FDA Expands Use of Nivolumab in Lung Cancer

Nick Mulcahy


October 09, 2015

The US Food and Drug Administration (FDA) today expanded the approved use of nivolumab (Opdivo, Bristol-Myers Squibb) to include the treatment of patients with metastatic nonsquamous, non-small-cell lung cancer (NSCLC) whose disease progressed during or after platinum-based chemotherapy.

Earlier this year, nivolumab was approved for use in advanced squamous NSCLC, with the same conditions about disease progression.

Nivolumab works by targeting the programmed death (PD) pathway and releasing the body's immune system to fight the cancer cells. Clinical research has established that PD-1 inhibition works best in the setting of high PD-ligand 1 (L1) tumor expression.

Thus, the FDA also approved today the PD-L1 IHC 28-8 pharmDx test to detect PD-L1 protein expression levels and help physicians determine which patients would likely benefit most from the drug treatment.

"While nivolumab showed an overall survival benefit in certain non-small-cell lung cancer patients, it appears that higher expression of PD-L1 in a patient's tumor predicts those most likely to benefit," Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research, said in a press statement.

The new approval is based on results from the CheckMate 057 study, conducted in 582 patients with advanced nonsquamous NSCLC who had progressed on platinum-doublet chemotherapy. The overall results showed that median overall survival was about 3 months longer with nivolumab than with docetaxel (12.2 vs 9.4 months; hazard ratio, 0.73; P = .0015).

However, a subset of patients with high levels of PD-L1 expression derived even greater benefit; here, median overall survival ranged from 17.2 to 19.4 months.

When these data were presented earlier this year, investigator Luis Paz-Ares MD, PhD, from the Hospital Universitario Virgen Del Roccio in Seville, Spain, said this survival benefit was unprecedented in this patient population.

In the pivotal trial, response rates were higher in the full set of patients treated with nivolumab than in those treated with docetaxel (19.2% vs 12.4%). Median response also lasted significantly longer in the nivolumab group (17.1 vs 5.6 months).

The most common adverse effects of nivolumab are fatigue, musculoskeletal pain, decreased appetite, cough, and constipation. Notably, the drugs can also cause serious immune-mediated adverse effects in the lung, colon, liver, kidneys, hormone-producing glands, and the brain.

This approval of nivolumab occurred approximately 3 months ahead of the FDA's public schedule.

Last week, the FDA approved another PD-1 inhibitor, pembrolizumab (Keytruda, Merck), for the treatment of patients with NSCLC whose tumors express PD-L1. The same companion diagnostic test was also approved.


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