Meredith Regan, ScD.

Patients with advanced renal cell carcinoma (RCC) who receive combination PD-1/CTLA-4 blockade can experience periods of durable benefit and toxicity after treatment discontinuation. According to results of the phase 3 CheckMate 214 trial presented by Meredith Regan, ScD, at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, nivolumab/ipilimumab prolongs treatment-free survival, both with and without toxicity, in patients with previously untreated advanced clear cell RCC. In this interview with i3 Health, Dr. Regan explains the significance of these results and discusses the future of research and treatment for advanced RCC.

Can you comment on the significance of your findings regarding nivolumab/ipilimumab for patients with previously untreated advanced clear cell RCC?

Meredith Regan, ScD: In CheckMate 214, we have quantified treatment-free survival with nivolumab/ipilimumab, an immune checkpoint inhibitor combination, compared with sunitinib, a vascular endothelial growth factor (VEGF) targeted therapy. Treatment-free survival was twice as long with nivolumab/ipilimumab than sunitinib in patients with poor or intermediate prognostic risk, and three times as long in patients with favorable risk. Whether treatment-free survival was observed with PD-1/VEGF combination therapy, including pembrolizumab/axitinib and avelumab/axitinib, or with nivolumab/cabozantinib, has not been reported.

What are the next steps for this research?

Dr. Regan: In the shorter run, we've aimed to develop an approach for analyzing the clinical trial data that integrated the efficacy and side effects of immuno-oncology therapies to aid clinicians and patients in their discussions about treatment goals and treatment decision making. We hope that other RCC trials will also use our approach, as this would contribute more to the discussion about what patients can expect when receiving PD-1–based combination therapy. Additionally, as we work to develop regimens that will improve overall survival and periods of disease remission, we need an end point and analysis to assess that goal. We aim to fill this void.

How do you foresee the treatment of advanced RCC evolving in the future?

Dr. Regan: In addition to the results and conclusions included in our presentation, we're trying to encourage discussion about the possibility of developing regimens for RCC that don't require patients to be on continuous treatment.

About Dr. Regan

Meredith Regan, ScD, is an Associate Professor of Medicine at Harvard Medical School and an Associate Professor in the Department of Data Science at Dana-Farber Cancer Institute. She is also Director of the Biostatistics and Computational Biology Core of the Dana-Farber/Harvard Cancer Center Prostate Cancer Specialized Program of Research Excellence (SPORE), Core Co-Director of the Breast Cancer SPORE, and Director of the Statistical and Data Management Center of the International Breast Cancer Study Group (IBCSG). Dr. Regan's research focuses on statistical methods in cancer research, with particular interest in breast and genitourinary cancers. She has published numerous publications in peer-reviewed journals.

For More Information

Regan M, Jegede OA, Mantia C, et al (2020). Treatment-free survival, with and without toxicity, after immuno-oncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214. Ann Oncol (ESMO Virtual Congress Abstracts), 31(suppl_4): S550. Abstract 713P. DOI:10.1016/annonc/annonc274

Motzer RJ, Escudier B, McDermott DF, et al (2020). Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial. J Immunother Cancer, 8(2). DOI:10.1136/jitc-2020-000891

Rini BI, Plimack ER, Stus V, et al (2019). Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med, 380(1116-1127). DOI:10.1056/NEJMoa1816714

Motzer RJ, Penkov K, Haanen J, et al (2019). Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med, 380:1103-1115. DOI:10.1056/NEJMoa1816047

Choueiri TK, Powles T, Burotto M, et al (2020). Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Ann Oncol, 31(suppl_4):S1159 Abstract 6960_PR. DOI:10.1016/j.annonc.2020.08.2257

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.