APHP Dermatology and CIC, U976, Université de Paris, Hôpital Saint-Louis, Paris, France
Celeste Lebbe , Nicolas Meyer , Laurent Mortier , Ivan Marquez-Rodas , Caroline Robert , Piotr Rutkowski , Marcus O. Butler , Thomas Eigentler , Alexander M. Menzies , Michael Smylie , Ana Maria Arance , Paolo Antonio Ascierto , Inge Marie Svane , Mazhar Ajaz , Nikhil I. Khushalani , Maurice Lobo , Jesus Zoco , Jacopo Pigozzo
Background: NIVO 1 mg/kg plus IPI 3 mg/kg (NIVO1 + IPI3) is approved for treatment (tx) of unresectable/adv melanoma, with demonstrated durable clinical benefit on long-term follow-up. Analysis of the phase 3b/4 CheckMate 511 study (NCT02714218) at 1 y showed that NIVO 3 mg/kg plus IPI 1 mg/kg (NIVO3 + IPI1) improves the safety profile of the combination; efficacy with the 2 regimens was similar in descriptive analyses. Here we present 3-y safety/efficacy results. Methods: Patients (pts) ≥ 18 y of age with previously untreated unresectable stage III/IV melanoma were randomized 1:1 to receive NIVO3 + IPI1 Q3W × 4 (N = 180) or NIVO1 + IPI3 Q3W × 4 (N = 178), both followed by NIVO 480 mg Q4W until progression/unacceptable toxicity. The primary endpoint was the incidence of grade (gr) 3–5 tx-related adverse events (TRAEs); secondary endpoints (descriptive analyses) included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The study was not powered to formally demonstrate noninferiority for efficacy endpoints. Results: At a median follow-up of 44.4 and 43.9 mo in the NIVO3 + IPI1 and NIVO1 + IPI3 groups, respectively, TRAEs led to tx discontinuation in 26% and 39% of pts; 57% and 42% of pts had received maintenance therapy. Gr 3–5 TRAE incidence remained significantly lower with NIVO3 + IPI1 than NIVO1 + IPI3 (33.9% vs 48.3%; odds ratio 0.55 [95% CI 0.36–0.84]). The most frequent TRAEs (any gr) were diarrhea (27%), fatigue (26%), and pruritus (26%) with NIVO3 + IPI1 and diarrhea (31%), pruritus (29%), and rash (27%) with NIVO1 + IPI3. In descriptive analyses, efficacy results were similar to those observed at 1 y. OS and tx-free–analysis outcomes were numerically similar in the 2 groups (table). Conclusions: At 3-y follow-up, NIVO3 + IPI1 continued to demonstrate an improved safety profile compared with NIVO1 + IPI3. In descriptive analyses, both groups demonstrated high 3-y OS rates that were numerically similar. This study provides important information regarding the benefit–risk profile of both dosing regimens of NIVO + IPI in pts with adv melanoma. Clinical trial information: NCT02714218
Secondary endpoints | NIVO3 + IPI1 (N = 180) | NIVO1 + IPI3 (N = 178) | Stratified HRa (95% CI) |
---|---|---|---|
Investigator-assessed ORR, % (95% CI) | 47 (40–55) | 53 (45–60) | 0.80b (0.53–1.21) |
mPFS, mo (95% CI) | 10.2 (6.2–21.9) | 10.0 (6.3–40.9) | 1.13 (0.85–1.50) |
36-mo PFS rate, % (95% CI) | 38 (30–46) | 43 (35–50) | – |
mOS, mo (95% CI) | NR (43.7–NR) | NR (40.8–NR) | 1.03 (0.75–1.41) |
36-mo OS rate, % (95% CI) | 59 (51–66) | 61 (53–67) | – |
mTFI,c,d mo (range) | 21.1 (0.2–48.9)e | 22.6 (0.1–50.6)f | – |
Pts alive and tx-free,d,g n (%) | 72 (74) | 72 (77) | – |
aNIVO3 + IPI1 vs NIVO1 + IPI3. bOdds ratio. cTime from end of tx until subsequent cancer tx or last known date alive (if no subsequent cancer tx was received). dPost hoc analysis. en = 132. fn = 127. gPts free of study tx and subsequent systemic tx among those alive and in follow-up at database lock (n = 97 and 94). m, median; NR, not reached; TFI, tx-free interval.
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