The US Food and Drug Administration (FDA) has approved Bristol-Myers Squibb Company's Opdivo (nivolumab) injection, for intravenous use, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

Patients with EGFR mutation or ALK translocation should have disease progression on appropriate targeted therapy prior to receiving Opdivo. In a phase 3 trial, CheckMate -057, Opdivo demonstrated superior overall survival (OS) in previously treated metastatic non-squamous NSCLC compared to chemotherapy, with a 27 per cent reduction in the risk of death (hazard ratio: 0.73 [95 per cent CI: 0.60, 0.89; p=0.0015]), based on a prespecified interim analysis. The median OS was 12.2 months in the Opdivo arm (95 per cent CI: 9.7, 15.0) and 9.4 months in the docetaxel arm (95 per cent CI: 8.0, 10.7). This approval expands Opdivo’s indication for previously treated metastatic squamous NSCLC to include the non-squamous patient population. Squamous and non-squamous NSCLC together represent approximately 85 per cent to 90 per cent of lung cancer cases.

Opdivo is associated with immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, encephalitis, other adverse reactions; infusion reactions; and embryofetal toxicity.

“Improving survival for cancer patients represents the ultimate goal of treatment,” said Murdo Gordon, senior vice president and head of worldwide markets, Bristol-Myers Squibb.

“With today’s FDA approval, it is encouraging to know that Opdivo will be available to significantly more patients with metastatic NSCLC, helping to improve treatment outcomes for patients who have been previously treated. We hope that our efforts to bring innovative Immuno-Oncology treatments forward for patients will help increase survivorship and positively impact the lung cancer community.”

This approval is the third for Opdivo in the United States this year, and is based on the results of the CheckMate -057 trial, a phase 3 trial which demonstrated superior OS benefit for Opdivo vs. docetaxel in previously treated metastatic NSCLC. Opdivo is the only PD-1 therapy to have been studied in a phase 3 trial of patients with previously treated squamous NSCLC and a separate phase 3 trial of patients with previously treated non-squamous NSCLC. Biomarker testing is not required for Opdivo.

“Non-small cell lung cancer is a difficult to treat disease with high mortality, and patients with squamous and non-squamous NSCLC often respond differently to treatment,” said Dr. Roy Herbst, chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven.

“Opdivo is becoming an important treatment option for more patients with previously treated metastatic NSCLC, and is a welcome addition to our therapy of this disease.”

CheckMate -057 is a landmark, comparative study designed with the goal of demonstrating survival. Clinical results from CheckMate -057 were recently presented at the 2015 European Cancer Congress with simultaneous publication in the New England Journal of Medicine. CheckMate -057 is a phase 3, open-label, randomized clinical trial that evaluated Opdivo (3 mg/kg administered intravenously every two weeks) (n=292) vs. docetaxel (75 mg/m2 administered intravenously every three weeks) (n=290), in patients with metastatic non-squamous NSCLC who had experienced disease progression during or after one prior platinum doublet-based chemotherapy regimen. Appropriate targeted therapy may have been given to patients with known EGFR mutation or ALK translocation. This study included patients regardless of their PD-L1 (programmed death ligand-1) expression status. The primary endpoint of this trial was OS.

The median OS was 12.2 months in the Opdivo arm (95 per cent CI: 9.7, 15.0) and 9.4 months in the docetaxel arm (95 per cent CI: 8.0, 10.7). The hazard ratio (HR) was 0.73 (95 per cent CI: 0.60, 0.89; p=0.0015), which translates to a 27 per cent reduction in the risk of death with Opdivo compared to docetaxel. The prespecified interim analysis was conducted when 413 events were observed (93 per cent of the planned number of events for final analysis). Additional secondary endpoints include investigator-assessed objective response rate (ORR) and progression-free survival (PFS). The ORR in the Opdivo arm was 19 per cent (56/292; 4 complete responses, 52 partial responses) (95 per cent CI: 15, 24) and 12 per cent with docetaxel (36/290; 1 complete response, 35 partial responses) (95 per cent CI: 9, 17) p=0.02. The median duration of response was 17 months in the Opdivo arm and 6 months in the docetaxel arm. Median PFS was 2.3 months in the Opdivo arm vs. 4.2 months with docetaxel; HR=0.92 (95 per cent CI:0.77, 1.11, p=0.39).

“With today’s announcement, Opdivo represents the only PD-1 inhibitor approved for patients regardless of PD-L1 expression, and offers significant improvement over the current standard chemotherapy,” said Michael Giordano, senior vice president, head of development, oncology, Bristol-Myers Squibb.

“Through our leadership in immuno-oncology research, we have taken a comprehensive approach to better understanding and treating metastatic NSCLC, with a primary focus on patients who are in need of new options. We are committed to building upon the promise that Opdivo has demonstrated for patients and providing a potential survival benefit in devastating diseases, like metastatic NSCLC.”

The safety profile of Opdivo in CheckMate -057 was consistent with prior studies. Serious adverse reactions occurred in 47 per cent of patients receiving Opdivo. The most frequent serious adverse reactions in at least 2 per cent of patients receiving Opdivo were pneumonia, pulmonary embolism, dyspnea, pleural effusions and respiratory failure. Opdivo was discontinued in 13 per cent of patients and was delayed in 29 per cent of patients for an adverse reaction. The most common adverse reactions (reported in =20per cent of patients) were fatigue (49 per cent), musculoskeletal pain (36per cent), cough (30 per cent), decreased appetite (29 per cent) and constipation (23 per cent).

“The approval of Opdivo for patients with previously treated metastatic NSCLC represents a major advancement in the way we are able to address the unmet needs of these patients, especially for those who have progressed on prior treatment and, until now, may have had limited options,” said Andrea Ferris, president and chairman of LUNGevity Foundation.

“Bristol-Myers Squibb has shown unwavering commitment to improving survival expectations for patients with metastatic NSCLC and I applaud their work, along with the FDA, in making this treatment option available to more patients.”

Bristol-Myers Squibb has partnered with Dako, an Agilent Technologies company, to develop PD-L1 IHC 28-8 PharmDx, a test which was used to assess PD-L1 expression in the CheckMate -057 trial. This test is now approved by the FDA as a complementary diagnostic, which will provide additional information for physicians. These tests are distinct from companion diagnostics, which are essential for safe and effective use of a drug. Biomarker testing is not required for Opdivo.

Lung cancer is one of the leading causes of cancer deaths in the United States. NSCLC is one of the most common types of the disease and accounts for approximately 85 per cent to 90 per cent of lung cancer cases. Squamous NSCLC accounts for approximately 25 per cent to 30 per cent of all lung cancer cases, while non-squamous NSCLC accounts for approximately 45 per cent to 60 per cent of all lung cancer cases. Survival rates vary depending on the stage and type of the cancer and when it is diagnosed. For Stage IV NSCLC, the five-year survival rate is one per cent.