First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial

Abstract

We present an exploratory post hoc analysis from the phase 3 CheckMate 214 trial of first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) without prior nephrectomy and with an evaluable primary tumor, a population under-represented in clinical trials. Patients with clear cell aRCC were randomized to NIVO+IPI every 3 wk for four doses followed by NIVO monotherapy, or sunitinib every day for 4 wk (6-wk cycle). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and primary tumor shrinkage were assessed. PFS and ORR were assessed per independent radiology review committee using RECIST version 1.1. With minimum study follow-up of 4 yr for intent-to-treat patients, OS favored NIVO+IPI (n = 53) over sunitinib (n = 55; hazard ratio 0.63, 95% confidence interval 0.40-1.0) among patients without prior nephrectomy. ORR was higher (34% vs 15%; p = 0.0041) and median duration of response was longer with NIVO+IPI versus sunitinib (20.5 vs 14.1 mo); the best overall response was partial response in either arm. A ≥30% reduction in the diameter of intact target renal tumors was achieved in 35% of patients with NIVO+IPI versus 20% with sunitinib. Safety was consistent with the global study population. In conclusion, in patients with aRCC without prior nephrectomy and with an evaluable primary tumor, NIVO+IPI showed survival benefits and renal tumor reduction versus sunitinib. This trial is registered at ClinicalTrials.gov as NCT02231749. PATIENT SUMMARY: In an exploratory analysis of a large global trial (CheckMate 214), we observed positive outcomes (both survival and tumor response to treatment) with nivolumab plus ipilimumab over sunitinib in a subgroup of patients with advanced kidney cancer who did not undergo removal of their primary kidney tumor. This subset of patients represents a population that has not been studied in clinical trials and for whom outcomes with new immunotherapy combination regimens are not yet known. We conclude that treatment with nivolumab plus ipilimumab offers these patients a survival benefit versus sunitinib, consistent with that observed in the overall study, as well as a notable kidney tumor reduction.

Keywords: Advanced renal cell carcinoma; CheckMate 214; Cytoreductive nephrectomy; Ipilimumab; Nivolumab.

Fig. 1 –

Kaplan-Meier curves for (A) OS ^a and (B) PFS per IRRC using RECIST version 1.1 ^b in patients without prior nephrectomy and with an evaluable primary tumor, and (C) maximum reduction in target renal tumors in all response-evaluable patients without prior nephrectomy and with an evaluable primary tumor. ^c–g BOR = best overall response; CI = confidence interval; HR = hazard ratio; IRRC = independent radiology review committee; NIVO + IPI = nivolumab plus ipilimumab; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors; SUN = sunitinib. ^a Median (95% CI) OS was 26.1 (14–35) mo with NIVO + IPI versus 14.3 (9.7–23) mo with SUN (HR 0.63, 95% CI 0.40–1.0); there were 37 events/53 patients versus 44 events/55 patients, respectively. ^b Median (95% CI) PFS was 8.1 (5.5–21) mo with NIVO + IPI versus 11.9 (8.4–18) mo with SUN (HR 0.99, 95% CI 0.59–1.7); there were 33 events/53 patients versus 29 events/55 patients, respectively. ^c Patients with a primary tumor at baseline and one or more on-treatment tumor assessments were included. ^d Of the 108 patients without nephrectomy, 49/53 patients in the NIVO + IPI arm and 41/55 patients in the SUN arm had a primary tumor at baseline and one or more on-treatment tumor assessments. ^e Two patients (3.8%) patients in the NIVO + IPI arm versus three (5.5%) in the SUN arm had more than one evaluable target renal tumor. ^f Best reduction shown is the maximum reduction in the sum of the diameters of target renal tumors (a negative value indicates a true reduction; a positive value indicates an increase only observed over time). The horizontal reference line at +20% indicates a 20% increase and the horizontal reference line at −30% indicates a 30% reduction, both consistent with a RECIST version 1.1 response. ^g Different colored bars represent overall systemic responses (including but not limited to responses in the primary tumor) according to RECIST version 1.1.