Oncology Xagena
Results from the pivotal KEYNOTE-010 study, the first study of its kind to evaluate the potential of an immunotherapy compared to chemotherapy based on prospective measurement of PD-L1 expression in patients with advanced non-small cell lung cancer ( NSCLC ) were presented at the European Society for Medical Oncology ( ESMO ) Asia 2015 Congress.
In the Phase 2/3 study, Keytruda ( Pembrolizumab ), an anti-PD-1 ( programmed death receptor-1 ) therapy, significantly improved overall survival compared to chemotherapy in patients with any level of PD-L1 expression, as defined by a tumor proportion score ( TPS ) of 1% or more.
The results were published in The Lancet.
The phase 2/3 KEYNOTE-010 study included 1,034 patients with advanced NSCLC with PD-L1 expression ( TPS of 1% or more ). Similar findings were shown in patients who received the FDA-approved dose of Pembrolizumab ( 2 mg/kg every three weeks ) ( n=345 ) and an investigational dose of Pembrolizumab ( 10 mg/kg every three weeks ) ( n=346 ).
Both groups of patients who received Pembrolizumab were compared to patients who received Docetaxel [ Taxotere ] ( n=343 ).
PD-L1 expression was assessed by the immunohistochemistry companion diagnostic test PD-L1 IHC 22C3 PharmDx, made by Dako North America.
The findings from KEYNOTE-010 are based on the final study analysis.
The median follow-up was 13.1 months ( IQR, 8.6-17.7 ).
In the total study population ( all levels of PD-L1 expression ), both doses of Pembrolizumab studied significantly improved overall survival compared with Docetaxel.
Specifically, Pembrolizumab resulted in a 29% improvement in overall survival ( OS ) for the 2 mg/kg dose ( hazard ratio, HR=0.71, P=0.0008; 95% CI, 0.58-0.88 ) and a 39% improvement in overall survival for the 10 mg/kg dose ( HR=0.61, P less than 0.0001; 95% CI, 0.49-0.75 ), compared to Docetaxel.
The estimated 1-year overall survival rates for Pembrolizumab were 43.2% and 52.3%, respectively, compared to 34.6% for Docetaxel.
Median overall survival for Pembrolizumab was 10.4 months ( 95% CI, 9.4-11.9 ) and 12.7 months ( 95% CI, 10.0-17.3 ), respectively, compared to 8.5 months for Docetaxel ( 95% CI, 7.5-9.8 ).
Among patients with higher levels of PD-L1 expression ( a TPS score of 50% or greater ), overall survival was superior for both Pembrolizumab doses compared with Docetaxel.
Specifically, Pembrolizumab improved overall survival by 46% for the 2 mg/kg dose ( HR=0.54, P=0.0002; 95% CI, 0.38-0.77 ) and by 50% for the 10 mg/kg dose ( HR=0.50, P less than 0.0001; 95% CI, 0.36-0.70 ), compared to Docetaxel.
Median overall survival for Pembrolizumab ( 2 mg/kg and 10 mg/kg, respectively ) was 14.9 months ( 95% CI, 10.4 to not reached ) and 17.3 months ( 95% CI, 11.8 to not reached ), compared to 8.2 months for Docetaxel ( 95% CI, 6.4-10.7 ).
In the total study population, Pembrolizumab prolonged progression-free ( PFS ) survival at both doses, though statistical significance was not met ( HR=0.88 [ 95% CI, 0.74-1.05 ], P=0.07 for 2 mg/kg; HR=0.79 [ 95% CI, 0.66-0.94 ], P=0.004 for 10 mg/kg ).
Among patients treated with Pembrolizumab ( 2 mg/kg and 10 mg/kg, respectively ), median progression-free survival was 3.9 months ( 95% CI, 3.1-4.1 ) and 4.0 months ( 95% CI, 2.7-4.3 ), compared to 4.0 months for Docetaxel ( 95% CI, 3.1-4.2 ).
Patients with higher levels of PD-L1 expression ( a TPS score of 50% or greater ) who were treated with Pembrolizumab had significantly prolonged progression-free survival compared to Docetaxel ( HR=0.59 [ 95% CI, 0.44-0.78, P=0.0001 ] for 2 mg/kg; HR=0.59 [ 95% CI, 0.45-0.78, P less than 0.0001 ] for 10 mg/kg ).
Among patients treated with Pembrolizumab ( 2 mg/kg and 10 mg/kg, respectively ), median progression-free survival was 5.0 months ( 95% CI, 4.0-6.5 ) and 5.2 months ( 95% CI, 4.1-8.1 ), compared to 4.1 months for Docetaxel ( 95% CI, 3.6-4.3 ).
Additionally, the safety of Pembrolizumab was consistent with what has been seen in previous trials among advanced lung cancer patients.
Grade 3-5 treatment-related adverse events for Pembrolizumab ( 2 mg/kg and 10 mg/kg, respectively ) included: decreased appetite ( n=3, n=1 ), fatigue ( n=4, n=6 ), nausea ( n=1, n=2 ), rash ( n=1, n=1 ), diarrhea ( n=2, n=0 ), asthenia ( n=1, n=2 ), stomatitis ( n=0, n=1 ), and anemia ( n=3, n=1 ).
The most common immune-mediated adverse events for Pembrolizumab ( 2 mg/kg and 10 mg/kg, respectively ) included: hypothyroidism ( 8% [ n=28 ], 8% [ n=28 ] ), hyperthyroidism ( 4% [ n=12 ], 6% [ n=20 ] ), and pneumonitis ( 5% [ n=16 ], 4% [ n=15 ] ).
There were three treatment-related deaths among patients receiving Pembrolizumab at the 2 mg/kg dose ( pneumonitis [ n=2 ], pneumonia [ n=1 ] ) and three treatment-related deaths among patients receiving Pembrolizumab at the 10 mg/kg dose ( myocardial infarction [ n=1 ], pneumonia [ n=1 ], and pneumonitis [ n=1 ] ). ( Xagena )
Source: Merck & Co, 2015
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