While the methods of CheckMate 9ER have been previously presented and published, in brief, patients with advanced clear cell RCC were randomized in a 1:1 fashion to nivolumab 240 mg IV Q2W and cabozantinib 40 mg PO QD or sunitinib 50 mg PO QD (4 weeks of 6-week cycles). This presentation focused on a post hoc exploratory analysis in which PFS, OS, and ORR were examined across a number of subgroups defined by clinical characteristics including baseline IMDC risk status, organ sites of metastases, number of organs with any lesions, and target lesion size. RECIST v1.1 by blinded independent central review was used to assess PFS and ORR.
At the time of data cut-off, the median follow-up was 23.5 months.
To summarize, the authors found that progression-free survival was longer for patients who received nivolumab and cabozantinib, compared with sunitinib, across all subgroups examined, and, similarly, overall survival favored those who were treated with nivolumab and cabozantinib in all subgroups, though this effect was not significant in a number of subgroups on account of a wide confidence interval.
First assessing the effect of IMDC risk group on PFS, nivolumab and cabozantinib were associated better outcomes in patients with favorable risk (HR 0.58, 95% CI 0.36-0.93), intermediate-risk (HR 0.58, 95% CI 0.45-0.76), and poor-risk disease (HR 0.36, 95% CI 0.23-0.56). Assessing overall survival, the benefit of nivolumab and cabozantinib was statistically significant only among patients with poor-risk disease (HR 0.45, 95 CI 0.27-0.76).
In terms of organ site of metastasis, nivolumab and cabozantinib were associated with consistent improvements in both progression-free survival and overall survival for patients with liver, bone, and lung disease.
While PFS was improved for patients with 1 and 2+ sites of disease, overall survival was only improved in patients with 2+ sites of disease with a non-significant overall survival benefit in those with one site of disease (HR 0.79, 95% CI 0.33-1.90). A similar pattern emerged when examining the effect stratified by lesion size with a non-significant effect on overall survival seen in patients with small volumes of disease.
In terms of objective response rates, these were consistently higher for patients receiving nivolumab and cabozantinib.
Dr. Apolo concluded that the observed benefits of nivolumab and cabozantinib, compared to sunitinib, were consistent across many subgroups including those defined by IMDC risk group, site of metastasis, and extent of metastatic disease burden.
Presented By: Andrea B. Apolo, MD, Investigator Genitourinary Malignancies Branch NIH Lasker Clinical Research Scholar Head, Bladder Cancer Section, Center for Cancer Research National Cancer Institute, Bethesda, MD
Written By: Christopher J.D. Wallis, MD, Ph.D. Urologic Oncology Fellow, Vanderbilt University Medical Center, Twitter: @WallisCJD at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021