Hospital Universitario Virgen Del Rocio, Sevilla, Spain
Luis Paz-Ares , Leora Horn , Hossein Borghaei , David R. Spigel , Martin Steins , Neal Ready , Laura Quan Man Chow , Everett E. Vokes , Enriqueta Felip , Esther Holgado , Fabrice Barlesi , Martin Kohlhaeufl , Oscar Rodriguez , Marco Angelo Burgio , Jerome Fayette , Scott N. Gettinger , Christopher Harbison , Friedrich Graf Finckenstein , Julie R. Brahmer
Background: Options for advanced non-SQ NSCLC patients (pts) who progress after platinum-based doublet chemotherapy (PT-DC) are limited, with minimal improvement in overall survival (OS). We report results from a randomized, global phase III study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n=292) or DOC 75 mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; Secondary objectives were investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression, quality of life, and safety. Results: NIVO demonstrated superior OS (HR=0.73; 96% CI: 0.59, 0.89; P=0.00155) and improved ORR (19.2% vs 12.4%; P=0.0235). HR for PFS was 0.92 (95% CI: 0.77, 1.11; P=0.393). PD-L1 expression was associated with benefit from NIVO (Table). In PD-L1+ pts, NIVO showed improved efficacy across all endpoints at predefined 1%, 5%, and 10% cut- points. Grade 3–5 drug-related AEs occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. No deaths were related to NIVO vs 1 DOC-related death. After discontinuation, 42.1% of NIVO and 49.7% of DOC pts received subsequent systemic therapy. Conclusions: NIVO demonstrated superior OS vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC. The safety profile of NIVO 3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase III trials. Clinical trial information: NCT01673867
Efficacy measure | NIVO (n=292) | DOC (n=290) | ||
---|---|---|---|---|
mOS, mo (95% CI) | 12.2 (9.7, 15.0) | 9.4 (8.0, 10.7) | ||
1-yr OS, % (95% CI) | 50.5 (44.6, 56.1) | 39.0 (33.3, 44.6) | ||
Median response duration, mo (95% CI) | 17.1 (8.4–not estimable) | 5.6 (4.4–7.0) | ||
mPFS, mo (95% CI) | 2.3 (2.2, 3.3) | 4.2 (3.4, 4.9) | ||
1-yr PFS, % (95% CI) | 18.5 (14.1, 23.4) | 8.1 (5.1, 12.0) | ||
m=median | ||||
PD-L1-quantifiable pts | ||||
PD-L1 expression | NIVO, n (N=231) | DOC, n (N=224) | OS HR (95% CI) | |
<1% | 108 | 101 | 0.9 (0.66, 1.24) | |
≥1% | 123 | 123 | 0.59 (0.43, 0.81) | |
<5% | 136 | 138 | 1.01 (0.76, 1.33) | |
≥5% | 95 | 86 | 0.43 (0.3, 0.63) | |
<10% | 145 | 145 | 1.00 (0.76, 1.31) | |
≥10% | 86 | 79 | 0.4 (0.27, 0.59) |
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