The addition of the monoclonal antibody atezolizumab to the tyrosine kinase inhibitor cabozantinib failed to improve progression-free survival and overall survival vs cabozantinib alone in patients with advanced renal cell carcinoma (previously treated with an immune checkpoint inhibitor) in the phase III CONTACT-03 trial.1 The results of this study were published in The Lancet to coincide with the presentation at the 2023 ASCO Annual Meeting.2
According to central review, median progression-free survival was 10.6 months with the addition of atezolizumab compared with 10.8 months with cabozantinib alone. The 12-month progression-free survival rates were 44% and 48%, respectively. There was no appreciable difference in progression-free survival between the two arms across most prespecified subgroups. An interim analysis of overall survival revealed a similar trend; the median overall survival was 25.7 months for the experimental arm vs not evaluable for cabozantinib alone.
“The addition of atezolizumab to cabozantinib did not result in improved clinical outcomes in patients with metastatic renal cell carcinoma who experienced disease progression on or after prior immune checkpoint inhibitor treatment,” said Toni K. Choueiri, MD, Director of the Lank Center for Genitourinary Oncology, and Medical Director of International Strategic Initiatives, Dana-Farber Cancer Institute, and Professor, Harvard Medical School, Boston. “In my opinion and the opinion of the investigators, these data highlight the importance of randomized, prospective assessment of rechallenge with checkpoint inhibitors in renal cell carcinoma and potentially in other tumor types.”
“These data highlight the importance of randomized, prospective assessment of rechallenge with checkpoint inhibitors in renal cell carcinoma and potentially in other tumor types.”— Toni K. Choueiri, MD
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The phase III CONTACT-03 trial was designed to evaluate the benefit of rechallenge with an immune checkpoint inhibitor after radiographic disease progression on or after treatment with an immune checkpoint inhibitor. The study enrolled patients with metastatic or advanced clear cell or non–clear cell renal cell carcinoma (RCC) with or without a sarcomatoid component. All patients had prior immunotherapy as the last line of therapy in the adjuvant, first-, or second line settings as a single agent or in combination with another agent.
A total of 522 patients were randomly assigned 1:1 to receive atezolizumab at 1,200 mg intravenously every 3 weeks with cabozantinib at 60 mg daily orally or cabozantinib alone. Stratification factors included International Metastatic RCC Database Consortium (IMDC) risk group, histology, and the most recent line of immune checkpoint inhibitor therapy. The most recent line of immune checkpoint inhibitor therapy was for front-line treatment in the locally advanced or metastatic setting in 52.9%; as second-line therapy in 46.4%; and as adjuvant therapy in a small number of patients (0.4%).
MORE INFORMATION
For more on the use of atezolizumab plus cabozantinib in the treatment of metastatic renal cell carcinoma from the CONTACT-03 trial, see a conversation with Rana R. McKay, MD, and Toni K. Choueiri, MD, on The ASCO Post Newsreels at ascopost.com/videos.
Most patients had dominant clear cell renal cell carcinoma without sarcomatoid histology (78.0%) vs non–clear cell renal cell carcinoma without sarcomatoid histology (11.7%) and any sarcomatoid histology (10.2%). A total 62.3% of patients had an IMDC score of 1 to 2 vs 22.6% with a score of 0 and 14.8% with a score of at least 3.
Adverse events led to treatment discontinuation in 15.6% of those on the doublet arm vs 3.9% of those on the monotherapy arm. Toxicities led to dose interruptions of atezolizumab in 60.7% of patients and of cabozantinib in 89.3% of those on the combination arm and 87.1% of those on the monotherapy arm.
DISCLOSURE: Dr. Choueiri reported financial and/or nonfinancial relationships (including potential reimbursements for travel and meals) with Alexion Pharmaceuticals, Alligent, Analysis Group, ASCO, AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, GlaxoSmithKline, Harborside, Heron, Ipsen, Kidney Cancer Journal, The Lancet Oncology, Eli Lilly, Lpath, Merck, Janssen, Michael J. Hennessy Associates, Navinata Healthcare, the National Comprehensive Cancer Network, The New England Journal of Medicine, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Sanofi/Aventis, and UpToDate; has received institutional research funding from Agensys, Analysis Group, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera Biosciences, Celldex, Cerulean Pharma, Congressionally Directed Medical Research Programs, Corvus Pharmaceuticals, Eisai, Exelixis, Foundation Medicine, Gateway for Cancer Research, GlaxoSmithKline, Ipsen, Merck, National Cancer Institute, Novartis, Peloton Therapeutics, Pfizer, Prometheus, Roche/Genentech, Seattle Genetics/Astellas, Takeda, and Tracon Pharma; holds international patents for biomarkers and has other relationships with ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, and Parexel (medical writing assistance); and holds stock or other ownership interests in Pionyr Immunotherapeutics and Tempest Therapeutics.
REFERENCES
1. Choueiri TK, Albiges L, Tomczak P, et al: Efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior immune checkpoint inhibitor treatment in metastatic renal cell carcinoma: Primary PFS analysis from the phase 3, randomized, open-label CONTACT-03 study. 2023 ASCO Annual Meeting. LBA4500. Presented June 4, 2023.
2. Pal S, Albiges L, Tomczak P, et al: Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): A multicentre, randomised, open-label, phase 3 trial. Lancet 402:P185-P195, 2023.
