ASCO 2019: CheckMate 214 Post-Hoc Analyses of Nivolumab plus Ipilimumab or Sunitinib in IMDC Intermediate/Poor-risk Patients with previously untreated Advanced Renal Cell Carcinoma with Sarcomatoid Features - Medical Oncologist Perspective

Chicago, IL ( Checkmate 214 was a large randomized phase III trial which compared nivolumab (nivo) plus ipilimumab (ipi) with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.1 Ipi/nivo was given with a four-dose induction period (once every three weeks) at a dose of Ipi 1 mg/kg and Nivo 3 mg/kg, followed by a maintenance period of nivolumab 3mg/kg every 2 weeks.   For patients in the intermediate or poor risk cohort, the 12-month overall survival (OS) rate was 80% (95% confidence interval [CI], 76 to 84) with nivolumab plus ipilimumab versus 72% (95% CI, 67 to 76) with sunitinib, (HR, 0.63; 99.8% CI, 0.44 to 0.89; P<0.001). At the 30 months follow up, which was presented at GU ASCO, OS remains significantly improved with ipi/nivo (NR vs 37.9, HR 0.71).2 This abstract provides data on patients who had tumors with sarcomatoid features.

112 patients had tumors with sarcomatoid features (sRCC) in CheckMate 214. Baseline characteristics are shown below.

ASCO 2019 checkmate 214 baseline characteristics

Sixty patients received ipi/nivo and 52 patients received sunitinib. 50% of sRCC had tumor PD-L1 expression ≥1% at baseline, which was almost twice as many patients compared to non-sRCC.

Patients with sRCC had significant higher ORR with ipi/nivo than with sunitinib (56.7% vs 19.2%, p<0.001) and the complete response rate was 18.3%.

ASCO 2019 checkmate 214 best overall response

Median overall survival was also improved, 31.2 months vs. 13.6 months (HR 0.55, p<0.001).

ASCO 2019 checkmate 214 overall survival

In terms of adverse events (AEs), the typical AEs associated with ipi/nivo were seen in the sarcomatoid group. The most common AEs were fatigue, diarrhea, nausea, pruritus, rash, and arthralgia.

For patients with mRCC with sarcomatoid features, Ipi/Nivo has an impressive complete response (CR) rate of 18.3%. The tumors in this population seem very sensitive to immune checkpoint inhibition, with a CR rate of 10% seen with pembrolizumab/axitinib. It is unknown which frontline therapy best balances toxicity with efficacy and at this time, both treatments are reasonable options for patients with mRCC with sarcomatoid features. Additional biomarker work is necessary to see if we can predict which patients respond better to dual CPI blockade vs. TKI/CPI blockade.

Presented by: David F. McDermott, MD, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu, at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine 2018;378:1277-90.
  2. Tannir NM, Frontera OA, Hammers HJ, et al. Thirty-month follow-up of the phase III CheckMate 214 trial of first-line nivolumab+ ipilimumab (N+ I) or sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). American Society of Clinical Oncology; 2019.