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. 2021 Dec 15;27(24):6687-6695.
doi: 10.1158/1078-0432.CCR-21-2283. Epub 2021 Nov 10.

Treatment-free Survival after Immune Checkpoint Inhibitor Therapy versus Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of the CheckMate 214 Trial

Meredith M Regan  1   2 , Opeyemi A Jegede  3 , Charlene M Mantia  2   4 , Thomas Powles  5 , Lillian Werner  3 , Robert J Motzer  6 , Nizar M Tannir  7 , Chung-Han Lee  6 , Yoshihiko Tomita  8 , Martin H Voss  6 , Elizabeth R Plimack  9 , Toni K Choueiri  2   4 , Brian I Rini  10 , Hans J Hammers  11 , Bernard Escudier  12 , Laurence Albiges  12 , Stephen Huo  13 , Viviana Del Tejo  14 , Brian Stwalley  13 , Michael B Atkins  15 , David F McDermott  2   16
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Treatment-free Survival after Immune Checkpoint Inhibitor Therapy versus Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of the CheckMate 214 Trial

Meredith M Regan et al. Clin Cancer Res. .

Abstract

Purpose: Patients discontinuing immuno-oncology regimens may experience periods of disease control without need for ongoing anticancer therapy, but toxicity may persist. We describe treatment-free survival (TFS), with and without toxicity.

Patients and methods: Data were analyzed from the randomized phase III CheckMate 214 trial of nivolumab plus ipilimumab (n = 550) versus sunitinib (n = 546) for treatment-naïve, advanced renal cell carcinoma (aRCC). TFS was estimated by the 42-month restricted mean times defined by the area between Kaplan-Meier curves for two time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent systemic therapy initiation or death. TFS was subdivided as TFS with and without toxicity by counting days with ≥1 grade ≥3 treatment-related adverse event (TRAE).

Results: At 42 months since randomization, 52% of nivolumab plus ipilimumab and 39% of sunitinib intermediate/poor-risk patients were alive; 18% and 5% surviving treatment-free, respectively. Among favorable-risk patients, 70% and 73% of nivolumab plus ipilimumab and sunitinib patients were alive; 20% and 9% treatment-free. Over the 42-month period, mean TFS was over twice as long after nivolumab plus ipilimumab than sunitinib for intermediate/poor-risk (6.9 vs. 3.1 months) and three times as long for favorable-risk patients (11.0 vs. 3.7 months). Mean TFS with grade ≥3 TRAEs was a small proportion of time for both treatments (0.6 vs. 0.3 months after nivolumab plus ipilimumab vs. sunitinib for intermediate/poor-risk, and 0.9 vs. 0.3 months for favorable-risk patients).

Conclusions: Patients initiating first-line nivolumab plus ipilimumab for aRCC spent more survival time treatment-free without toxicity versus those on sunitinib, regardless of risk group.

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Figures

Figure 1. Characterizing how patients spent OS time: schematic illustration defining endpoints that partition area under the OS curve into TFS and other survival states. Areas under and between Kaplan–Meier curves are restricted mean times. The probability of surviving treatment-free (i.e., in TFS) at 42 months from randomization was estimated by the difference in Kaplan–Meier estimates of 42-month event-free times of the two defining endpoints (14). aTime after cessation of protocol therapy without toxicity, before initiation of subsequent systemic anticancer therapy, or death. bTime after cessation of protocol therapy with toxicity while treatment-free. cIncludes toxicity persisting since protocol therapy and toxicity newly presenting after protocol therapy cessation.
Figure 1.
Characterizing how patients spent OS time: schematic illustration defining endpoints that partition area under the OS curve into TFS and other survival states. Areas under and between Kaplan–Meier curves are restricted mean times. The probability of surviving treatment-free (i.e., in TFS) at 42 months from randomization was estimated by the difference in Kaplan–Meier estimates of 42-month event-free times of the two defining endpoints (14). aTime after cessation of protocol therapy without toxicity, before initiation of subsequent systemic anticancer therapy, or death. bTime after cessation of protocol therapy with toxicity while treatment-free. cIncludes toxicity persisting since protocol therapy and toxicity newly presenting after protocol therapy cessation.
Figure 2. Estimates of TFS, with and without toxicity, and other survival states over the 42-month period since randomization, according to treatment group, among 847 IMDC intermediate- and poor-risk patients. Toxicity is defined alternatively by grade ≥3 TRAEs (A) and grade ≥2 TRAEs (B). NIVO+IPI, nivolumab plus ipilimumab; Rx, therapy; SUN, sunitinib.
Figure 2.
Estimates of TFS, with and without toxicity, and other survival states over the 42-month period since randomization, according to treatment group, among 847 IMDC intermediate- and poor-risk patients. Toxicity is defined alternatively by grade ≥3 TRAEs (A) and grade ≥2 TRAEs (B). NIVO+IPI, nivolumab plus ipilimumab; Rx, therapy; SUN, sunitinib.
Figure 3. Estimates of TFS, with and without toxicity, and other survival states over the 42-month period since randomization, according to treatment group, among IMDC favorable-risk patients. Toxicity is defined alternatively by grade ≥3 TRAEs (A) and grade ≥2 TRAEs (B). NIVO+IPI, nivolumab plus ipilimumab; Rx, therapy; SUN, sunitinib.
Figure 3.
Estimates of TFS, with and without toxicity, and other survival states over the 42-month period since randomization, according to treatment group, among IMDC favorable-risk patients. Toxicity is defined alternatively by grade ≥3 TRAEs (A) and grade ≥2 TRAEs (B). NIVO+IPI, nivolumab plus ipilimumab; Rx, therapy; SUN, sunitinib.
Figure 4. Summary of estimated mean TFS and survival states over the 42-month period since randomization according to treatment group, in the overall intent-to-treat population and by IMDC subgroup. The total 42-month mean TFS, with and without toxicity, is indicated by the blue bracket. The height of the bars represents the 42-month mean overall survival. NIVO+IPI, nivolumab plus ipilimumab; Rx, therapy; SUN, sunitinib.
Figure 4.
Summary of estimated mean TFS and survival states over the 42-month period since randomization according to treatment group, in the overall intent-to-treat population and by IMDC subgroup. The total 42-month mean TFS, with and without toxicity, is indicated by the blue bracket. The height of the bars represents the 42-month mean overall survival. NIVO+IPI, nivolumab plus ipilimumab; Rx, therapy; SUN, sunitinib.
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