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At the European Society of Medical Oncology (ESMO) Virtual Congress 2020, Dr Choueiri from Dana Farber Cancer Institute in Boston, USA presented the results of the phase 3 CheckMate-9ER trial evaluating the combination of nivolumab and cabozantinib compared to sunitinib in the first-line treatment of patients with advanced or metastatic renal cell carcinoma (RCC).
Each of these treatments has proven survival benefit as single agents for metastatic RCC. CheckMate-9ER is a phase III, open-label, international randomised controlled trial in patients with previously untreated, advanced or metastatic clear cell RCC. Patients with sarcomatoid features were allowed.
Patients were randomised to receive either nivolumab intravenously every two weeks and oral cabozantinib daily or oral sunitinib daily for 4 weeks on and 2 weeks off. Randomisation was stratified by tumour risk score, the presence of tumour PD-L1 receptors, and region. Patients continued on the study until the disease progressed or there was unacceptable toxicity.
The primary outcome was progression-free survival. Secondary outcomes were overall survival, objective response rate, and safety/toxicity. A total of 651 patients were randomised, 323 to nivolumab plus cabozantinib and 328 to sunitinib. Of these patients, 22.6% had favourable risk disease, 57.6% had intermediate risk disease, and 19.7% had poor risk disease. Approximately one-quarter (24.9%) had PD-L1 expression >1%.
Median follow up was 18.1 months. Median progression-free survival was double among those randomised to nivolumab plus cabozantinib (16.6 months) than those randomised to sunitinib (8.3 months). Similarly, patients randomised to nivolumab plus cabozantinib had significantly longer overall survival than those receiving sunitinib.
Further, objective response rate was higher among patients receiving nivolumab plus cabozantinib (55.7%) than sunitinib (27.1%) and there were 8% complete responders in patients on nivolumab plus cabozantinib versus 4.6% for sunitinib. Median time to response was shorter and duration of response was longer among those receiving nivolumab plus cabozantinib.
Toxicity was similar in both groups but manageable. High grade events (severe or greater) were higher among those receiving nivolumab plus cabozantinib (60.6% vs 50.9%). Unfortunately, one patient died the nivolumab plus cabozantinib group while 2 died in the sunitinib treated group. Specific immune-related adverse events were noted in patients in the nivolumab/cabozantinib group, with 19% requiring corticosteroids to manage these events.
Dr Choueiri concluded that these data from CheckMate-9ER demonstrate the superiority of nivolumab plus cabozantinib to sunitinib in the first line treatment of patients with advanced RCC and support this approach as a new treatment option for these patients.