(UroToday.com) The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer session included a presentation by Dr. Camillo Porta discussing subgroup analyses of the CheckMate 9ER trial assessing first-line nivolumab + cabozantinib versus sunitinib among patients with advanced RCC. Previously, first-line nivolumab + cabozantinib showed a significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus sunitinib in advanced RCC patients in the phase III CheckMate 9ER trial.1 On the basis of these results, the combination of nivolumab + cabozantinib was approved by the European Commission and FDA for the first-line treatment of advanced RCC. Patients without upfront nephrectomy have poor prognoses and clinical trial data in this population remain limited. Assessment of how different baseline characteristics may impact outcomes with nivolumab + cabozantinib versus sunitinib in advanced RCC patients is of clinical interest. In this exploratory post-hoc analysis of CheckMate 9ER, Dr. Porta and colleagues presented results assessing the efficacy of nivolumab + cabozantinib versus sunitinib in patients with subgroups defined by baseline nephrectomy status after a minimum follow-up of 16.0 months.
In this trial, patients with any IMDC risk and clear cell advanced RCC were randomized to nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD versus sunitinib 50 mg PO QD (4 weeks of 6-week cycles). In this post hoc exploratory analysis, efficacy was evaluated in subgroups with and without prior nephrectomy. PFS and ORR were assessed per RECIST v1.1 by blinded independent central review.
Of 651 intent-to-treat patients, 455 had prior nephrectomy (nivolumab + cabozantinib, n = 222; sunitinib, n = 233) and 196 had no prior nephrectomy (nivolumab + cabozantinib, n = 101; sunitinib, n = 95). Among patients with prior nephrectomy, 24.3% (nivolumab + cabozantinib) and 30.9% (sunitinib) underwent nephrectomy within 3 months of enrollment. Baseline characteristics were generally balanced between arms within subgroups. Versus patients without prior nephrectomy, a higher proportion of patients with prior nephrectomy had a lower tumor burden, more favorable IMDC risk scores, and derived greater efficacy benefits with either nivolumab + cabozantinib or sunitinib. Notably, nivolumab + cabozantinib improved PFS, ORR, complete response, and response durability outcomes versus sunitinib regardless of nephrectomy status:
Specifically, ORR among patients previously undergoing a nephrectomy was 60.8% (95% CI 54.1-67.3%) for those treated with nivolumab + cabozantinib compared to 30.5% (95% CI 24.6-36.8%) for sunitinib. For those without a prior nephrectomy, the ORR was 41.6% (95% CI 31.9-51.8%) for those treated with nivolumab + cabozantinib compared to 23.2% (95% CI 15.1-32.9%) for sunitinib. Of evaluable patients without prior nephrectomy, median reduction in target kidney lesions was 30% (nivolumab + cabozantinib; n = 53) versus 16% (sunitinib; n = 51). OS benefits were also observed with nivolumab + cabozantinib versus sunitinib in patients with prior nephrectomy, however longer follow-up is needed to characterize OS outcomes between arms in patients without prior nephrectomy.
Dr. Porta concluded his presentation of subgroup analyses of the CheckMate 9ER trial with the following summary statements:
- In this exploratory analysis, notable PFS and ORR benefits were observed with nivolumab + cabozantinib versus sunitinib regardless of prior nephrectomy status in CheckMate 9ER trial after a minimum follow-up of 16 months
- OS benefits with nivolumab + cabozantinib versus sunitinib were observed in patients with prior nephrectomy. Although OS probabilities at 12 and 18 months were higher with nivolumab + cabozantinib in the subgroup without prior nephrectomy, longer follow-up is needed to better characterize OS outcomes between treatment arms in this subgroup
- PFS, OS, and ORR benefits were observed with nivolumab + cabozantinib versus sunitinib in patients who underwent nephrectomy within 3 months of trial enrollment
- These data, together with ongoing prospective studies exploring the role of sequence of nephrectomy in patient with advanced RCC who receive systemic therapy, will continue to inform optimal advanced RCC treatment strategies
Presented by: Camillo Porta, MD, Department of Internal Medicine, University of Pavia, Pavia, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841.