Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: A pooled analysis Journal Article
| Authors: | Antonia, S. J.; Borghaei, H.; Ramalingam, S. S.; Horn, L.; De Castro Carpeño, J.; Pluzanski, A.; Burgio, M. A.; Garassino, M.; Chow, L. Q. M.; Gettinger, S.; Crinò, L.; Planchard, D.; Butts, C.; Drilon, A.; Wojcik-Tomaszewska, J.; Otterson, G. A.; Agrawal, S.; Li, A.; Penrod, J. R.; Brahmer, J. |
| Article Title: | Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: A pooled analysis |
| Abstract: | Background: Phase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival. Methods: We pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes. Trials of nivolumab in the second-line or later setting with at least 4 years follow-up were included. Comparisons of nivolumab versus docetaxel included all randomised patients from the phase 3 CheckMate 017 and 057 studies. We did landmark analyses by response status at 6 months to determine post-landmark survival outcomes. We excluded patients who did not have a radiographic tumour assessment at 6 months. Safety analyses included all patients who received at least one dose of nivolumab. Findings: Across all four studies, 4-year overall survival with nivolumab was 14% (95% CI 11–17) for all patients (n=664), 19% (15–24) for those with at least 1% PD-L1 expression, and 11% (7–16) for those with less than 1% PD-L1 expression. In CheckMate 017 and 057, 4-year overall survival was 14% (95% CI 11–18) in patients treated with nivolumab, compared with 5% (3–7) in patients treated with docetaxel. Survival subsequent to response at 6 months on nivolumab or docetaxel was longer than after progressive disease at 6 months, with hazard ratios for overall survival of 0·18 (95% 0·12–0·27) for nivolumab and 0·43 (0·29–0·65) for docetaxel; for stable disease versus progressive disease, hazard ratios were 0·52 (0·37–0·71) for nivolumab and 0·80 (0·61–1·04) for docetaxel. Long-term data did not show any new safety signals. Interpretation: Patients with advanced NSCLC treated with nivolumab achieved a greater duration of response compared with patients treated with docetaxel, which was associated with a long-term survival advantage. Funding: Bristol-Myers Squibb. © 2019 Elsevier Ltd |
| Keywords: | adult; cancer survival; controlled study; protein expression; aged; survival analysis; major clinical study; overall survival; fatigue; neutropenia; advanced cancer; diarrhea; drug safety; drug withdrawal; hypophosphatemia; outcome assessment; follow up; anemia; basal cell carcinoma; leukopenia; myalgia; peripheral neuropathy; cohort analysis; herpes zoster; drug effect; docetaxel; abdominal pain; arthralgia; asthenia; backache; coughing; dyspnea; lymphocytopenia; pneumonia; pruritus; rash; hypoxia; lung embolism; hyperkalemia; hyponatremia; survival time; clinical study; flank pain; pancreatitis; drug response; colitis; liver disease; interstitial lung disease; dermatitis; cancer control; encephalitis; pericardial effusion; anaphylaxis; disease exacerbation; bone necrosis; cerebrovascular accident; upper respiratory tract infection; hypocalcemia; heart tamponade; programmed death 1 ligand 1; non small cell lung cancer; adrenal insufficiency; randomized controlled trial (topic); bowen disease; decreased appetite; phase 3 clinical trial (topic); myositis; hypersensitivity; hypertransaminasemia; vasculitis; hyperamylasemia; diverticulitis; polyneuropathy; long term survival; body weight disorder; faintness; nivolumab; bullous dermatitis; human; male; female; priority journal; article; interstitial nephritis; neuromuscular junction disorder; joint effusion; rheumatic polymyalgia; uric acid stone |
| Journal Title: | Lancet Oncology |
| Volume: | 20 |
| Issue: | 10 |
| ISSN: | 1470-2045 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2019-10-01 |
| Start Page: | 1395 |
| End Page: | 1408 |
| Language: | English |
| DOI: | 10.1016/s1470-2045(19)30407-3 |
| PUBMED: | 31422028 |
| PROVIDER: | scopus |
| PMCID: | PMC7193685 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
