FDA Approves Presurgical, Postsurgical Opdivo for NSCLC

The Food and Drug Administration (FDA) has approved neoadjuvant (presurgical) Opdivo (nivolumab) with platinum-doublet chemotherapy followed by postsurgical single-agent Opdivo for adults with resectable (removable by surgery) tumors at least 4 centimeters and/or node-positive disease non-small cell lung cancer (NSCLC) and no known EGFR mutations or ALK rearrangements, the agency has announced.

The effectiveness of the treatment was observed in the CHECKMATE-77T clinical trial of 461 patients with previously untreated and resectable stage 2A to stage 3B NSCLC. Patients in the trial received either Opdivo or placebo with platinum-based chemotherapy every three weeks for up to four cycles, followed after surgery by either single-agent Opdivo or placebo every four weeks for up to 13 cycles.

Median event-free survival (the time a patient lives without disease worsening or complications) was not reached (meaning it occurred in less than half of patients) in the Opdivo arm and 18.4 months in the chemotherapy arm. At the time of the interim analysis, overall survival (the time a patient lives regardless of disease status) was not tested for statistical significance, but the FDA reported that a descriptive analysis showed no detriment.

Opdivo, according to a news release from manufacturer Bristol Myers Squibb, is the only PD-1 inhibitor shown to demonstrate statistically significant and clinically meaningful benefits in this disease versus chemotherapy in both the presurgical-only setting and as part of a regimen before and after surgery.

“Given the rates of disease recurrence in patients with resectable NSCLC, there is a clear need for options that can be administered before and after surgery that may target micrometastasis, help reduce the risk of cancer returning and improve the chance of successful surgical treatment,” said Dr. Tina Cascone, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, in the news release. “This approval is a step forward for patients with resectable disease, as the perioperative [Opdivo] plus neoadjuvant chemotherapy regimen can offer an improved event-free survival compared with neoadjuvant chemotherapy alone and has the potential for achieving a pathologic response [pCR, the disappearance of cancer] in one in four patients.”

Among patients treated with Opdivo, the risk of disease recurrence, progression or death was reduced by 42% with a median follow-up of 25.4 months, according to the news release, which also stated that 70% of patients in the Opdivo arm experienced 18-month event-free survival, compared to 50% of patients in the chemotherapy and placebo groups. Additionally, 25% of the patients in the Opdivo group reached pCR, compared to 4.7% of patients in the chemotherapy and placebo group in the intent-to-treat population.

According to Bristol Myers Squibb, Opdivo is associated with warnings and precautions for severe and fatal immune-mediated side effects including pneumonitis (inflammation of the lung tissue), colitis (inflammation of the colon), hepatitis and hepatotoxicity (liver toxicity), endocrinopathies (endocrine gland disease), dermatologic adverse reactions, nephritis (kidney inflammation) and renal dysfunction as well as infusion-related reactions complications of allogeneic hematopoietic stem cell transplantation (HSCT) and embryo-fetal toxicity.

Side effects were similar to other clinical trials of Opdivo and chemotherapy, with 5.3% of patients treated with Opdivo unable to undergo surgery due to side effects compared to 3.5% of the placebo arm. The agency reported that 4.5% of those who received presurgical Opdivo and surgery had surgical delays due to side effects, compared to 3.9% of the placebo arm.

According to the FDA, the recommended dosage of Opdivo is 360 milligrams every three weeks before surgery and 480 milligrams every four weeks after surgery, and it should be administered prior to chemotherapy when given on the same day.

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