ESMO Virtual Congress 2020: Treatment-Free Survival, with and without Toxicity, after Immuno-Oncology vs. Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of CheckMate 214

(UroToday.com) The treatment landscape for first-line therapy among patients with metastatic renal cell carcinoma (mRCC) has changed dramatically over the past 2 years. In 2018, publication of the CheckMate214 data demonstrated a survival benefit for patients treated with nivolumab and ipilimumab compared with sunitinib in intermediate and poor-risk mRCC, ushering in the immunotherapy era for mRCC. The subsequent publication of the JAVELIN Renal 101 and KEYNOTE-426 studies in 2019 demonstrated the superiority of avelumab and axitinib and pembrolizumab and axitinib, compared to sunitinib in this disease space. These two trials were the first to demonstrate that the combination of immunotherapy with checkpoint inhibition and targeted therapy improved overall survival compared to sunitinib, the previous standard of care. Network meta-analysis following the publication of these data demonstrated the apparent superiority of this combined approach.


In a poster presentation at this year’s European Society of Medical Oncology (ESMO) 2020 Virtual Annual Meeting, Dr. Regan presented long-term results (42-months) of the CheckMate214 trial comparing nivolumab and ipilumumab to sunitinib, with a particular focus on treatment-free survival with and without toxicity.

The rationale for this approach is that conventional measure may not fully capture the effects on immuno-oncology (IO) approaches. Previous work has shown that patients may have long periods of disease control without subsequent anticancer therapy following discontinuation of IO regimes, and my experience toxicity during this time.

The authors utilized data from the CheckMate214 trial which randomized 1096 patients with advanced clear cell renal cell carcinoma in a 1:1 fashion to nivolumab 3mg/kg and ipilimumab 1mg/kg x 4 cycles followed by nivolumab or to sunitinib 50mg PO daily on a 4 week on / 2 week off schedule. In this analysis, the authors examined treatment free survival (TFS), defined as the time between protocol therapy cessation and subsequent systemic therapy or death. They then stratified this as TFS with or without toxicity by counting the number of days with ≥1 grade ≥3 treatment-related adverse events reported.

As of 42-months of follow-up, 56% of patients randomized to nivolumab/ipilimumab and 47% of those randomized to sunitinib were alive with 13% and 7%, respectively, remaining on their original therapy. A further 31% of patients randomized to nivolumab/ipilimumab and 12% of those randomized to sunitinib were surviving free of subsequent, second line therapy.

42-month restricted TFS was higher for patients randomized to nivolumab/ipilimumab (7.8 months) than those randomized to sunitinib (3.3 months). Toxicity-free TFS was 7.1 months and 3.0 months, respectively. In each case, the 95% confidence interval of the difference in median TFS excluded unity demonstrating that these are significant differences.

This effect was dramatic in both IMBC intermediate and poor risk disease (median TFS 6.9 vs 3.1 months) and favourable risk disease (median TFS 11.0 vs 3.7 months).

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Presented by: Meredith M. Regan, ScD, Researcher, Associate Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute.

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center (@WallisCJD on Twitter) at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020 


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ASCO GU 2020: Overall Survival and Independent Review of Response in CheckMate 214 with 42-month Follow-up: First-line Nivolumab + Ipilimumab versus Sunitinib in Patients with Advanced Renal Cell Carcinoma
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