Long-term survival in advanced melanoma for patients treated with nivolumab plus ipilimumab in CheckMate 067.
F. Stephen Hodi, Vanna Chiarion‐Sileni, Karl D. Lewis, Jean‐Jacques Grob, Piotr Rutkowski, Christopher D. Lao, C. Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Paola Queirolo, Michael Smylie, Marcus O. Butler, Andrew Hill, Iván Márquez‐Rodas, John B.A.G. Haanen, Piyush Durani, Peter Wang, Jedd D. Wolchok, James Larkin
Abstract
9522 Background: Durable clinical benefit has been achieved with nivolumab (NIVO) + ipilimumab (IPI), including an overall survival (OS) of 49% and a melanoma-specific survival (MSS) of 56%, with median MSS not reached (NR) at 6.5-y minimum follow-up. Here we report sustained efficacy outcomes at 7.5 y. Methods: Patients (pts) with previously untreated, unresectable stage III/IV melanoma were randomly assigned 1:1:1 and stratified by PD-L1 status, BRAF mutation status, and metastasis stage to receive NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W, followed by NIVO 3 mg/kg Q2W (n = 314); NIVO 3 mg/kg Q2W + placebo (n = 316); or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were progression-free survival (PFS) and OS with NIVO + IPI or NIVO alone versus IPI. Results: With a minimum follow-up of 7.5 y, median OS remained stable at 72.1 mo (NIVO + IPI), 36.9 mo (NIVO), and 19.9 mo (IPI); median MSS was NR, 49.4 mo, and 21.9 mo, respectively (Table). While the objective response rate remained stable at 58% (NIVO + IPI), 45% (NIVO), and 19% (IPI), median duration of response had now been reached for NIVO at 90.8 mo and remains NR and 19.2 mo for NIVO + IPI and IPI, respectively. Subsequent systemic therapy was received by 36%, 49%, and 66% of NIVO + IPI-, NIVO-, and IPI-treated patients, respectively, and median time to that therapy was NR (95% CI, 45.9–NR), 24.7 mo (16.0–38.7), and 8.0 mo (6.5–8.7). Of patients alive at 7.5 y, 106/138 (77%, NIVO + IPI), 80/115 (70%, NIVO), and 27/60 (45%, IPI) were off treatment and had never received subsequent systemic therapy. No change to the safety summary was observed with additional follow-up; updated health-related quality of life data will be reported. Of the 10 new deaths since the 6.5-y follow-up (ie, 5 NIVO + IPI; 3 NIVO; 2 IPI), none were treatment-related; 4 were due to melanoma progression; 1 was due to an unknown cause; and 5 were due to other causes, but not associated with a COVID diagnosis. Conclusions: The 7.5-y follow-up continues to demonstrate the durability of responses with NIVO + IPI and an ongoing survival plateau. A substantial difference in median OS and MSS between patients treated with NIVO + IPI or NIVO was observed in descriptive analyses. Clinical trial information: NCT04540705. [Table: see text]