ECC 2015: Nivolumab Is More Effective Than Docetaxel in Extending Overall Survival in Advanced Nonsquamous NSCLC
A randomized phase III study by Borghaei et al evaluating the efficacy and safety of nivolumab (Opdivo) vs docetaxel in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) after failure of platinum-based chemotherapy has found that nivolumab improved overall survival, 12.2 months vs 9.4 months with docetaxel, representing a 27% lower risk of death with nivolumab. Among patients whose tumors expressed PD-L1 (programmed cell death ligand 1), nivolumab nearly doubled median overall survival compared with docetaxel. The study was presented at the European Cancer Congress 2015 (Abstract 3010) in Vienna, Austria, and was published in The New England Journal of Medicine.
Study Methodology
From November 2012 to December 2013, the researchers randomly assigned 582 patients into the study; 292 patients were assigned to receive nivolumab, and 290 patients were assigned to receive docetaxel. Of the 582 patients who underwent randomization, 287 were treated with nivolumab and 268 were treated with docetaxel. The minimum follow-up for overall survival was 13.2 months.
Eligible patients had either stage IIIB or IV or recurrent nonsquamous NSCLC following radiation therapy or surgical resection and also had disease recurrence or progression during or after one prior platinum-based regimen. Among the 582 patients, 455 had quantifiable PD-L1 expression. Rates of PD-L1 expression were balanced between the two groups.
Median age of the patients in the study was 62 years, and most patients were current or former smokers.
Study Findings
The researchers found that overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI] = 9.7–15.0) in the nivolumab group and 9.4 months (95% CI = 8.1–10.7) in the docetaxel group (hazard ratio [HR] = 0.73, 96% CI = 0.59–0.89, P = .002). At 1 year, the overall survival rate was 51% (95% CI = 45%–56%) with nivolumab vs 39% (95% CI = 33%–45%) with docetaxel.
With additional follow-up, the overall survival rate at 18 months was 39% (95% CI = 34%–45%) with nivolumab vs 23% (95% CI = 19%–28%) with docetaxel. The response rate was 19% with nivolumab vs 12% with docetaxel (P = .02). Although progression-free survival did not favor nivolumab over docetaxel (2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all endpoints in subgroups defined according to prespecified levels of tumor-membrane expression (≥ 1%, ≥ 5%, and ≥ 10%) of PD-L1.
Treatment-related adverse events of grades 3, 4, or 5 were reported in 10% of patients in the nivolumab group, as compared with 54% of those in the docetaxel group.
“Nivolumab led to a statistically superior survival benefit over docetaxel in unselected patients with advanced, previously treated nonsquamous non–small cell lung cancer,” concluded the researchers.
Hossein Borghaei, DO, of Fox Chase Cancer Center, is the corresponding author of The New England Journal of Medicine study.
The study was funded by Bristol-Myers Squibb. For full disclosures of the study authors, visit www.nejm.org.
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