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LBA65 First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743

Abstract : Background In the randomized phase 3 CheckMate 743 study (NCT02899299), NIVO + IPI significantly prolonged overall survival (OS) vs chemo in pts with unresectable MPM. Here we report updated efficacy and safety with a 3-y minimum follow-up (f/u), as well as novel biomarker analyses. Methods Pts with untreated MPM, stratified by histology (epithelioid vs non-epithelioid) and sex, were randomized 1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W (≤ 2 y) or to chemo Q3W (6 cycles). The primary endpoint was OS; safety and biomarker assessments were prespecified exploratory endpoints. OS association with a 4-gene inflammatory gene expression signature (CD8A, PD-L1, STAT-1, LAG-3) was estimated by RNA sequencing and categorized as high vs low relative to median score. Lung immune prognostic index (LIPI) score was based on baseline (BL) derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels. Results With a minimum f/u of 35.5 mo (database lock [DBL] 7 May 2021), NIVO + IPI continued to provide OS benefit vs chemo (HR 0.75, 95% CI 0.63–0.90; Table). In exploratory biomarker analyses, median OS was longer for pts with high vs low inflammatory gene signature score (21.8 vs 16.8 mo) in the NIVO + IPI arm; this signature score was not associated with prolonged OS for chemo. OS showed a trend favoring NIVO + IPI vs chemo across good, intermediate, and poor BL LIPI subgroups; HR (95% CI), 0.78 (0.60–1.01), 0.76 (0.57–1.01), and 0.83 (0.44–1.57), respectively. Grade 3–4 treatment-related adverse events occurred in 30.7% (NIVO + IPI) and 32.0% (chemo) of pts; no increase was reported from the previous DBL. Table: LBA65 Efficacy outcomes with NIVO + IPI vs chemo NIVO + IPI (n = 303) Chemo (n = 302) OS Median (95% CI), mo 18.1 (16.8–21.0) 14.1 (12.4–16.3) HR vs chemo (95% CI) 0.75 (0.63–0.90) — 3-y OS rate (95% CI), % 23.2 (18.4–28.2) 15.4 (11.5–19.9) 3-y PFS a rate (95% CI), % 13.6 (9.4–18.6) 0.8 (0.1–3.9) ORR a (95% CI), % 39.6 (34.1–45.4) 44.0 (38.4–49.8) DOR a,b Median (95% CI), mo 11.6 (8.2–16.8) 6.7 (5.6–7.1) 3-y DOR rate, % 28 0 aPer blinded independent central review; bCalculated in patients with a response (NIVO + IPI, n = 120; chemo, n = 133). DOR, duration of response; ORR, objective response rate; PFS, progression-free survival. Conclusions With a 3-y minimum f/u, NIVO + IPI continued to provide survival benefit vs chemo in pts with unresectable MPM despite pts being off therapy for 1 y; no new safety signals were observed. Exploratory analyses suggest that a high inflammatory gene signature score may correlate with improved survival benefit with NIVO + IPI.
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Submitted on : Tuesday, March 29, 2022 - 5:59:43 PM
Last modification on : Tuesday, November 22, 2022 - 2:26:16 PM

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S. Peters, A. Scherpereel, R. Cornelissen, Y. Oulkhouir, L. Greillier, et al.. LBA65 First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743. Annals of Oncology, 2021, 32, pp.S1341-S1342. ⟨10.1016/j.annonc.2021.08.2146⟩. ⟨hal-03623619⟩

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