13 (

 = .041). Further, material conditions score was also statistically significant for caregivers with a t-score of 2.25 (

Participants in the study received an average financial benefit of $2500. The financial navigator secured a total of $124,600 for 48 participants with $24,000 toward travel, $16,000 toward urgent need, $9100 toward patient financial assistance, and $75,500 in copay assistance grants.

“As nurses we should understand that there are challenges and barriers to these costs and they are high,” Edward noted. “We need to be able to assess the social determinants of health. When you truly assess somebody’s social determinants of health, there are so many areas that come up that inform financial needs.”

, Edward highlighted implications of the study results and provided additional resources patients can use to help combat financial toxicity during cancer care.

“Nurses are big advocates for patients and when a patient shares, ‘I’m concerned about this; I’m not able to afford food for my family because I’m worried about paying for my chemotherapy or my treatment,’ then they need to be able to advocate for the patient so that they can bring up these concerns to the provider or the health care team.”

Edward explained that knowing what resources exist within the health system such as social workers, navigators, counselors, as well as financial assistance programs or patient grants are crucial. Cancer centers may have social workers who often aid with financial issues; however, they may be unable to assist with insurance or identifying barriers that exist with patient’s finances. Financial counselors may be an available resource at centers for those hurdles.

Of the 60 patients and 34 caregivers enrolled in the study, approximately one-third of patients (33.3%) and caregivers (31.3%) were living at or below the federal poverty level. The National Comprehensive Cancer Network’s Distress Thermometer and the Functional Assessment of Chronic Illness Therapy’s FACIT-COST measure were used to screen patients in the study, with a COST of less than 24 recorded for 90% of patients and 85.3% of caregivers. A distress thermometer score of more than 4 was recorded in 61.7% of patients and 54.5% of caregivers.

“I think we’re going to see a lot more individuals screening positive for financial toxicity in the future and that’s important,” Edward said. “We need to continue screening and understanding financial needs from a broader social determinants of health perspective…sometimes we would find that a patient would screen positive on the financial toxicity score, but on the distress thermometer they were fine, so they didn’t screen positive. That’s why it’s important that we use several tools, so we don’t lose anyone when we just go by a number.”

Of the 1179 patients screened in the study, 297 had a positive result for financial toxicity, with 219 meeting the study inclusion criteria. However, only 60 patients agreed to participate in CC Links and complete preintervention surveys, and 34 caregivers consented and completed the surveys. Although this indicates that only 27% of eligible patients enrolled in the study, 100% of eligible caregivers participated. Participants rated the intervention at 89% for acceptability and 88% for appropriateness.

The mean age for patients was 50.7 years and 46.6 years for caregivers. Most caregivers were a spouse or partner (50%). Other caregivers included adult child (25%), other relative (31.7%), or friend (11.7%). Most patients and caregivers were women (51.7% vs 52.9%) and White (91.7% vs 94.1%), and most had Medicare/Medicaid (64.4% vs 45.4%). Other insurance included TRICARE for 1 patient, and 5.1% of patients and 9.1% of caregivers had no insurance. Additionally, 30% of patients received a blood or bone marrow transplant (BMT) and 66.7% received chemotherapy. Furthermore, 36.7% of patients had lymphoma and 25% had leukemia.

One barrier for participation was contacting patients, and Edward noted that other compounding factors may have played a role, including general discomfort discussing finances. “To overcome that, we need to build trust with our patients and their caregivers before asking them these heavy financial questions and remind them we’re asking this information to help them,” Edward said. Additionally, some patients may wait until they receive bills or are struggling to pay them after being in treatment for a long period before calling a financial navigator with a worst-case scenario of experiencing bankruptcy or debt.

“We’ve noticed that when we talk about available resources, individuals will say, ‘I think somebody else could use that more than me,’ even if they’re struggling. That’s beautiful. It shows humanity, that [patients] do care and want someone else to benefit from this. We need to remind them that everyone’s eligible and anyone can join. We are assisting as many individuals as we can, so don’t feel bad about enrolling in this program,” Edward said.

Participants had an average of 3 in-person meetings (range, 0-21) and 5 telephone interactions (range, 1-23) with the financial navigator in the Division of Hematology and BMT at UK, a National Cancer Institute–designated cancer center where the study was conducted. Screening took place from April 2021 to January 2022 during inpatient and outpatient visits. The financial navigator aided patients and caregivers by screening participants, providing cost-of-care estimates, and coordinating financial assistance along with several other roles.

“Even though in this study we collected a lot of quantitative information and we’ve had positive outcomes, we also collected qualitative data and asked [patients and caregivers] what experiences they’ve had with the navigator,” Edward said. “Those words speak louder [and] show the tremendous impact that our financial navigation program had on these patients and their caregivers. Any data you can collect to show the impact that you’re having [are] going to speak volumes and help support work like this in the future.”

 for other populations. A financial and legal navigation intervention established in UK’s DanceBlue Pediatric Hematology & Oncology clinic in Lexington will be assisting patients affected by the impacts of childhood cancers.

“We recently received new funding from the Kentucky Pediatric Cancer Research Trust Fund [to] take 

 and adapt it to be on a virtual telehealth platform,” Edward explained. “We partnered with Triage Cancer, the nonprofit [organization]. They provide free education on legal and financial issues and practical issues for survivors and caregivers. We’re going to use them to see what happens if we partner with a thirdparty entity. Could the ROI [return on investment] be affected? Could we have an easier workflow of screening and referring patients to the assistance that they need?”

 study included a smaller sample size and the exclusion of nonEnglish-speaking participants. Additionally, the findings could not be generalized to other patients with cancer and caregivers, and the findings did not demonstrate feasibility.

Edward JS, McLouth LE, Rayens MK, Eisele LP, Davis TS, Hildebrandt G. Coverage and Cost-of-Care Links: addressing financial toxicity among patients with hematologic cancer and their caregivers. 

. Published online March 8, 2023. doi:10.1200/OP.22.00665

To evaluate the prevalence of financial toxicity and observe the effect of Coverage and Cost-of-Care Links, a program providing financial navigation, investigators initiated a nonrandomized study. 

Oncology Financial Navigator Interventions Provide Benefits to Patients With Hematologic Cancers

A new genetic test for patients with colorectal cancer (CRC) is under investigation at AdventHealth Cancer Institute in Orlando, Florida. From a simple blood draw, the test, called Signatera, can detect whether a patient has cancer and might allow them to avoid chemotherapy after tumor resection. The sequencing technology searches for circulating tumor DNA (ctDNA), which are very small amounts of tumor DNA in the bloodstream. 

“What we knew is that a lot of patients [with CRC] were cured with surgery alone. We just didn’t have a way to know which ones had microscopic cancer left in the blood, who needed chemotherapy and who did not,” Mohamedtaki Tejani, MD, FACS, a medical oncologist and director of the Gastrointestinal Oncology Program at the AdventHealth Cancer Institute said in an interview.

Before the test existed, any patient with stage II or III colon cancer was prescribed 6 months of chemotherapy. “I tell patients, it’s a game of chess and we want to know what the cancer’s next move is,” Tejani noted. “Rather than wait until we see it on the scan, we want to stem it right when it is starting, and this test allows for that.” 

There are multiple ctDNA testing approaches, and this one is called tumor-informed. It’s “what is used in a lot of ongoing trials, Tejani explained. “The tumor-informed approach is when providers take the patient’s tumor, sequence it, and know exactly what its genome is. Then they look for it in the blood. It’s a longer turnaround, but when providers get the results, they are confident that they are measuring the DNA…the patient’s tumor has.”

CRC is the fourth most common cancer in the United States and the second leading cause of cancer-related deaths.

 At AdventHealth, Tejani is leading a National Cancer Institute clinical trial and a large national study aimed at harnessing this technology to improve patient care. The trials are as follows. 

The BESPOKE study (NCT04264702) of ctDNA-guided therapy in CRC is being conducted under the leadership of principal investigator Ahmed Zakari, MD, chairman of AdventHealth Orlando’s Division of Hematology and director of Gastrointestinal Oncology. This is a multicenter, prospective, observational study of 2000 patients who have undergone surgery for stage I to IV colorectal cancer. Patients will receive tumor-informed ctDNA test results and may be recommended for postoperative systemic therapy or observation by their treating clinician. They will be followed for up to 2 years with serial ctDNA analysis performed during standard-of-care visits. The control arm includes matched stage I to IV CRC cases with a minimum of 2 years of clinical follow-up data. The primary end points include the effect of ctDNA testing on adjuvant treatment decisions and recurrence rates and the asymptomatic and without correlate imaging.

NCT04068103 is a phase 2/3 NCI collaborative trial investigating how well ctDNA testing works at predicting treatment for patients with stage IIA colon cancer after surgery. Tejani serves as principal investigator of this study, which aims to enroll over 1400 participants. After completion of study treatment, patients will be followed at 12 months and every 6 months thereafter for 2 years. Primary outcome measures include recurrence-free survival and clearance of ctDNA to undetectable levels in patients who had baseline ctDNA.

CIRCULATE-US (NCT05174169) is another NCI collaborative trial evaluating the use of adjuvant chemotherapy in patients with colon cancer based on evaluation of residual disease. The phase 2/3 trial will consider the type of chemotherapy to recommend to patients based on the presence or absence of ctDNA after surgery. Tejani will also serve as principal investigator of this study, and primary outcome measures will include time from randomization to both first ctDNA positive status and disease-free survival.

Another ongoing trial at AdventHealth is a phase 3 study evaluating chemotherapy with or without atezolizumab (Tecentriq) in patients with stage III mismatch repair–deficient colon cancer (NCT02912559).

This and the BESPOKE study are currently enrolling participants through a referral process with the AdventHealth Gastrointestinal Oncology Program.

CRC treatments are associated with many risks, including infertility, which may be mitigated by incorporating ctDNA testing into medical decisions, Tejani said, and he hopes that the test can also be used to prescreen for very early-stage colon cancer and to more effectively treat other cancers, like gynecologic and pancreatic tumors.

Estimated number of new cases for the four major cancers by sex and age group, 2022. American Cancer Society. Accessed March 30, 2023. bit.ly/3M1jseu

Estimated number of deaths for the four major cancers by sex and age group, 2022. American Cancer Society. Accessed March 30, 2023. bit.ly/3Uertip

BESPOKE study of ctDNA guided therapy in colorectal cancer. ClinicalTrials.gov. Updated March 21, 2023. Accessed March 31, 2023. https://clinicaltrials.gov/ ct2/show/NCT04264702 

Circulating tumor DNA testing in predicting treatment for patients with stage IIA colon cancer after surgery. ClinicalTrials.gov. Updated March 2, 2023. Accessed March 31, 2023. https://clinicaltrials.gov/ct2/show/NCT04068103

Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US). ClinicalTrials.gov. Updated March 24, 2023. Accessed March 31, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05174169

A021502 randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient DNA mismatch repair. AdventHealth Research Institute. Accessed March 31, 2023. bit.ly/42XH0qs

A new genetic test that may allow patients with colorectal cancer to avoid chemotherapy after tumor resection is under investigation at AdventHealth Cancer Institute in Orlando, Florida. 

Novel Detection Methods May End Chemotherapy for Patients With CRC

Immunotherapy has been unsuccessful in advanced solid tumors refractory to standard therapy, including PD-1 and CTLA-4, because of hostile tumor microenvironments. Thus, these types of patients with sarcomas and lung, ovarian, and gastrointestinal carcinomas represent a significant unmet need in this space.

The tide has begun to change, however, with the advent of a novel combination that can penetrate cold and immunotherapy-refractory tumors. Investigators of an ongoing phase 1a/1b multicohort trial (NCT03860272) are studying whether addition of adaptive immune activators increases the benefit derived from anti–PD-1 antibodies (Figure).

The backbone therapy for the trial is balstilimab, a PD-1 inhibitor previously submitted for FDA approval in the setting of recurrent metastatic cervical cancer that demonstrated single-agent efficacy with up to 20% response in a total of 140 patients with PD-L1–positive and PD-L1–negative disease.

 Balstilimab has also shown synergistic potential when combined with the CTLA-4 inhibitor zalifrelimab, resulting in an objective response rate (ORR) of 25.6% in 125 patients with recurrent or metastatic cervical cancer who relapsed after platinum-based therapy.

Botensilimab, a novel innate adaptive immune activator, is being investigated for its potential to improve the efficacy of immunotherapy in resistant tumors. “Botensilimab is a novel multifunctional CTLA-4 antibody designed to increase the benefits of immunotherapy…[in] patients with cold and resistant tumors,” Bruno B. Bockorny, MD, said in an interview with OncLive

“On the front end, botensilimab blocks CTLA-4 like other agents do, but on the back end, in the Fc portion, there are point mutations that increase the binding to the activating Fc gamma receptor on both antigen-presenting cells and natural killer [NK] cells. By doing that, we have a variety of unique benefits compared with the first-generation CTLA-4 [options]. We have a more substantial boost of the priming and memory formation of T cells and a more substantial depletion of the immunosuppressive T regulatory cells.” Bockorny is an assistant professor of medicine at Harvard Medical School and a medical oncologist and cellular biology researcher at Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

Over the past year, the combination has elicited promising results in patients with resistant/ refractory ovarian cancer and with microsatellite stable (MSS) colorectal cancer (CRC).

Bockorny noted that there are few options for patients with resistant/refractory ovarian cancer and that response rates are usually less than 10% with single-agent chemotherapies and investigational immunotherapy combinations. At the 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancers, however, data from the cohort of patients with resistant/refractory ovarian cancer showed durable responses.

Among 24 patients, the doublet elicited an overall response rate of 33% (95% CI, 15.6%-55.3%), which included 1 (4%) complete response (CR) and 7 (29%) partial responses (PR). Eight patients achieved stable disease, and 8 others experienced disease progression. At a median follow-up of 6.9 months (range, 1.7-29.2), the median duration of response (DOR) was not reached (NR; 95% CI, 4.2-NR). The disease control rate (DCR) was 67% (95% CI, 44.7%-84.4%).

“We were very encouraged because, aside from deep responses, the responses were also very durable,” Bockorny said. “We had multiple patients [experience] very prolonged clinical benefits, either disease stabilization or responses.” 

He added that with such a small patient population, investigators could not identify a biomarker that separated responders from nonresponders. “We are looking at, for instance, PD-1 as a potential marker; [however,] in this limited analysis of 24 patients, we are seeing that both patients with PD-1 [expression] are responding, but also [that those without] PD-1 expression are… responding.” Enrollment in the trial is ongoing. 

Patients with platinum-resistant or refractory, metastatic disease received 1 mg/kg (29%) or 2 mg/kg (71%) of botensilimab every 6 weeks plus 3 mg/kg of balstilimab every 2 weeks. Patients were allowed to have received prior immunotherapy, and crossover from prior botensilimab monotherapy was allowed.

Median patient age was 64 years (range, 37-75). Fourteen patients (58%) had an ECOG performance status of 0, and the remaining 10 (42%) had a status of 1. Bockorny noted that this was a very heavily pretreated cohort, with a median of 4 (range, 1-8) prior therapies. Nineteen patients (79%) had previously received bevacizumab (Avastin) and 5 (21%) had received immunotherapy. 

In terms of histology, 19 patients (79%) had high-grade serous disease, 1 (4%) had carcinosarcoma, and 2 (8%) each had mixed (clear cell/ endometrioid) or clear cell disease. Two of 13 patients (15%) were BRCA1/2 positive, and 7 of 16 (44%) were PD-L1 positive.

Bockorny said the combination displayed a manageable toxicity profile. The rate of grade 3/4 treatment-related adverse effects (TRAEs) was 41%, and most of these (21%) were attributable to grade 3 immune-mediated diarrhea/colitis.

Other TRAEs included nausea (all-grade, 33%; grade 3, 4%), vomiting (all-grade, 17%), fatigue (all-grade, 38%; grade 3, 4%), pyrexia (all-grade, 25%), rash (all-grade, 33%; grade 3, 4%), pruritus (all-grade, 33%), and arthralgia (all-grade, 21%).

“What’s particularly important for this safety profile is [that] we did not have any treatment-related deaths,” Bockorny said. “Importantly, we do not have any pneumonitis, hypophysitis, or myocarditis of any grade. It’s very consistent with the larger data sets of botensilimab and balstilimab, [in which] we see very little high-grade visceral toxicity outside of the [gastrointestinal] tract. That was an important safety point, and we were pleased to see that.”

Advances Lead to Phase 2 Development for MSS CRC

In the cohort of patients with MSS CRC (n = 70), median follow-up was 7 months (range, 2-31) and objective response rate, 23% (95% CI, 14%-34%). One CR was reported (1%), 15 patients had PR (21%), and most (53%) had stable disease. The disease control rate (DCR) was 76% (95% CI, 64%-85%). At the time of analysis, median overall survival (OS) had not been reached, and median progression-free survival was 4.1 months (95% CI, 2.8-5.5). The 12-month OS rate was 63% (95% CI, 45%-76%).

Among the 16 patients who responded, 11 continued to experience response at the time of data cutoff.5 Additional characteristics for these patients included refractory to prior immunotherapy (3 patients), tumor mutational burden data available (1 of 13), greater than 10/mut/Mb, and positive PD-L1 data of 1% or higher (1 of 8).

“In the past, conventional checkpoint inhibitors have been universally ineffective in MSS CRC,” Benjamin L. Schlechter, MD, said in an interview with OncLive. “The CTLA-4 antibody [of botensilimab], which is modified to decrease complement fixation and increase NK cell activation, hopefully can improve the safety profile and…the activity of the drug. We observed responses in patients with nonhepatic CRC [and] that’s a significant minority [of patients].” Schlechter is a senior physician at DanaFarber Cancer Institute and an instructor in medicine at Harvard Medical School, both in Boston, Massachusetts.

“The safety profile was manageable. There was a lot of colitis, but that’s something we [can handle]. This is the first—in a phase 1—significant response rate in colorectal cancer for MSS diseases using checkpoint inhibitor therapy, which is important.” 

Ninety-one percent of patients reported TRAEs of any grade, 40% reported grade 3 events, and 3%, grade 4 events. As Schlechter noted, the only grade 3/4 TRAEs to occur in more than 3 patients were diarrhea and colitis, with 20% of patients experiencing grade 3 events and 1%, grade 4 events. No grade 5 events were reported.

The combination had greater efficacy in patients without hepatic disease. Among those with-out active liver metastases, median OS was not reached and 12-month OS was 81% (95% CI, 66%-90%), whereas among those with active liver metastases, median OS was 9.4 months (95% CI, 6.1-NR), and 12-month OS, was 40% (95% CI, 17%-62%).

“[There was] significant disease control for patients with nonhepatic disease in refractory CRC, a population who would otherwise be receiving agents that have had very limited efficacy,” Schlechter said. “It was noted early on that patients with nonhepatic disease were deriving benefits and those with hepatic disease were not, and this is a known problem. We’ve known for a while that bulky hepatic metastasis, even in so-called hot tumors, have less of a response and that metastatic disease and liver [disease] have a worse response to checkpoint inhibitors, so it’s not shocking that this is happening.” 

As was the case with the ovarian cancer cohort, in this analysis patients received botensilimab at either 1 or 2 mg/kg every 6 weeks plus balstilimab at 3 mg/kg every 2 weeks. Patients were eligible to crossover from monotherapy to combination therapy or to fixed dosing of botensilimab 150 mg every 6 weeks plus balstilimab 450 mg every 3 weeks.

Schlechter added that the responses translated to a greater than 30% reduction in cancer burden. “There were patients with near-complete responses. So essentially all measurable disease, as far as we can tell, had been suppressed and the survival was prolonged…. Again, this is a population of patients with refractory CRC…[in whom] we measure responses usually in weeks, and survival…[in] weeks or a few months. To have a population of patients where the median survival is not met is impressive in a large phase 1 study.” 

A phase 2 and phase 3 study are planned for this cohort of patients, and the phase 2 portion is actively enrolling patients (NCT05608044).

 “There are going to be some dosing schedule assessments in phase 2, and there will be a standard-of-care control arm against [trifluridine/tipiracil (Lonsurf)] or regorafenib [Stivarga]. That’s an important step to lead to approval of the drug,” Schlechter said.

The trial will have 5 cohorts: Two will evaluate the combination of botensilimab and balstilimab with 2 different doses of botensilimab, 2 will evaluate botensilimab as monotherapy at 2 doses, and the fifth will be standard of care.

In terms of next research steps, Schlechter added, “We also need to figure out ways to manage patients with active metastatic liver disease. I think the race is on to figure out why patients with active metastatic disease in the liver don’t respond to checkpoint inhibitors generally, and this combination [in particular].… [We must] expand the population that’s eligible for this trial from 25% to 30% of all patients with refractory disease to 100%, or nearly 100%. Those are important areas of research, and we [will] see a lot about that over the next 2 years.”

Additional Efficacy Signals: Sarcoma, NSCLC

Durable responses were also seen in smaller subsets of patients treated with balstilimab plus botensilimab. 

At the 2022 Connective Tissue Oncology Society Annual Meeting, investigators presented results from the cohort of patients with refractory sarcoma (n = 13). The ORR was 46% (95% CI, 19%-75%), with 1 patient having a CR and 5 (38%), a PR. Stable disease was reported among 23% of patients, and the DCR was 69% (95% CI, 39%-91%). The median DOR and median OS were NR, and the 12-month OS rate was 77% (95% CI, 35%-94%).

Responses were ongoing in 4 of 6 patients at the time of data cutoff. Among those with angiosarcoma (n = 9), the ORR was 56%, with a DCR of 78%. The CR and 3 of the 4 ongoing responses were reported from this subgroup. Similar safety observations to the overall trial were reported, with no grade 4 or 5 events in this cohort.

Finally, data presented at the Society for Immunotherapy of Cancer 37th Annual Meeting & Preconference Programs showed that in patients with non–small cell lung cancer who received the combination (n = 4), the ORR was 50% (95% CI, 7%-93%), and both responses were PRs. The DCR was 75% (95% CI, 19%-99%), and the median DOR was NR. Both patients with an ORR had been previously treated with pembrolizumab (Keytruda), and response was ongoing in 1 patient.

Fc-engineered anti-CTLA-4 monoclonal antibody in advanced cancer. ClinicalTrials.gov. Updated September 22, 2022. Accessed March 29, 2023. 

https://clinicaltrials.gov/ct2/show/NCT03860272

Agenus provides update on balstilimab development. News release. Agenus. October 22, 2021. Accessed March 29, 2023. bit.ly/3M9anjA

O’Malley DM, Neffa M, Monk BJ, et al. Dual PD-1 and CTLA-4 checkpoint blockade using balstilimab and zalifrelimab combination as second-line treatment for advanced cervical cancer: an open-label phase II study. 

. 2022;40(7):762-771. doi:10.1200/JCO.21.02067

Bockorny B, Matulonis UA, O’Day SJ, et al. Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti–PD-1) in patients with recurrent platinum refractory/resistant ovarian cancer. Presented at: 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.

El-Khoueiry AB, Fakih M, Gordon MS, et al. Results from a phase 1a/1b study of botensilimab (BOT), a novel innate/adaptive immune activator, plus balstilimab (BAL; anti-PD-1 antibody) in metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC). 

. 2023;41(suppl 4):LBA8. doi:10.1200/JCO.2023.41.4_suppl.LBA8

A study of botensilimab and balstilimab for the treatment of colorectal cancer. ClinicalTrials.gov. Updated December 20, 2022. Accessed March 29, 2023. 

https://clinicaltrials.gov/ct2/show/NCT05608044

Wilky BA, Moser JC, Gordon MS, et al. A phase Ia/Ib study of botensilimab, a novel innate/adaptive immune activator, plus balstilimab for the treatment of patients with sarcoma. Presented at: 2022 Connective Tissue Oncology Society Annual Meeting; November 16-19, 2022; Vancouver, British Columbia, Canada.

Wilky B, El-Khoueiry A, Bullock A, et al. Botensilimab, a novel innate/adaptive immune activator, plus or minus balstilimab (anti-PD-1) in “cold” and I-O refractory metastatic solid tumors. 

. 2022;10(suppl 2). doi:10.1136/jitc-2022-SITC2022.0778

Investigators of an ongoing phase 1a/1b multicohort trial are studying whether addition of adaptive immune activators increases the benefit derived from anti–PD-1 antibodies in multiple tumor types.

PD-1/CTLA-4 Combination Drives Progress  Across Tumor Types

Despite a high-profile clinical disappointment, the TIGIT immune checkpoint remains an important target for anticancer therapy, with research programs testing novel agents moving forward in non–small cell lung cancer (NSCLC) and a range of other tumor types.

Investigators believe TIGIT plays a crucial role in inhibiting adaptive and innate immune responses against tumor cells, making it a promising anticancer target, particularly in combination with other immunotherapeutic strategies, such as immune checkpoint inhibitors (ICIs) directed at PD-1/PD-L1.

The exploration of TIGIT is part of the next steps in cancer immunotherapy aimed at overcoming therapeutic resistance that can take hold because of numerous factors that modulate the immune response, according to Jedd D. Wolchok, MD, PhD, FASCO.

Wolchok is a medical oncologist and consultant at Memorial Sloan Kettering Cancer Center and the director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, both in New York, New York, and the 2014 Giants of Cancer Care

 award winner for melanoma. He was among several leading immuno-oncologists who discussed the potential for targeting TIGIT during an American Society of Clinical Oncology (ASCO) Plenary Series session in December 2022.

During the past decade, findings from many clinical studies and analyses involving ICIs directed at PD-1/PD-L1 and CTLA-4 have led to the development of “a central dogma for cancer immunotherapy,” Wolchok said. This includes the realization that although some patients may achieve durable disease control with ICI therapy, numerous factors such as suppressive cells, a hostile microenvironment, and insufficient co-stimulation modulate responses.

As investigators focus on mechanisms that may help tumor cells evade an immune response, TIGIT has emerged as a target of interest. More than 30 monoclonal antibodies (mAbs) directed at TIGIT are in development. Although most of these novel therapies are in preclinical or phase 1 stages, the pipeline includes several agents that have advanced to phase 3 testing (

TIGIT, which stands for T-cell immunoglobulin and ITIM domain, is among the coinhibitory receptors that help regulate T-cell responses, a family that includes PD-1, CTLA-4, and LAG-3. Investigators discovered TIGIT through bioinformatic analyses about 15 years ago, with different research groups variously identifying it as WUCAM, Vstm3, and Vsig9.

As a surface protein, TIGIT is expressed on multiple immune cells, including memory T cells and natural killer (NK) cells.

 Findings from several studies have detected TIGIT overexpression in the microenvironment of numerous tumor types, including lung, kidney, liver, glioma, melanoma, colorectal, gastric, and neuroblastomas.

In one pan-cancer analysis, investigators found that TIGIT expression was upregulated in most of 33 cancer types in a comparison of normal and tumor samples from 2 databases.

Moreover, high TIGIT expression was associated with a poor prognosis for overall survival (OS) in tumor samples from patients with renal cell and papillary cell carcinomas of the kidney, lower-grade gliomas of the brain, and uveal melanoma.

Over the years, investigators’ views on TIGIT’s role in the immune system have evolved into an understanding that it is more complex than initially envisioned, according to Solange Peters, MD, PhD, the 2020-2022 president of the European Society for Medical Oncology (ESMO) and chair of medical oncology at Lausanne University in Switzerland.

TIGIT is among 4 regulatory receptors expressed on T cells or NK cells that are part of the CD226 pathway, Peters said during the ASCO Plenary Series session. CD226 is a co-stimulatory receptor that interacts primarily with CD155 but also with CD112 on the tumor cells to activate T cells and NK cells, thus generating an immune response that promotes cancer cell killing, Peters said. The receptors in the CD226 axis, as the pathway is known, that inhibit cancer cell killing are TIGIT, CD96, and PVRIG (

“It’s quite important to imagine that anti-TIGIT [therapy] is one of the ways to reactivate the interaction of CD226 with CD155,” Peters said. “The other important point to keep in mind [is that] it’s probable that TIGIT is also expressed on Tregs [regulatory T cells]. So, you have here a mechanism of ADCC—antibody-directed cell cycle cytotoxicity—which would potentially be related to an anti-TIGIT monoclonal antibody, resulting in a depletion of Treg cells.”

Of the inhibitory receptors in the CD226 axis, TIGIT is the most extensively studied, according to David Planchard, MD, PhD, who discussed the landscape during a symposium at the ESMO Immuno-Oncology Congress in December 2022. GSK, which is among the pharmaceutical companies developing TIGIT-targeting therapies, sponsored the program.

 Planchard is head of the thoracic pathology committee at the Institut Gustave Roussy in Villejuif, France.

TIGIT-targeting antibodies are being tested in nearly 20 tumor types. Studies involving patients with NSCLC represent the largest slice of the development pie. Testing also is under way in digestive tract, gynecologic, and genitourinary cancers as well as in B-cell hematologic malignancies and multiple myeloma.

In NSCLC, there is a need for new strategies to improve responses to immunotherapy, Peters said. ICI therapy is established for the frontline treatment of most patients with advanced disease without 

 alterations as monotherapy or in combination with chemotherapy, she noted. Patients with PD-L1 expression of 50% or greater are candidates for frontline PD-1/PD-L1–targeting monotherapy.

However, at least 1 in 5 patients with high PD-L1 expression will have progressive disease as the best response to ICI monotherapy, and many patients whose disease stabilizes with ICI therapy will eventually experience progression, Peters said. “We have to face this unmet need of addressing immune checkpoint resistance, this acquired resistance, where initially you have a response and later, down the road, progression of the disease,” she said. “All of this represents potential opportunities for improvement of our treatment strategies.”

Although TIGIT continues to attract interest in the drug development field, clinical findings for novel antibodies targeting the checkpoint have been mixed. AntiTIGIT monotherapy resulted in objective response rates (ORRs) ranging from 0% to 5% across several trials in advanced solid tumors, Planchard said. Treatmentrelated adverse events of any grade included rash, pruritus, infusion site reactions, and anemia.

As combination therapy, tiragolumab (RG6058), the most advanced anti-TIGIT mAb in terms of development, initially demonstrated clinical benefit in the phase 2 CITYSCAPE trial (NCT03563716) but then faltered in phase 3 studies.

In CITYSCAPE, patients with chemotherapy- naïve recurrent or metastatic PD-L1–positive NSCLC were randomly assigned to receive atezolizumab (Tecentriq), a PD-L1–directed ICI, with tiragolumab or placebo. PD-L1 positivity was defined as a tumor proportion score of 1% or greater.

In the primary analysis, the novel combination resulted in an ORR of 31.3% (95% CI, 19.5%-43.2%) in 21 of 67 patients compared with 16.2% (95% CI, 6.7%-25.7%) in 11 of 68 patients who received atezolizumab plus placebo. Median progression- free survival (PFS) was 5.4 months (95% CI, 4.2-not estimable) with tiragolumab plus atezolizumab compared with 3.6 months (95% CI, 2.7-4.4) with atezolizumab alone (HR, 0.57; 95% CI, 0.37-0.90; 

However, prospects for tiragolumab dimmed after findings from 2 phase 3 trials failed to establish a benefit with the addition of the agent to standard therapies.

In March 2022, Genentech, a member of the Roche Group, announced that the combination of tiragolumab plus atezolizumab and chemotherapy did not reach its coprimary end points of PFS and OS in the phase 3 SKYSCRAPER-02 study (NCT04256421) as first-line therapy in patients with extensive-stage SCLC. Patients who had not received prior systemic treatment for extensive-stage disease were randomly assigned to receive tiragolumab or placebo in combination with atezolizumab, carboplatin, and etoposide.

After a median follow-up of 14.3 months, median PFS in the primary analysis set was 5.4 months (95% CI, 4.7-5.5) in the tiragolumab cohort (n = 196) and 5.6 months (95% CI, 5.4-5.9) in the standard therapy group (n = 201). Interim median OS was 13.6 months with both regimens.

In May 2022, Genentech disclosed that the addition of tiragolumab to atezolizumab failed to show an improvement in PFS over atezolizumab alone as first-line therapy for patients with PD-L1high locally advanced or metastatic NSCLC in the phase 3 SKYSCRAPER-01 study (NCT04294810). Data from the first analysis for the coprimary end point of OS were immature, the company said. Details of the findings were not disclosed.

News of the SKYSCRAPER-01 results rattled confidence in the potential for developing therapies aimed at the TIGIT checkpoint, according to market analysts.

 Nevertheless, evaluation of tiragolumab is ongoing in SKYSCRAPER-01 and several other NSCLC settings as well as in studies involving patients with recurrent/metastatic PD-L1–positive squamous cell head and neck carcinoma, esophageal carcinoma, and cervical cancer.

The outlook for TIGIT-targeting therapies brightened in December 2022 with the release of findings from the phase 2 ARC-7 trial (NCT04262856), in which the anti-TIGIT mAb domvanalimab was evaluated as part of doublet and triplet therapy compared with a PD-1directed ICI in NSCLC.

Patients with stage IV NSCLC who had not been treated for metastatic disease and had PD-L1 expression of 50% or greater were randomly assigned to 1 of 3 study arms: zimberelimab (Z), a PD-1 inhibitor approved in China for classical Hodgkin lymphoma; domvanalimab plus zimberelimab (DZ); or etrumadenant, a novel adenosine 2 receptor antagonist, plus domvanalimab and zimberelimab (EDZ). Crossover from arm Z to the EDZ regimen was permitted (

The rationale for adding etrumadenant to the mix stems from the immuno-suppressant role that adenosine plays. The molecule affects Tregs as well as T effector cells and dendritic cells and is a source of interest to investigators seeking additional mechanisms to overcome immune resistance in cancer therapy, Wolchok said.

During the ASCO Plenary Series program, Melissa L. Johnson, MD, presented interim efficacy findings from ARC-7. Johnson is director of lung cancer research at Sarah Cannon Research Institute and is chair of the oncology department and a member of the medical executive committee at TriStar Centennial Medical Center, both in Nashville, Tennessee.

The findings involved 133 patients randomly assigned to an ARC-7 treatment arm at least 13 weeks prior to data cutoff in August 2022, enabling investigators to review at least 2 scans from baseline to assess responses.

The use of domvanalimab improved ORRs and PFS compared with zimberelimab alone. The ORRs were 27% in the Z arm, 41% in the DZ group, and 40% in the EDZ cohort; all responses were partial. The 6-month PFS rates were 43%, 65%, and 63%, respectively, in the Z, DZ, and EDZ arms. The median PFS rate was 5.4 months in the Z arm, 12.0 months in the DZ group, and 10.9 months with EDZ therapy. Those values translated into HRs of 0.55 and 0.65 for doublet and triplet therapy compared with antiPD-1 monotherapy.

In terms of safety, the most common treatment-emergent adverse events were fatigue, nausea, constipation, dyspnea, decreased appetite, and pneumonia. Events of grade 3 or greater severity were observed in 58% of participants in the Z arm, 47% in the DZ group, and 52% in the EDZ arm. This included grade 5 events related to study treatment involving 1 patient with interstitial lung disease in the Z arm, 1 participant with myocarditis in the DZ group, and 2 with congestive heart failure in the EDZ arm.

The results support continued development of domvanalimab in NSCLC, which is ongoing in 3 phase 3 studies: ARC-10 (NCT04736173), STAR-121 (NCT05502237), and PACIFIC-8 (NCT05211895), according to Johnson.

The findings also may help bolster confidence in targeting TIGIT as a therapeutic strategy. “There have been mixed signals from prior studies looking at TIGIT targeting. The promising results of the combination immunotherapy treatment in this study support further investigation, and if confirmed, could lead to a new standard of care for patients with advanced lung cancer,” Lauren A. Byers, MD, said in speaking as an ASCO expert in advance of the Plenary Series program.

 Byers is an assistant professor at The University of Texas MD Anderson Cancer Center in Houston.

Of note, domvanalimab is designed differently from other TIGIT-targeting mAbs, including tiragolumab, in that the Fc region of the antibody is silent, thus avoiding the depletion of TIGITbearing immune cells that may augment the immune response.

Findings for several other TIGIT-targeting therapies tested in combination regimens have been a patchwork of positive and negative data.

Ociperlimab, an anti-TIGIT antibody with an active Fc domain, is paired with tislelizumab, an anti–PD-1 mAb approved in China in combination with chemotherapy for patients with NSCLC, in the ongoing phase 1b AdvanTIG-105 study (NCT04047862). The study has 10 cohorts, including separate groups for patients with previously untreated metastatic for squamous NSCLC (cohort 1) and nonsquamous NSCLC (cohort 2).

The ORR was 57.5% (95% CI, 40.9%-73.0%) among 40 patients with squamous NSCLC in cohort 1 and 54.8% (95% CI, 38.7%-70.2%) among 42 participants with nonsquamous disease in cohort 2, according to results reported during the ESMO Congress in September 2022. The median duration of response was not evaluable in both cohorts.

The most common treatment-related adverse events of any grade were anemia, decreased neutrophil counts, and decreased white blood cell counts. Events of grade 3 or greater severity were observed in 48.8% of patients, including serious events in 16.7%.

However, the combination of ociperlimab plus tislelizumab was not as effective in patients with locally advanced or metastatic NSCLC who had received prior treatment with an ICI. In cohort 5 of AdvanTIG-105, the ORR was 8.0% (95% CI, 1.0%26.0%), with only 2 partial responses recorded among 25 patients.

Meanwhile, the ORR reached 65.0% (95% CI, 48.3%-79.4%) among 40 patients with extensive-stage SCLC not previously treated for metastatic disease who received ociperlimab plus tislelizumab and a chemotherapy doublet in cohort 4 of AdvanTIG-105. The median duration of response was 4.3 months (95% CI, 3.2-5.6).

Several studies testing ociperlimab-containing regimens are continuing, including the phase 3 AdvanTIG-302 trial (NCT04746924) in patients with locally advanced, unresectable, or metastatic NSCLC with PD-L1 expression of 50% or greater, previously untreated in the metastatic setting.

Investigators also have taken the approach of combining vibostolimab, an anti-TIGIT mAb, with pembrolizumab (Keytruda), a PD-1–directed ICI, in the same therapy, in a coformulation designated MK-7684A.

When the 2 drugs were tested as separate agents, the combination of vibostolimab plus pembrolizumab demonstrated an ORR of 26%, including 1 complete response, among 39 patients with PD-1/PD-L-1–naïve NSCLC treated during a first-in-human phase 1 study (NCT02964013).

However, the coformulation failed to improve PFS compared with docetaxel, a standard of care, in patients with previously treated metastatic NSCLC in an arm of the phase 2 KeyVibe-002 trial (NCT04725188), according to Merck, the company developing the therapy.

The study, which is active but no longer recruiting participants, consists of an open-label arm in which MK-7684A was administered alone and 2 blinded arms in which participants received MK-7684A plus docetaxel or placebo plus docetaxel.

Findings from the open-label arm showed that MK-7684A alone “did not reach statistical significance for the primary end point of PFS and was numerically less effective compared with docetaxel,” Merck said in a news release on March 16, 2023. Study investigators were advised to switch patients to standard care unless they are benefiting from therapy with MK-7684A alone.

At the same time, Merck is continuing to test the efficacy of MK-7684A when added to docetaxel compared with docetaxel alone in KeyVibe-002. The company also is pursuing studies of the coformulation in clinical trials recruiting more than 4000 patients, including in several large phase 3 trials in NSCLC and melanoma.

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Despite a high-profile clinical disappointment, the TIGIT immune checkpoint remains an important target for anticancer therapy, with research programs testing novel agents moving forward in non–small cell lung cancer and a range of other tumor types.

Vol. 24/No. 8 | Oncology Live®

O’Shaughnessy Showcases Highlights in Breast Cancer Guiding 2023 IBC Congresses

Oncology Financial Navigator Interventions Provide Benefits to Patients With Hematologic Cancers

Novel Detection Methods May End Chemotherapy for Patients With CRC

PD-1/CTLA-4 Combination Drives Progress Across Tumor Types

TIGIT Remains a Tempting Target for Immunotherapy Combinations, Despite Setbacks

Nonclinical Societal Issues Create Problematic Intersection With Cancer Prevention