Longer term ( 18 month ) survival data from CheckMate -057, an open-label, randomized phase 3 study evaluating Nivolumab [ Opdivo ] ( n=292 ) versus Docetaxel [ Taxotere ] ( n=290 ) in previously treated patients with advanced, non-squamous ( NSQ ) non-small cell lung cancer ( NSCLC ), were presented at the European Cancer Congress ( ECC 2015 ) and published in the New England Journal of Medicine ( NEJM ).
Nivolumab continued to demonstrate superior overall survival ( OS ) [ the study’s primary endpoint ] with an estimated 39% of patients alive at 18 months ( 95% CI, 34-45 ) versus 23% for Docetaxel, based on a minimum follow-up of 17.1 months.
Nivolumab also continued to demonstrate a reduction in the risk of death by 28% ( a hazard ratio of 0.72; 95% CI, 0.60 - 0.88 ).
In the study, grade 3-4 treatment-related adverse events were reported in 10% of patients treated with Nivolumab versus 54% in the Docetaxel arm.
CheckMate -057 is a phase 3, open-label, randomized clinical trial that evaluated patients with advanced NSQ NSCLC who had progressed during or after one prior Platinum doublet-based chemotherapy regimen. The trial included patients regardless of their PD-L1 status. Secondary endpoints included objective response rate ( ORR ) and progression-free survival ( PFS ).
Patients enrolled in the trial received Nivolumab 3 mg/kg every two weeks versus standard of care, Docetaxel, at 75 mg/m2 every three weeks.
In the trial, Nivolumab demonstrated continued superior overall survival benefit, with an estimated 51% of patients alive at one year versus 39% for Docetaxel, and an estimated 39% of patients alive at 18 months ( 95% CI, 34-45 ) versus 23% for Docetaxel, based on a minimum follow-up of 17.1 months.
CheckMate -057 also evaluated the efficacy of Nivolumab by tumor PD-L1 expression. Of randomized patients, 78% ( 455/582 ) had tumor samples evaluable for PD-L1 expression. Rates of PD-L1 expressing tumors were balanced between groups.
PD-L1 status was predictive for benefit from Nivolumab, across pre-specified 1%, 5%, and 10% expression levels.
In PD-L1 non-expressors, overall survival was similar between Nivolumab and Docetaxel, with improved durability of responses seen in patients treated with Nivolumab versus Docetaxel.
In addition, clinical results showed confirmed ORR was significantly higher for Nivolumab ( 19% ) than Docetaxel ( 12% ).
For patients administered Nivolumab, median duration of response was 17.2 months and 5.6 months for Docetaxel.
One-year progression-free survival was 19% for Nivolumab ( 95% CI, 14-23 ) and 8% for Docetaxel ( 95% CI, 5-12 ). Median PFS was 2.3 months for Nivolumab ( 95% CI, 2.2-3.3 ) and 4.2 months for Docetaxel ( 95% CI, 3.5-4.9 ).
The safety profile of Nivolumab in CheckMate -057 was consistent with prior studies and similar across expressors and non-expressors.
Treatment-related adverse events were low in severity with Nivolumab and occurred less frequently ( any grade: 69%; grade 3-4: 10% ) than Docetaxel ( any grade: 88%; grade 3-4: 54% ), including both hematologic and non-hematologic toxicities.
Treatment-related serious adverse events were reported less frequently with Nivolumab ( any grade: 7%; grade 3-4: 5% ) than Docetaxel ( any grade: 20%; grade 3-4: 18% ).
Discontinuation due to treatment–related adverse events was less frequent with Nivolumab ( 5% ) than Docetaxel ( 15% ).
Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organization ( WHO ).
Lung cancer results in more deaths worldwide than colorectal, breast and prostate cancers combined.
Non-small cell lung cancer is one of the most common types of the disease and accounts for approximately 85% of cases.
Nivolumab is a programmed death-1 ( PD-1 ) immune checkpoint inhibitor. ( Xagena )
Source: BMS, 2015