Oncology Xagena
Two-year overall survival data from two pivotal phase 3 studies evaluating Nivolumab ( Opdivo ) versus Docetaxel in previously treated metastatic non-small cell lung cancer ( NSCLC ) were announced.
Nivolumab has continued to demonstrate improved overall survival ( OS ), the primary endpoint for both studies, at the landmark two-year time point.
In CheckMate -057, a trial in previously treated non-squamous NSCLC, 29% of patients treated with Nivolumab were alive at two years ( n=81/292 ) versus 16% of those treated with Docetaxel ( n=45/290 ) ( hazard ratio, HR=0.75 [ 95% CI: 0.63, 0.91 ] ).
In CheckMate -017, a trial in previously treated squamous NSCLC, 23% of patients treated with Nivolumab were alive at two years ( n=29/135 ) versus 8% of those treated with Docetaxel ( n=11/137 ) ( HR=0.62 [ 95% CI: 0.47, 0.80 ] ).
In Checkmate -057 and -017, treatment-related adverse events occurred in 71% and 61% of Nivolumab-treated patients. The safety profile of Opdivo at two years was consistent with previous reports of data from both studies.
CheckMate -057
CheckMate -057 is a phase 3, open-label, randomized clinical trial that evaluated patients with advanced non-squamous non-small cell lung cancer who had progressed during or after one prior Platinum doublet-based chemotherapy regimen.
The trial included patients regardless of their PD-L1 status.
The study’s primary endpoint was overall survival and secondary endpoints included objective response rate ( ORR ), progression-free survival ( PFS ) and efficacy by tumor PD-L1 expression.
Patients enrolled in the trial were administered Nivolumab 3 mg/kg every two weeks versus standard of care, Docetaxel, at 75 mg/m2 every three weeks.
At two years, 29% of patients treated with Nivolumab were alive ( n=81/292 ) versus 16% of those treated with Docetaxel ( n=45/290 ) ( HR=0.75 [ 95% CI: 0.63, 0.91 ).
Median overall survival was 12.2 months with Nivolumab ( 95% CI: 9.7, 15.1 ) versus 9.5 months with Docetaxel ( 95% CI: 8.1, 10.7 ).
CheckMate -057 also evaluated the efficacy of Nivolumab by tumor PD-L1 expression. Of randomized patients, 78% ( 455/582 ) had tumor samples allowing the assessment of PD-L1 expression. Rates of PD-L1 expressing tumors were balanced between groups.
Across pre-specified expression levels ( 1%, 5%, and 10% ), PD-L1 status was associated with enhanced magnitude of benefit from Nivolumab.
In patients who did not express PD-L1, overall survival was similar between Nivolumab and Docetaxel.
CheckMate -017
CheckMate -017 was a phase 3, open-label, randomized clinical trial that evaluated Nivolumab 3 mg/kg every two weeks versus standard of care, Docetaxel 75 mg/m2 every three weeks, in patients with advanced squamous NSCLC who had progressed during or after one prior Platinum doublet-based chemotherapy regimen.
The primary endpoint was overall survival and secondary endpoints included progression-free survival and response rate. The trial included patients regardless of their PD-L1 expression status.
In CheckMate -017, 23% of patients treated with Opdivo were alive at two years ( n=29/135 ) versus 8% of those treated with Docetaxel ( n=11/137 ) ( HR=0.62 [ 95% CI: 0.47, 0.80 ] ).
Median overall survival was 9.2 months with Nivolumab ( 95% CI: 7.3, 12.6 ) versus 6.0 months with Docetaxel ( 95% CI: 5.1, 7.3 ).
The safety profile of Nivolumab remained consistent with previous reports of data from both CheckMate -057 and CheckMate -017 trials, and treatment-related adverse events of any grade and grade 3/4 were less frequent with Nivolumab versus Docetaxel. The frequencies of the most common treatment-related adverse effects across the two trials remained lower with Nivolumab than with Docetaxel.
In CheckMate -057, the most common treatment-related adverse effects for Nivolumab and Docetaxel included fatigue ( 17%, 29%, respectively ), nausea ( 12%, 26%, respectively ), decreased appetite ( 11%, 16%, respectively ), and asthenia ( 10%, 18%, respectively ).
In CheckMate -017, the most common treatment-related adverse effects for Nivolumab and Docetaxel included fatigue ( 16%, 33%, respectively ), decreased appetite ( 11%, 19%, respectively ), asthenia ( 11%, 14%, respectively ) and nausea ( 9%, 23%, respectively ). ( Xagena )
Source: BMS, 2016
XagenaMedicine_2016
