(UroToday.com) Renal cell carcinoma is the most common kidney cancer and constitutes approximately 3% of all malignant tumors in adults. Renal cell carcinoma is often first detected at an advanced stage, with 25% to 30% of patients with metastatic disease at diagnosis. Avelumab is a human immunoglobulin G1 (IgG1) monoclonal antibody targeting PD-L1 that was approved in combination with axitinib, a VEGFR TKI, for first-line treatment of advanced RCC. In the phase 3 JAVELIN Renal 101 trial, avelumab + axitinib demonstrated significantly longer progression-free survival compared with sunitinib in patients who received these as first-line treatment for advanced RCC.1 There are limited data on the outcomes of patients receiving second-line therapy following immunotherapies plus tyrosine-kinase inhibitors in the first-line setting. At the 2021 ASCO virtual meeting, Dr. Laurence Albiges and colleagues presented results of patients with advanced RCC who had received first-line avelumab + axitinib in the phase 3 JAVELIN Renal 101 trial and went on to receive subsequent treatment.
In the JAVELIN Renal 101 trial, treatment-naïve patients with advanced RCC were randomized 1:1 to receive avelumab (10 mg/kg intravenously every 2 weeks) + axitinib (5 mg orally twice daily) or sunitinib (50 mg orally once daily for 4 weeks of a 6-week cycle). At the cutoff date for the third interim analysis (April 28, 2020), patients who received first-line avelumab + axitinib (n = 442) and received any subsequent lines of treatment were assessed. This analysis reported the overall survival (OS), progression-free survival on next-line systemic therapy (PFS2) per type of treatment, and duration of second-line treatment.
At the cutoff date for the third interim analysis, 346 of 442 patients (78.3%) in the avelumab + axitinib arm discontinued treatment with avelumab, and 338 of 442 (76.5%) discontinued axitinib. At least one second-line anticancer drug therapy was received by 204/442 patients following first-line avelumab + axitinib treatment:
The summary of second-line anticancer drug therapy is as follows:
The most common second-line treatment was VEGF(R) received by 132 of 204 patients, and cabozantinib was the most frequently used VEGF(R) TKI treatment. Second-line PD-(L)1 treatment was given in 19 of 024 patients, with nivolumab being the most frequently used agent. The median OS in patients receiving second-line VEGF(R) or PD-(L)1 inhibitors was 29.8 months (95% CI 24.1-42.2) and not evaluable, respectively:
There were 20 of 204 patients that received second-line combination therapy with VEGF(R) + other, with the combination of lenvatinib + everolimus being more frequently used, while 21 of 204 patients received any other combination therapy. The median OS in patients receiving second-line combination VEGF(R) + other or any other combination therapy was not reached in either arm. As follows is the summary of OS:
Dr. Laurence Albiges concluded her presentation of the JAVELIN Renal 101study with the following take-home messages:
- In patients with advanced RCC who received second-line therapies following first-line treatment with avelumab + axitinib, single-agent VEGF(R) inhibitor was the most frequent therapy
- The overall survival in patients receiving second-line treatment was longer compared with patients who discontinued avelumab + axitinib and did not receive any subsequent treatment
- These findings suggest that the use of second-line treatment upon discontinuation of the combination of a checkpoint inhibitor and a VEGFR TKI is likely to provide a benefit, although further studies are warranted to establish the optimal sequence of treatment
Clinical trial information: NCT02684006
Presented by: Laurence Albiges, MD, PhD, Medical Oncologist, Department of Cancer Medicine, Gustave Roussy Cancer Campus, University of Paris Sud
Co-Authors: Martin H Voss, Brian I. Rini, Gwenaelle Gravis, Marc-Oliver Grimm, Paul D. Nathan, Georg A. Bjarnason, Yoshihiko Tomita, Konstantin Penkov, Bradley McGregor, Bo Huang, Despina Thomaidou, Mariangela Mariani, Alessandra Di Pietro, Toni K. Choueiri; Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Vanderbilt-Ingram Cancer Center, Nashville, TN; Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France; Department of Urology, Universitaetsklinikum Jena, Jena, Germany; Mount Vernon Cancer Centre, Northwood, United Kingdom; Sunnybrook Research Institute, Toronto, ON, Canada; Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Private Medical Institution “Euromedservice”, Saint-Petersburg, Russian Federation; Dana-Farber Cancer Institute, Boston, MA; Pfizer, Groton, CT; Pfizer Hellas, Athens, Greece; Pfizer srl, Milan, Italy; Dana-Farber Cancer Institute, The Lank Center for Genitourinary Oncology, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
References:
1. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 2019;380(12):1103-1115.