First Results of the Phase 3 CheckMate 9ER Trial - Episode 2
Toni Choueiri, MD: During the 2020 ESMO [European Society for Medical Oncology] virtual meeting, we were honored to take the plenary stage and present important results that could change how we treat kidney cancer again. It was one of the combinations that may become another option for patients with metastatic renal cell carcinoma who were previously untreated.
What did we present? We presented our initial results from the CheckMate 9ER study. This was a randomized phase 3 trial of over 650 patients who were randomized to sunitinib in the control arm vs the combination of cabozantinib plus nivolumab.
Cabozantinib is a VEGF tyrosine kinase inhibitor [TKI] also associated with activity against AXL and MET, which are known to be involved in angiogenesis resistance. The drug is already approved as a single agent for first-line and second-line metastatic renal cell cancer.
Nivolumab is a PD-1 inhibitor, and it is not a stranger in the renal cell cancer arena, since nivolumab is approved as a single agent post-VEGF TKI and in combination with ipilimumab in untreated patients.
All patient risk groups were included in this trial. The primary end point was progression-free survival [PFS]. The baseline characteristics were balanced between both arms; 23% of patients had favorable-risk disease, and interestingly enough, the progression-free survival was exactly double with the combination. That was the primary end point: 8.3 months, multiply that by 2, 16.6 months, with a hazard ratio of 0.51 for PFS. Equally if not more important, the secondary end point of overall survival was met with a hazard ratio of 0.6 and a 40% decrease in the chance of death with that combination. Response rates were doubled also, from 27% to over 55%. When you look at investigator-assessed PFS, it was longer at 19.4 months. This regimen has also been associated with the lowest incidence of PD [progressive disease] as best response.
What about safety? There were dose reductions: half of the patients needed dose reductions of both cabozantinib on the experimental arm and sunitinib on the control arm. If you look at the discontinuations of both drugs in the experimental arm due to treatment-related adverse events, it was less than 5%, and 8.8% with sunitinib. Overall, the toxicities were manageable. There was a slightly higher chance of liver function test abnormalities with the combination.
An important differentiator here in this combination is this: the authors were able to give us an idea about quality of life. We want patients to live longer; this was achieved in the CheckMate 9ER trial, but we want our patients to live better as well. To assess the quality of life, our patients reported outcomes through questionnaire. The study used 2 of them: the FKSI-19 [Functional Assessment of Cancer Therapy—Kidney Symptom Index, 19] and the FKSI-DRS [Functional Assessment of Cancer Therapy—Kidney Symptom Index, Disease-Related Symptoms]. Patients usually answered these questionnaires at each time point in each arm of the trial: the cabozantinib/nivolumab arm and the sunitinib arm.
Hands down, the quality of life statistical significance favored, in both questionnaires FKSI-19 and FKSI-DRS, the combination over sunitinib. Patients are not only living longer, they are also living better.
Transcript Edited for Clarity