FDA Approves Nivolumab (Opdivo) for Small Cell Lung Cancer

Nick Mulcahy

August 17, 2018

The US Food and Drug Administration (FDA) has approved nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of patients with metastatic small cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy, according to the company.

Nivolumab was granted accelerated approval for this indication on the basis of overall response rate and duration of response; as such, further proof of benefit in confirmatory trials may be required to establish full approval.

Until now, there have been no accepted or FDA-approved regimens for patients with SCLC whose disease has progressed after first- and second-line treatments, according to experts.

Nivolumab becomes the first new drug in nearly 20 years for this patient group, according to the company.

"Today's approval of nivolumab is particularly exciting, considering it is the first checkpoint inhibitor approved for these specific patients, and now we can finally treat this devastating disease from a different angle," said Leora Horn, MD, director of the thoracic oncology program, Vanderbilt University Medical Center in Nashville, Tennessee, in the company statement.

The approval was based on efficacy and safety data from the phase 1/2 CheckMate-032 trial. In that trial, 109 patients received nivolumab after platinum-based chemotherapy and at least one other prior line of therapy, and 12% responded (n = 13/109; 95% confidence interval [CI], 6.5 - 19.5).

Of the 13 patients who responded, 12 had a partial response (11%), and one had a complete response (0.9%). In this group, the median duration of response was 17.9 months (95% CI, 7.9 - 42.1; range, 3.0 - 42.1 months).

Patients received nivolumab 3 mg/kg by intravenous infusion over 60 min every 2 weeks until disease progression or unacceptable toxicity. The first tumor assessments were conducted 6 weeks after the first dose and were continued every 6 weeks for the first 24 weeks and every 12 weeks thereafter.

Nivolumab's safety was evaluated in the 245 patients with SCLC enrolled in the CheckMate trial who experienced disease progression after platinum-based chemotherapy. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions (≥2% of patients) were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.

The most common adverse reactions (≥20% of patients) were fatigue (45%), decreased appetite (27%), musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea (21%), constipation (20%), and cough (20%).

SCLC currently accounts for 14% of all lung cancers, or approximately 30,000 patients annually, according to a 2015 review article (Clin Cancer Res.2015;21:2244-55). Overall 5-year survival rates in the United States are a "dismal" 6%, according to the review authors, led by M. Catherine Pietanza, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York City.

These experts observe that first-line platinum-based chemotherapy for SCLC yields optimal tumor response rates as high as 60% to 80% but results in cure only in approximately 20% of patients with limited-stage SCLC. Most patients suffer relapse within months of completing initial therapy, according to the review authors. They also point out that topotecan (Hycamtin, Novartis) is the only FDA-approved agent for recurrent or progressive SCLC (ie, second-line treatment) and that as of 2015, no therapy had been accepted as standard after topotecan failure.

Nivolumab is also indicated for the treatment of patients with metastatic non–small cell lung cancer who experience disease progression during or after platinum-based chemotherapy. Patients who have EGFR or ALK genomic tumor aberrations should not receive nivolumab until they have experienced disease progression on FDA-approved therapy for these aberrations, according to the company.

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