Efficacy and safety of first-line (1L) nivolumab plus relatlimab (NIVO + RELA) versus NIVO plus ipilimumab (NIVO + IPI) in advanced melanoma: An updated indirect treatment comparison (ITC) with 4-year follow-up data.
Abstract
9554 Background: An ITC comparing NIVO + RELA and NIVO + IPI, approved dual immunotherapy treatment options for patients (pts) with advanced melanoma, was previously conducted using pt-level data from the pivotal RELATIVITY-047 (RELA-047; NIVO + RELA vs NIVO) and CheckMate 067 (CM-067; NIVO + IPI or NIVO vs IPI) trials (Long JCO 2024). Here we present updated results using 4-year follow-up data from RELA-047. Methods: Inverse probability of treatment weighting was used to adjust for cross-trial imbalances in baseline characteristics. CM-067 follow-up was truncated (median 41.0 mo) to best align with the follow-up length in RELA-047 (median 34.9 mo). Progression-free survival (PFS) per investigator, confirmed objective response rates (ORRs) per investigator, overall survival (OS), and melanoma-specific survival (MSS) were analyzed. Outcomes were also evaluated across key subgroups. The weighted NIVO arms from each trial were compared for internal validation. Results: After weighting, key baseline characteristics were balanced for NIVO + RELA (n=339) and NIVO + IPI (n=297). Outcomes after weighting were similar between NIVO + RELA and NIVO + IPI (hazard ratio [HR] [95% CI]: PFS 1.08 [0.89–1.33]; OS 0.95 [0.76–1.19]; table). Outcomes were similar between the NIVO arms, validating the ITC methodology. Across subgroups, efficacy appeared similar between treatments, although trends favoring NIVO + IPI were observed for ORR among pts with BRAF-mutant disease or serum lactate dehydrogenase >2x the upper limit of normal. Results when NIVO + IPI follow-up was untruncated were consistent with the truncated analyses. Conclusions: Consistent with previous results, this updated ITC with longer follow-up from RELA-047 suggests that 1L treatment with NIVO + RELA may have comparable efficacy to NIVO + IPI in pts with advanced melanoma, including most—but not all—subgroups. Results should be interpreted with caution given differences in study design and changes in the treatment landscape over time. Efficacy outcomes after weighting. NIVO + RELA (n = 339) NIVO + IPI (n = 297) HR/odds ratio [OR] (95% CI) NIVO RELA-047 (n = 338) NIVO CM-067 (n = 288) HR/OR (95% CI) Median PFS per INV, mo (95% CI) 12.0 (8.2–17.1) 11.2 (8.5–18.1) 1.08 (0.89–1.33) 6.6 (4.6–10.1) 5.7 (3.9–9.1) 0.96 (0.79–1.16) Confirmed ORR per INV, % 48 50 0.91 (0.73–1.14) 40 40 1.00 (0.79–1.28) Median OS, mo (95% CI) 64.5 (38.6–NR) NR (37.1–NR) 0.95 (0.76–1.19) 35.1 (27.3–48.8) 35.7 (26.4–NR) 1.02 (0.83–1.26) Median MSS, mo (95% CI) NR (NR–NR) NR (NR–NR) 0.87 (0.68–1.12) 51.2 (34.7–NR) 44.8 (32.3–NR) 0.96 (0.76–1.21) NR: not reached; HR/OR are NIVO+RELA vs NIVO+IPI.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (19)
Dirk Schadendorf
Hussein A. Tawbi
The University of Texas MD Anderson Cancer Center, Houston, TX
Evan J. Lipson
F. Stephen Hodi
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Paolo Antonio Ascierto
Università degli Studi di Napoli “Federico II” and Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
James Larkin
Christopher D. Lao
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Caroline Gaudy-Marqueste
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Jennell Palaia
Bristol Myers Squibb, Princeton, NJ
Viviana Garcia Horton
Analysis Group, Inc., New York, NY
Zheng-Yi Zhou
Analysis Group, Inc., New York, NY
Dana Christensen
Analysis Group, Inc., New York, NY
Hannah H Kim
Analysis Group, Inc., Boston, MA
Andriy Moshyk
Bristol Myers Squibb, Princeton, NJ
David R. D'Adamo
Bristol-Myers Squibb Co, Lawrenceville, NJ
Abraham Selvan
Bristol Myers Squibb, Princeton, NJ
Divya Patel
Leon A. Sakkal
Bristol Myers Squibb, Princeton, NJ
Georgina V. Long