Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): Survival and clinical activity by subgroup analysis.
2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2014.32.15_suppl.8112
ISSN1527-7755
AutoresJulie R. Brahmer, Leora Horn, Leena Gandhi, David R. Spigel, Scott Antonia, Naiyer A. Rizvi, John D. Powderly, Rebecca S. Heist, Richard D. Carvajal, David M. Jackman, Lecia V. Sequist, David C. Smith, Philip D. Leming, Suzanne L. Topalian, F. Stephen Hodi, Mario Sznol, Christopher Harbison, Georgia Kollia, Ashok Gupta, Scott Gettinger,
Tópico(s)Hepatocellular Carcinoma Treatment and Prognosis
Resumo8112^ Background: Nivolumab, a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in a large phase I trial of pts with advanced solid tumors. For NSCLC pts in this trial, we report overall survival (OS) by dose and histology and clinical activity of pt subgroups including PD-L1 tumor status. Methods: Previously treated pts with advanced NSCLC received IV nivolumab (1, 3, or 10 mg/kg) Q2Wk for ≤96 wk with tumor evaluation by RECIST v1.0. Clinical activity by key prognostic factors was assessed. PD-L1 tumor cell membrane expression was measured in archival specimens (n=68) by a Dako immunohistochemistry assay (positive ≥5% tumor cells). Results: Across doses and histologies, NSCLC pts (N=129, 54% with ≥3 prior therapies) hadmedian overall survival (mOS) of 9.2-14.9 mo and 1- and 2-y OS rates of 32-56% and 12-45%, respectively (Table). At the 3 mg/kg dose, mOS was 14.9 mo; 1- and 2-y OS rates were 56% and 45%. Objective response rate was 17% (22/129); median response duration was 17 mo. Clinical activity was observed across all pt subgroups, including <3 and ≥3 prior therapies and with/without EGFR or KRAS mutations. For pts with PD-L1(+) and (–) tumors, mOS was 7.8 mo (95% CI: 5.6, 21.7) and 10.5 mo (5.2, 21.2), respectively; mPFS was 3.6 mo (1.8, 7.5) and 1.8 mo (1.7, 2.3). Grade 3-4 treatment-related adverse events occurred in 14% of pts; most common was fatigue (3%). Conclusions: Nivolumab continues to demonstrate an encouraging survival profile and clinical activity across NSCLC pt subgroups with a manageable safety profile. Ongoing phase III trials are evaluating 3 mg/kg nivolumab in NSCLC pts and PD-L1 as a potential predictor of clinical outcomes. Clinical trial information: NCT00730639. Pts mOS,* mo (95% CI) OS rate,* % (95% CI) [pts at risk] 1-Y 2-Y All† n=129 9.9 (7.8, 12.4) 42 (34, 51) [48] 24 (16, 32) [20] 1 mg/kg n=33 9.2 (5.3, 11.1) 32 (16, 49) [8] 12 (3, 27) [2] 3 mg/kg n=37 14.9 (7.3, NR) 56 (38, 71) [17] 45 (27, 61) [9] 10 mg/kg n=59 9.2 (5.2, 12.4) 40 (27, 52) [23]) 19 (10, 31) [9] Squamous n=54 9.2 (7.3, 12.5) 40 (27, 54) [19] 24 (13, 37) [9] Nonsquamous n=74 10.1 (5.7, 13.7) 43 (32, 54) [28] 23 (13, 34) [10] Abbreviation: NR, not reached. *Sept 2013 analysis. †One pt had unknown histology.
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