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E-Newsletter - November 2025
2024-2025 Most Significant Alliance Publications

Alliance names publications on bladder, Pancreatic, colorectal and skin cancer as most significant in 2024-2025

The Alliance of Clinical Trials in Oncology has selected four manuscripts of out 51 published in 2024-2025 as the most significant of the year. Four papers on the topics of bladder, pancreatic, colorectal and skin cancer were chosen by the Alliance Publications Committee, led by Co-Chairs Apar Ganti, MD, of the University of Nebraska Medical Center and John Grecula, MD, of The Ohio State University Comprehensive Cancer Center.

Selection of the most significant manuscripts was based on review by scientific leadership as well as by a separate review panel. Disease and modality committee chairs and the principal investigators of the Cancer Control Program, Statistics and Data Management Program, and Translational Research Program are asked to nominate up to three manuscripts from their committee or program. Each nominated manuscript must satisfy at least one of the following criteria:

Potential to change the standard of care.
Potential to change the way clinical trials are designed and/or executed.
Potential to change our understanding of cancer biology.

At least one nomination from each committee and program needed to have a junior investigator (one who has completed training within the previous 10 years) as first author, if such a manuscript has been published and meets the qualifications. In nominating a publication, committee chairs and program principal investigators are asked to explain why the published manuscript merited consideration.

The members of the review panel, who were nominated by the disease and modality committee chairs and by the CCP, SDMC, and TRP principal investigators, evaluated the nominated manuscripts according to the criteria above and provided each manuscript with an individual merit score. Members of the Alliance Publications Committee then discussed the merit scores and the comments made by the reviewers to make their final determination of the most significant manuscripts of the year. The four manuscripts are:

Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma
N Engl J Med. 2025 Jan 2;392(1):45-55
Andrea B. Apolo, Karla V. Ballman, Guru Sonpavde, Stephanie Berg, William Y. Kim, Rahul Parikh, Min Yuen Teo, Randy F. Sweis, Daniel M. Geynisman, Petros Grivas, Gurkamal Chatta, Zachery Roger Reichert, Joseph W. Kim, Mehmet Asim Bilen, Bradley McGregor, Parminder Singh, Abhishek Tripathi, Suzanne Cole, Nicholas Simon, Scot Niglio, Lisa Ley, Lisa Cordes, Sandy Srinivas, Jiaoti Huang, Meagan Odegaard, Colleen Watt, Daniel Petrylak, Jeannie Hoffman-Censits, Yujia Wen, Olwen Hahn, Cecilia Mitchell, Alan Tan, Howard Streicher, Elad Sharon, Helen Moon, Michael Woods, Susan Halabi, Gabriela Perez Burbano, Michael J Morris, Jonathan E Rosenberg

Study: A031501 AMBASSADOR | Alliance Funding: U10CA180821, U10CA180882

Synopsis: Researchers wanted to see if giving patients an immunotherapy drug called pembrolizumab after bladder cancer surgery could help prevent the cancer from coming back. This was compared to observation. About 700 people with high-risk bladder cancer and had their bladder removed were enrolled in the trial. One group got pembrolizumab (an immune therapy) every three weeks for one year. The other group was just observed without extra treatment.

As a result of the trial, people who got pembrolizumab stayed cancer-free for longer: about 30 months compared to 14 months in the observation group. Overall survival was about the same for now, but more follow-up is needed. Patient reported side effects were mostly mild, such as tiredness and skin irritation.

The results of this study are important pembrolizumab after surgery can help keep bladder cancer from coming back, even for people who can’t get chemotherapy. It’s a new option for high-risk patients.

Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors
N Engl J Med. 2025 Feb 13;392(7):653-665
Jennifer A. Chan, Susan Geyer, Tyler Zemla, Michael V. Knopp, Spencer Behr, Sydney Pulsipher, Fang-Shu Ou, Amylou C. Dueck, Jared Acoba, Ardaman Shergill, Edward M. Wolin, Thorvardur R. Halfdanarson, Bhavana Konda, Nikolaos A. Trikalinos, Bernard Tawfik, Nitya Raj, Shagufta Shaheen, Namrata Vijayvergia, Arvind Dasari, Jonathan R. Strosberg, Elise C. Kohn, Matthew H. Kulke, Eileen M. O’Reilly, Jeffrey A. Meyerhardt

Study: A021602 | Alliance Funding: U10CA180821, U10CA180882

Synposis: Researchers tested whether cabozantinib, a targeted cancer therapy drug called a tyrosine kinase inhibitor, could help people with advanced neuroendocrine tumors (NETs) that had gotten worse after other treatments. These tumors can grow in the pancreas or other parts of the digestive system.

About 200 adults with progressive neuroendocrine tumors that could not be removed by surgery and had already been treated with other medicines were enrolled in the trial. Participants were randomly assigned to get cabozantinib or a placebo (a pill with no active drug). The main goal was to see how long patients lived without their cancer getting worse (progression-free survival).

The trial found that people taking cabozantinib stayed stable for longer than those on placebo. People with pancreatic NETs were stable for about 14 months vs. 4.5 months. Patients with other NETs were stable for about 8.5 months vs. 4 months. Side effects were common but mostly manageable. The most frequent were high blood pressure, diarrhea, tiredness, and hand-foot skin reactions.

The study shows that cabozantinib offers a new treatment option for patients with advanced NETs who have few choices left. It can slow down cancer growth and help people live longer without disease progression.

Read the news release on the trial.

Plant-based Diet and Survival Among Patients with Metastatic Colorectal Cancer
J Natl Cancer Inst. 2025 Jan 1;117(1):169-179
En Cheng, Fang-Shu Ou, Clare Gatten, Chao Ma, Alan P. Venook, Heinz-Josef Len, Eileen M. O’Reill, Peter T. Campbell, Chaoyuan Kuang, Bette J Caan, Charles D. Blanke, Kimmie Ng, Jeffrey A. Meyerhardt
*Dr. Cheng is a junior investigator

Study: CALGB-80405 | Alliance Funding: U10CA180821, U10CA180882

Synposis: This study examined whether eating more healthy plant-based foods could help people with metastatic colorectal cancer live longer. The team derived a cohort of 1,284 patients with metastatic colorectal cancer that had previously enrolled in CALGB/SWOG 80405 study and reviewed food frequency questionnaires completed after diagnosis.

The study found that patients who scored highest on a healthy plant-based diet index had a 24% lower risk of death compared to those with the lowest scores. Median overall survival was highest, 36 months, in the highest plant-based diet group compared to 30 months for the lowest plant-based diet group: about 30 months. Results were consistent across age, sex, and treatment types.

This study is significant as people with advanced colorectal cancer may find that focusing on a healthy plant-based diet may help improve survival and overall health alongside medical treatment. The researchers suggest that future trials may consider adding plant-based dietary interventions in addition to standard treatments for people with metastatic colorectal cancer.

Phase II (Alliance A091802) Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma
J Clin Oncol. 2025 Jul 20;43(21):2398-2408
Dan P. Zandberg, Jacob B. Allred, Ari J. Rosenberg, John M. Kaczmar, Paul Swiecicki, Ricklie A. Julian, Andrew S. Poklepovic, Jessica R. Bauman, Minh D. Phan, Nabil F. Saba, Edgardo Rivera, Kendrith Rowlan, Diwakar Davar, Julia Cordes, Alan L. Ho, Miao Zhang, Stephanie A. Berg, Pamela N. Munster, Gary K. Schwartz

Study: A091802 | Alliance Funding: U10CA180821, U10CA180882

Synposis: Researchers tested whether adding the monoclonal antibody cetuximab to the immunotherapy drug avelumab could improve outcomes for people with advanced cutaneous squamous cell carcinoma (cSCC)—a type of skin cancer that has spread or cannot be removed by surgery. A total of 60 patients with advanced cSCC who had not previously received immunotherapy or cetuximab for advanced disease were ultimately enrolled.

One group in the study received avelumab alone every 2 weeks. The other group received avelumab plus cetuximab every 2 weeks. Treatment continued for up to 2 years. Patients on avelumab alone could switch to the combination if their cancer worsened.

The study found that the combination of avelumab and cetuximab helped patients stay cancer-free longer. The median time before cancer worsened was 11.1 months with the combination vs. 3.0 months with avelumab alone. Response rates were also slightly higher with the combination treatment (about 28% vs. 21%). Side effects were more common with the combination cohort, especially rash and infusion reactions.

The results are significant as adding cetuximab to avelumab may help control advanced skin cancer for longer than avelumab alone, offering a new treatment option.

Read the news release.

HONORABLE MENTION PUBLICATIONS

Recurrence of Non–Small Cell Lung Cancer With Visceral Pleural Invasion
JAMA Oncol. 2024;10(9):1179–1186
Study: CALGB-140503 | Alliance Funding: U10CA180821, U10CA180882

Identification of Meaningful Individual-level Change Thresholds for Worsening on the Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Qual Life Res. 2025 Feb;34(2):495-507
Study: AFT-39 | Alliance Funding: PCORI IHS-1511-33392

Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer
J Clin Oncol. 2025 Apr;43(10):1229-1239
Study: CALGB-9741 | Alliance Funding: U10CA180821, U10CA180882, U24CA196171