FDA Expands Approved Use of Nivolumab in Advanced Lung Cancer

Nivolumab demonstrates survival benefit in squamous and non-squamous non-small-cell lung cancer

On 9 October, 2015 the US Food and Drug Administration (FDA) approved nivolumab (Opdivo) to treat patients with advanced (metastatic) non-small-cell lung cancer (NSCLC) whose disease progressed during or after platinum-based chemotherapy. Opdivo works by targeting the cellular pathway known as PD-1/PD-L1. On 4 March 2015, the FDA approved Opdivo to treat patients with advanced squamous NSCLC whose disease progressed during or after platinum-based chemotherapy. Approval from 9 October expands the use of Opdivo to also treat patients with non-squamous NSCLC. 

The safety and effectiveness of Opdivo for this use was demonstrated in an international, open-label, randomised study of 582 participants with advanced NSCLC whose disease progressed during or after treatment with platinum-based chemotherapy and appropriate biologic therapy. Participants were treated with Opdivo or docetaxel. The primary endpoint was overall survival and the secondary endpoint was objective response rate. Those treated with Opdivo lived an average of 12.2 months compared to 9.4 months in those treated with docetaxel. Additionally, 19% of those treated with Opdivo experienced a complete or partial response, an effect that lasted an average of 17 months, compared to 12% among those taking docetaxel, which lasted an average of six months.

The results from the CheckMate 057 study were presented at the European Cancer Congress in Vienna, Austria and simultaneously published in the New England Journal of Medicine on 27 September 2015.

While patients who received Opdivo lived longer than those who received docetaxel across the study, an evaluation of samples from a subgroup of patients’ tumours suggests that the level of PD-L1 expression in NSCLC tumours may help identify patients who are more likely to live longer due to treatment with Opdivo. Therefore, the FDA also approved the PD-L1 IHC 28-8 pharmDx test to detect PD-L1 protein expression levels and help physicians determine which patients may benefit most from treatment with Opdivo.

The most common side effects of Opdivo are fatigue, musculoskeletal pain, decreased appetite, cough and constipation. Opdivo also has the potential to cause serious immune-mediated side effects that involve healthy organs, including the lung, colon, liver, kidneys, hormone-producing glands and the brain.  

The FDA granted Opdivo breakthrough therapy designation for this indication based on preliminary clinical evidence that suggested Opdivo may offer a substantial improvement over available therapies. It also received priority review status, which is granted to drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition.

The approval of Opdivo occurred approximately three months ahead of the prescription drug user fee goal date of 2 January 2016, the date when the agency was scheduled to complete its review of the application.

Another drug called pembrolizumab (Keytruda), manufactured by Merck, also targets the PD-1/PD-L1 pathway and was granted accelerated approval on 2 October 2015 for treating NSCLC specifically for patients whose tumours expressed PD-L1.

Opdivo is marketed by Bristol-Myers Squibb based in Princeton, New Jersey. The PD-L1 IHC 28-8 pharmDx test is marketed by Dako North America Inc. in Carpinteria, California.