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Immuno-oncology therapy: Opdivo for the treatment of patients with previously treated metastatic squamous non-small cell Lung cancer, approved by FDA


The FDA ( Food and Drug Administration ) has approved Opdivo ( Nivolumab ) injection, for intravenous use, for the treatment of patients with metastatic squamous non-small cell lung cancer ( NSCLC ) with progression on or after Platinum-based chemotherapy.
Opdivo is the first and only PD-1 ( programmed death receptor-1 ) therapy to demonstrate overall survival in previously treated metastatic squamous NSCLC.
Opdivo demonstrated significantly superior overall survival ( OS ) versus Docetaxel ( Taxotere ), with a 41% reduction in the risk of death ( hazard ratio, HR=0.59 [ 95% CI: 0.44, 0.79; p=0.00025 ] ), in a prespecified interim analysis of a phase III clinical trial.
The median overall survival was 9.2 months in the Opdivo arm ( 95% CI: 7.3, 13.3 ) and 6 months in the Docetaxel arm ( 95% CI: 5.1, 7.3 ).

This approval is the second for Opdivo in the United States within three months, and is based on the results of CheckMate -017 and CheckMate -063.

Opdivo is associated with immune-mediated pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, hypothyroidism and hyperthyroidism, other adverse reactions; and embryofetal toxicity.

Superior survival versus standard of care

CheckMate -017 was a landmark phase III, open-label, randomized, multinational, multicenter clinical trial that evaluated Opdivo ( 3 mg/kg intravenously over 60 minutes every two weeks ) ( n=135 ) vs. standard of care, Docetaxel ( 75 mg/m2 intravenously administered every 3 weeks ) ( n=137 ), in patients with metastatic squamous NSCLC who had progressed during or after prior Platinum doublet-based chemotherapy regimen.
This trial included patients regardless of their PD-L1 status. The primary endpoint of this trial was overall survival.
In January, the trial was stopped based on an assessment conducted by the independent Data Monitoring Committee ( DMC ), which concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo compared to Docetaxel.
The prespecified interim analysis was conducted when 199 events ( 86% of the planned number of events for final analysis ) were observed ( 86 in the Opdivo arm and 113 in the Docetaxel arm ).
Opdivo is the only FDA-approved monotherapy to demonstrate proven superior overall survival compared to standard of care in more than 15 years in previously treated metastatic squamous NSCLC.
The median overall survival was 9.2 months in the Opdivo arm ( 95% CI: 7.3, 13.3 ) and 6 months in the Docetaxel arm ( 95% CI: 5.1, 7.3 ).
The hazard ratio was 0.59 ( 95% CI: 0.44, 0.79; p=0.00025 ). This hazard ratio translates to a 41% reduction in the risk of death with Opdivo compared to Docetaxel.

The FDA approval of Opdivo introduces an entirely new treatment modality that has demonstrated unprecedented results for the treatment of previously treated metastatic squamous NSCLC, with the potential to replace chemotherapy for these patients.

Safety profile

The safety profile of Opdivo in squamous NSCLC was established in CheckMate -063, a phase II single-arm, open-label, multinational, multicenter trial of Opdivo, administered as a single agent in patients with metastatic squamous NSCLC who have progressed after receiving a Platinum-based therapy and at least one additional systemic treatment regimen ( n=117 ).
Patients received 3 mg/kg of Opdivo administered intravenously over 60 minutes every 2 weeks.
This trial included patients regardless of their PD-L1 status.
The most common adverse reactions ( reported in greater than or equal to 20% of patients ) were fatigue ( 50% ), dyspnea ( 38% ), musculoskeletal pain ( 36% ), decreased appetite ( 35% ), cough ( 32% ), nausea ( 29% ), and constipation ( 24% ).
Serious adverse reactions occurred in 59% of patients receiving Opdivo.
The most frequent serious adverse reactions reported in greater than or equal to 2% of patients were dyspnea, pneumonia, chronic obstructive pulmonary disease exacerbation, pneumonitis, hypercalcemia, pleural effusion, hemoptysis, and pain.
Opdivo was discontinued due to adverse reactions in 27% of patients.
Twenty-nine percent of patients receiving Opdivo had a drug delay for an adverse reaction.
With at least 10 months of minimum follow up for all patients, the confirmed objective response rate ( ORR ), the study’s primary endpoint, was 15% ( 17/117 ) ( 95% CI = 9, 22 ) of which all were partial responses.
The median time to onset of response was 3.3 months ( range: 1.7 to 8.8 months ) after the start of Opdivo treatment.
Seventy-six percent of Opdivo responders ( 13/17 patients ) had ongoing responses with durability of response ranging from 1.9+ to 11.5+ months; 10 of these 17 ( 59% ) patients had durable responses of 6 months or longer.

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% of cases.
Squamous cell NSCLC accounts for approximately 25 to 30% of all lung cancers.
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 1%. ( Xagena )

Source: BMS, 2015

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