Anti-PD-1 Drug Improves Survival in NSCLC, Trial Halted

A study of nivolumab (Opdivo, Bristol-Myers Squibb) compared with docetaxel in patients with squamous cell non-small-cell lung cancer (NSCLC) was stopped early after an interim analysis showed superiority of the study drug. The study was conducted in patients with advanced disease receiving second-line therapy.

The open-label study, known as CheckMate 017, randomized 272 patients to either nivolumab 3 mg/kg intravenously every 2 weeks or to docetaxel 75 mg/m² IV every 3 weeks. The study is the first to ever indicate a survival advantage with an anti-PD1 immune checkpoint inhibitor in lung cancer, the company said in a press release. Data from the analysis will be shared with health authorities.

In late December, nivolumab received accelerated approval from the US Food and Drug Administration for the treatment of unresectable or metastatic melanoma following progression after ipilimumab treatment (and a BRAF inhibitor in BRAF V600 mutation-positive disease).

Targeting PD-1 has received substantial attention in recent years, and various drugs have begun to show promising results in this arena. Nivolumab is under investigation in a wide variety of malignancies-the CheckMate trials range across lymphoma, melanoma, colon cancer, renal cell carcinoma, glioblastoma, and others.

The accelerated approval granted for the melanoma indication came based on improvements in tumor response and durability of response. The NSCLC trial was stopped early after demonstrating improvements in overall survival. Secondary endpoints in the study included objective response rate and progression-free survival.

Though extensive data on adverse events (AEs) with nivolumab are not yet available in these NSCLC patients, the company noted that immune-mediated pneumonitis, colitis, hepatitis, nephritis, and other immune-mediated responses have all occurred with the drug. The most common AE with nivolumab, however, was rash, occurring in 21% of patients. Serious AEs occurred overall in 41% of patients receiving nivolumab, with the most frequent grade 3 and 4 AEs including abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.