KEY TAKEAWAYS
- The CheckMate 214 phase 3 trial aimed to investigate the long-term survival, response, and safety of 1L NIVO+IPI compared to sunitinib in patients with aRCC.
- Researchers noticed sustained survival and durable response benefits with NIVO+IPI over SUN, regardless of IMDC risk, with no new safety signals.
First-line (1L) nivolumab plus ipilimumab (NIVO+IPI) has provided substantial long-term survival benefits over sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC) in the CheckMate 214 trial.
With a median follow-up of 8 years—the longest follow-up to date for any phase 3 trial of immune checkpoint inhibitor combination therapy in patients with aRCC—they report survival, response per independent radiology review committee (IRRC), and safety in all randomized patients (intent-to-treat [ITT] population) and in patients with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable risk.
Michael B. Atkins and the team aimed to assess the long-term survival, response, and safety of 1L NIVO+IPI compared to sunitinib in patients with aRCC over an 8-year follow-up.
They performed an inclusive analysis in which patients with clear cell aRCC were randomized 1:1 to receive either NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks for 4 doses, followed by NIVO (3 mg/kg or 240 mg every 2 weeks or 480 mg every 4 weeks), or SUN 50 mg once daily for 4 weeks on, 2 weeks off.
Key study endpoints included overall survival (OS), IRRC-assessed progression-free survival (PFS), and objective response rate (ORR) in intermediate/poor-risk (primary), ITT (secondary), and favorable-risk (exploratory) patients. Cancer-specific survival was evaluated in ITT patients by censoring all causes of death other than RCC. Post hoc exploratory analyses in patients with favorable risk were also performed.
With 8 years (99.1 months) median follow-up, OS with NIVO+IPI vs SUN remained superior in ITT patients (hazard ratio [HR], 0.72). The HR for PFS with NIVO+IPI vs SUN was 0.88. ORR was higher with NIVO+IPI vs SUN, with more complete responses (CR) (12% vs 3%) and a longer median duration of response (DOR) in the combination arm vs SUN.
In patients with favorable risk, OS benefits were similar between arms (HR, 0.82). The HR for PFS favored SUN (HR, 1.76). ORR was lower with NIVO+IPI vs SUN, yet more patients achieved CR (13% vs 6%, respectively) and median DOR was longer with NIVO+IPI.
Median cancer-specific survival (95% CI) in ITT patients was 73.7 (62.8-91.2) months with NIVO+IPI vs 45.1 (37.8-53.3) months with SUN (HR, 0.69; 95% CI 0.59-0.82). In exploratory post hoc analyses of patients with favorable risk, 75/125 (60.0%) patients in the NIVO+IPI arm and 85/124 (68.5%) patients in the SUN arm died over 8 years of follow-up.
Of these patients, 31 in the NIVO+IPI arm and 27 in the SUN arm died within 3 years of randomization; the primary reason for death was disease in either arm (71.0% and 85.2%, respectively).
Furthermore, among 27 patients in the NIVO+IPI arm with favorable risk who died after disease progression within 3 years, 12 patients did not receive second-line (2L) systemic therapy. Beyond 3 years, only 2 of 43 patients who died after disease progression did not receive subsequent systemic therapy. Among all treated patients, incidence of any-grade and grade 3-4 treatment-related adverse events (AEs) remained largely unchanged. No new drug-related deaths occurred in either arm since the previous database lock.
The study concluded that NIVO+IPI demonstrates sustained survival benefits and more durable responses compared to SUN in the ITT population over an 8-year follow-up, with reduced risk of death measured by cancer-specific survival.
Long-term data in favorable-risk patients indicated improved OS HR, increased median DOR, and higher complete response rates (CRR) with NIVO+IPI vs SUN, contributing to OS and response benefits in the ITT group. Despite early challenges in patients with favorable risk, NIVO+IPI shows promise for long-term positive outcomes across different risk profiles, without new safety concerns emerging.
The trial was sponsored by Bristol-Myers Squibb.
Source: https://kcrs.kidneycan.org/wp-content/uploads/2024/06/KCRS24-Abstract-Book-6.27.24.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT02231749
Atkins MB, Escudier B, McDermott DF, et al. (2024). “Nivolumab plus ipilimumab vs sunitinib for first-line treatment of advanced renal cell carcinoma: 8-year follow-up with analyses in favorable risk patients from the phase 3 CheckMate 214 trial.” Presented at KCRS 2024, (Abstract 8)
