FDA Approves Nivolumab, First Immunotherapy for Lung Cancer

Zosia Chustecka


March 04, 2015

Nivolumab (Opdivo, Bristol-Myers Squibb Company) is the first immunotherapy to be available for use in the treatment of lung cancer. The drug has just been approved by the US Food and Drug Administration (FDA) for use in patients with advanced/metastatic squamous non–small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

This is an additional indication for nivolumab; the drug was approved last year for patients with unresectable or metastatic melanoma who no longer respond to other drugs.

The approval of the lung cancer indication comes 3 months ahead of schedule, the FDA noted in its release.

It also noted that lung cancer is the leading cause of cancer death in the United States, with an estimated 224,210 new diagnoses and 159,260 deaths in 2014. NSCLC is the most common type of lung cancer, affecting 7 out of 8 lung cancer patients, the agency noted.

The approval is supported by results from a clinical trial that was stopped early after showing a survival benefit -- the manufacturer released this topline finding recently, but the clinical data have not yet been presented at a meeting or published. At the time, the company noted that that trial (known as CheckMate 017) was conducted in 272 patients with advanced or metastatic squamous cell NSCLC and that it was open label. Patients were randomly assigned to treatment with either nivolumab 3 mg/kg intravenously every 2 weeks or docetaxel 75 mg/m² intravenously every 3 weeks.

Now the FDA reveals that that trial was designed to measure overall survival (OS) and found that patients who received nivolumab lived 3.2 months longer than those who received docetaxel. In addition, the company now revealed that the median OS was 9.2 months in the nivolumab group (95% CI, 7.3 - 13.3) and 6 months in the docetaxel group (95% CI, 5.1, 7.3), showing a 41% reduction in the risk for death (hazard ratio, 0.59; 95% CI, 0.44 - 0.79; P = .00025).

This is the first time that an immunotherapy has shown a survival benefit in lung cancer, although there has been quite a bit of excitement at lung cancer meetings in the last 2 years over the potential for new immunotherapies in this disease, based on earlier findings.

Nivolumab is one of several new immunotherapies that act on the programmed death pathway -- it is a PD-1 inhibitor, and this action blocks the body's immune system from attacking cancerous cells, the FDA explained.

"The FDA worked proactively with the company to facilitate the early submission and review of this important clinical trial when results first became available in late December 2014," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "This approval will provide patients and healthcare providers knowledge of the survival advantage associated with nivolumab and will help guide patient care and future lung cancer trials."

The agency noted that the safety and efficacy of nivolumab in the treatment of squamous NSCLC were supported by a single-arm trial of 117 patients. These patients had progressed after receiving a platinum-based therapy and at least one additional systemic regimen, and were then treated with nivolumab. The results show that 15% of patients had an objective response rate, showing either partial shrinkage or complete disappearance of the tumor. Among the 15% who responded, more than half (59%) had responses lasting for 6 months or longer.

The most common side effects of nivolumab are fatigue, shortness of breath, musculoskeletal pain, decreased appetite, cough, nausea, and constipation. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys, and hormone-producing glands, the agency noted.

LUNGevity Foundation, a nonprofit organization, welcomed the approval of this "extraordinary" new drug with statements from two of its scientific advisory board members.

This is just the tip of the iceberg.

"Immunotherapy is transforming the lung cancer treatment paradigm, providing the most promising option yet in the second-line treatment for squamous cell lung cancer patients," said Julie Brahmer, MD, thoracic cancer director at the Johns Hopkins Kimmel Cancer Center and associate professor of oncology at Johns Hopkins in Baltimore. "There's still work to be done to determine which immunotherapy can best help which patient and which treatment combinations are most successful. The results of the nivolumab trials show the critical importance of lung cancer research and the extraordinary power of collaboration of researchers, physicians, and patients. The concurrence of patient and research interests has expedited the process behind this treatment from basic research to clinical trials to the initial step toward immunotherapy existing as the primary treatment for lung cancer. This is just the tip of the iceberg."

David Carbone, MD, PhD, director of the James Thoracic Center at The Ohio State University in Columbus, concurs. "The revolutionary new field of immunotherapy has completely transformed the way we treat and understand the disease. While not a panacea for everyone, immunotherapy is a quantum leap for lung cancer treatments, and will only show more promise as research continues to unveil innovative and exciting ways to tap the potential of this therapy."


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