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First-Line Monotherapy With Nivolumab (Anti-PD-1; BMS-936558, ONO-4538) in Advanced Non-Small Cell Lung Cancer (NSCLC): Safety, Efficacy, and Correlation of Outcomes With PD-L1 Status

2014; Elsevier BV; Volume: 90; Issue: 5 Linguagem: Inglês

10.1016/j.ijrobp.2014.08.204

1879-355X

Naiyer A. Rizvi, Frances A. Shepherd, Scott Antonia, Julie R. Brahmer, Laura Q.M. Chow, Jonathan W. Goldman, Rosalyn A. Juergens, Hossein Borghaei, Neal Ready, David E. Gerber, Yun Shen, Christopher Harbison, A.C. Chen, Scott Gettinger,

Peptidase Inhibition and Analysis

Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated durable responses and tolerability in heavily pretreated patients (pts) with advanced solid tumors, including NSCLC. This phase 1 study evaluated the safety and efficacy of nivolumab monotherapy as first-line treatment in a cohort of chemotherapy-naïve pts with advanced NSCLC, and examined tumor PD-1 ligand 1 (PD-L1) expression as a potential biomarker for nivolumab clinical activity. Pts (N=20) with squamous (sq) or non-sq advanced NSCLC received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity (postprogression treatment was permitted based on protocol-defined criteria). Responses were evaluated by RECIST 1.1 criteria. An analysis of response and progression-free survival (PFS) by tumor PD-L1 status (PD-L1+ defined as ≥5% tumor cells expressing PD-L1 [Dako immunohistochemistry assay]) was performed. All pts began study treatment ≥1 year prior to data analysis. Treatment-related grade 3-4 AEs were reported in 4 pts (20%), including increased AST or ALT, hyperglycemia, rash and cardiac failure (n=1 each). No pneumonitis (any grade) was observed. Objective response rate (ORR) was 30% (6/20; 22% in sq pts and 36% in non-sq pts); 2 confirmed CR, 1 unconfirmed CR; 5/6 responders (83%) achieved response by first scan (wk 11). Median duration of response (mDOR) was not reached (NR; range 23.7, 71.4+ wks); responses are ongoing in 4 pts (67%). Two pts had >80% target lesion reduction at 18 wks. One pt exhibited an unconventional response with 33% reduction in target lesions with simultaneous appearance of a new lesion. Median PFS was 36.1 wks (range 5.9, 80.7+ wks). The overall survival (OS) rate at 12 months was 75% (95% CI 50%, 89%); median OS was NR (range 13.3, 89.1+ wks). Tumor samples were sufficient for PD-L1 evaluation in 17 pts, of whom 10 were PD-L1+ and 7 were PD-L1-. ORR was 50% in pts with PD-L1+ tumors (mDOR NR); no responses were observed in pts with PD-L1- tumors. Median PFS was 45.6 wks and 36.1 wks for PD-L1+ and PD-L1- pts, respectively. First-line nivolumab demonstrated early, durable responses in chemotherapy-naïve pts with advanced NSCLC, with a tolerable safety profile. PD-L1 status appeared to correlate with ORR and PFS. Data will also be presented for 32 additional nivolumab-treated pts and a cohort of 12 prior treated pts with untreated brain metastases who received nivolumab monotherapy. These interim data support further studies of first-line nivolumab monotherapy in advanced NSCLC, and continued evaluation of PD-L1 status as a potential biomarker for nivolumab activity in NSCLC populations.