KEY TAKEAWAYS
- Phase 3 of CheckMate 214 trial was conducted to study the long-term efficacy and suitability of NIVO+IPI as a first-line treatment for patients with Untreated Advanced or Metastatic Renal Cell Carcinoma with Sarcomatoid features.
- 139 patients were randomized in an open-label trial to compare the NIVO+IPI combination with SUN monotherapy, where NIVO+IPI proved superior in terms of OS, PFS, and ORR.
- The minimum follow-up of Phase 3 was 5 years, in which the efficacy benefits of NIVO+IPI were maintained irrespective of the tumor PD-L1 expression. However, the magnitude of benefits was greater among tumor PD-L1 ≥ 1% of patients.
- No new safety signals were discovered in the longer follow-up.
In the CheckMate 214 study, Nivolumab plus Ipilimumab (NIVO+IPI) was explored as a first-line treatment and therapeutic option for patients with advanced RCC (renal cell carcinoma) with Sarcomatoid features (sRCC) with no prior treatments as an alternative to Sunitinib (SUN) treatment. Phase 3 of the study was an exploratory analysis with a minimum follow-up of 5 years to report the long-term efficacy of NIVO+IPI.
In this trial, 139 patients were identified with intermediate/poor-risk sRCC by reviewing the tumor tissue or as per the classification in the local pathology report. They were randomized into the two arms of the study, with the NIVO+IPI arm (n=74) receiving four doses of 3mg/kg NIVO with 1mg/kr IPI every 3 weeks, followed by 3mg/kg NIVO every 2 weeks. And the SUN arm (n=65) received a daily dose of 50mg SUN for 4 weeks in 6-week cycles.
The primary endpoints of the trial were the Overall Survival (OS), Progression-Free Survival (PFS), and Objective Response Rate (ORR) measured using the Response Evaluation Criteria in Solid Tumors V.1.1. The safety outcomes were reported based on the evaluation of these results.
The median OS of NIVO+IPI versus SUN was 48.6 vs 14.2 months (HR 0.46) at 5 years minimum follow-up. The median PFS and ORR were 26.5 vs 5.5 months (HR 0.50) and 60.8% vs 23.1%, respectively. 12% of the NIVO+IPI patients chose to remain on treatment at the 5 years data cutoff, while none of the SUN patients did so. The median DOR was longer with NIVO+IPI patients (not reached vs 25.1 months), with more patients completing responses (23.0% vs 6.2%). The OS, PFS, and ORR benefits of the NIVO+IPI treatment were greater among sRCC patients with tumor PD-L1 expression of ≥1%. However, NIVO+IPI remained superior irrespective of the tumor PD-L1 expression.
The primary results were supported in this 5 years follow-up data, demonstrating the superior long-term efficacy, durability, and tolerability of the NIVO+IPI combination over SUN as the preferred first-line therapy for previously untreated patients with intermediate/poor-risk sRCC.
Source Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791431/
Trial Link: https://clinicaltrials.gov/ct2/show/NCT02231749
Citation: Rini, B. I., Signoretti, S., Choueiri, T. K., McDermott, D. F., Motzer, R. J., George, S., Powles, T., Donskov, F., Tykodi, S. S., Pal, S. K., Gupta, S., Lee, C. W., Jiang, R., & Tannir, N. M. (2022). Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma. Journal for immunotherapy of cancer, 10(12), e005445. https://doi.org/10.1136/jitc-2022-005445
