Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).

Abstract

609 Background: N+I demonstrated superior OS and ORR v S in intention-to-treat (ITT) and intermediate/poor-risk (IP) pts with aRCC in CheckMate 214. Here, we report OS, response outcomes per independent radiology review committee (IRRC), and safety with extended min follow-up of 42 mo. Methods: Pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3W×4 and then N 3 mg/kg Q2W, or S 50 mg daily for 4 wk on, 2 wk off. Endpoints were OS, ORR, and PFS per IRRC using RECIST v1.1 in IP (primary), ITT (secondary), and favorable pts (FAV; exploratory). Results: OS remained superior in ITT (HR 0.72) and IP (HR 0.66) pts with N+I v S (Table). ORR per IRRC was higher and more responses were ongoing with N+I v S (68% v 53% [ITT] and 68% v 52% [IP]). More pts achieved complete response (CR) with N+I and these were ongoing in 86% [ITT] and 84% [IP] of pts. The PFS probability with N+I stabilized after 24 mo at ~35% in ITT and IP pts, whereas probabilities declined over time with S. Among FAV pts, while ORR was 29% with N+I v 54% with S, more pts achieved CR (13% v 6%), and more responses were ongoing (69% v 54%) with N+I v S; 94% of CRs in FAV pts were ongoing with N+I. OS benefits were similar in both arms and PFS probabilities are stabilizing with N+I and declining with S in FAV pts. The incidence of any and grade 3–4 treatment-related AEs was consistent with previous reports and no new drug-related deaths occurred in either arm. Response outcomes per investigator will also be reported. Conclusions: Superior OS and ORR with N+I v S was maintained in ITT and IP pts. More pts treated with N+I experienced CR compared with S, responses and CRs were durable, and PFS probabilities stabilized with N+I after extended follow-up. No new safety signals emerged. Clinical trial information: NCT02231749 .[Table: see text]

Anti-Angiogenesis and Immunotherapy: Novel Paradigms to Envision Tailored Approaches in Renal Cell-Carcinoma

“…favorable-risk participants established sunitinib to be more active when compared to ICI in this patient subset, gaining a median PFS of 27.7 vs. 17.8 months and ORRs of 54% vs. 29% [101]. However, the clinical and pathological features, not entirely mirroring the complex biology of the tumor should be adapted to the novel agents´ era.…”

“…PFS= progression free survival; OS= overall survival; ORR= overall response rate; CR= complete response; AE= adverse events; NA= not available; NR = not reached. [49,50,95,98,106]…”

Advanced renal cell carcinoma (RCC) management: an expert panel recommendation from the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG)

“…In this population, the ORR (42% and 26%; p < 0.0001) and the OS (47.0 vs 26.6 months; p = 0.0001) were also better in the nivolumab plus ipilimumab group than in the sunitinib group. The complete response rate was also significantly different between the groups (10% in nivo ipi arm versus 1% in sunitinib arm group; p = 0.01) (Tannir et al 2020). The first analysis in the subgroup of favorablerisk patients suggested improved OS and progression-free survival (PFS) rates with sunitinib as compared to ipi/nivo (Motzer et al 2018a, b), but after extended follow-up of 32.4 and 42 months, this difference was no longer statistically significant (Motzer et al 2019a, b;Tannir et al 2020).…”

“…The complete response rate was also significantly different between the groups (10% in nivo ipi arm versus 1% in sunitinib arm group; p = 0.01) (Tannir et al 2020). The first analysis in the subgroup of favorablerisk patients suggested improved OS and progression-free survival (PFS) rates with sunitinib as compared to ipi/nivo (Motzer et al 2018a, b), but after extended follow-up of 32.4 and 42 months, this difference was no longer statistically significant (Motzer et al 2019a, b;Tannir et al 2020). On the other hand, the combination of pembrolizumab plus axitinib significantly improved OS, PFS and response rate as first-line treatment compared with sunitinib in patients with all IMDC risk groups, regardless of PD-L1 expression, according to the results of study KEYNOTE-426 (Powles et al 2019a, b).…”

Interdisziplinäre Empfehlungen zur Behandlung des fortgeschrittenen Nierenzellkarzinoms

“…Bei einer Nachbeobachtungszeit von 42 Monaten betrug das mediane OS unter Nivolumab + Ipilimumab 47,0 Monate im Vergleich zu 26,6 Monaten im Vergleichsarm (HR = 0,66; p < 0,0001). 52 % der Kombinations-Patienten und 39 % der TKI-Patienten waren noch am Leben [32].…”