The U.S. Food and Drug Administration has approved the use of Opdivo (nivolumab) for the treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC) that has progressed during or after platinum-based chemotherapy. Opdivo, made by Bristol-Myers Squibb, works by inhibiting the PD-1 pathway, which blocks the body's immune system from attacking cancer cells.
Opdivo is being approved for this indication after recently receiving priority review designation and breakthrough therapy status-with approval coming three months ahead of the prescription drug fee goal date of January 2 (OT 10/10/15 issue).
Opdivo was also approved earlier this year for the treatment of patients with metastatic squamous NSCLC that has progressed on or after platinum-based chemotherapy (OT 4/10/15 issue).
"There is still a lot to learn about the PD-1/PD-L1 pathway and its effects in lung cancer, as well as other tumor types," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release. "While Opdivo 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."
Opdivo has also previously received accelerated approval to treat patients with unresectable or metastatic melanoma who no longer respond to other drugs (OT 1/25/15 issue); and it previously received Breakthrough Therapy status for the treatment of patients with metastatic renal cell carcinoma (OT 10/10/15 issue). Opdivo was also recently approved for use in combination with Yervoy (ipilimumab) for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma, which was the first approval of a combination regimen of two immuno-oncology agents for the treatment of cancer.
Safety and Effectiveness
Opdivo's approval for this new indication was based on data from the international, open-label CheckMate-057 trial of 582 patients with advanced NSCLC that had progressed during or after treatment with platinum-based chemotherapy and appropriate biologic therapy. Patients were included regardless of their PD-L1 status, and were randomized to receive Opdivo or docetaxel.
Median overall survival for patients who received Opdivo was 12.2 months compared with 9.4 months for patients who received docetaxel. Of the patients who received Opdivo, 19 percent had their tumors completely or partially shrink (for 17 months on average), compared with 12 percent of patients who received docetaxel (partial shrinkage for an average of six months).
The safety profile for Opdivo for patients in the CheckMate-057 trial was consistent with prior studies: The most frequent serious adverse reactions (occurring in at least two percent of patients) were pneumonia, pulmonary embolism, dyspnea, pleural effusions, and respiratory failure. The most common adverse reactions were fatigue, musculoskeletal pain, cough, decreased appetite, and constipation.
PD-L1 Biomarker Test Also Approved
While patients who received Opdivo lived longer than those who received docetaxel across the study, an evaluation of samples from a subgroup of patients' tumors suggests that the level of PD-L1 expression in NSCLC tumors 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.
Biomarker testing, though, is not required for treatment with Opdivo.
The test is marketed by Dako, an Agilent Technologies Company.
Clinical Quick Facts: Opdivo
Drug: Opdivo (nivolumab)
Approved Indication: Treatment of patients with metastatic non-squamous non-small cell lung cancer that has progressed during or after platinum-based chemotherapy
Serious Side Effects: Pneumonia, pulmonary embolism, dyspnea, pleural effusions, and respiratory failure
Common Side Effects: Fatigue, musculoskeletal pain, cough, decreased appetite, and constipation