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MSD announced 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 (programmed death receptor-ligand 1) expression in patients with previously treated advanced non-small cell lung cancer (NSCLC). In the Phase II/III study, KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 (programmed death receptor-1) therapy, significantly improved overall survival (OS) compared to chemotherapy in patients with any level of PD-L1 expression, as defined by a tumour proportion score (TPS) of 1% or more. The results were published in The Lancet and will be presented at the European Society for Medical Oncology (ESMO) Asia 2015 Congress.
“Because lung cancer remains one of the most common and most challenging cancers to treat, understanding the role that pembrolizumab can play in helping patients was essential to our development program. In this study in patients with PD-L1 expression of 1% or greater, pembrolizumab demonstrably improved overall survival compared to chemotherapy in previously-treated patients with non-small cell lung cancer, including both squamous and non-squamous histologies,” said Dr Roger M Perlmutter, president,Merck & Co., Inc.’s/MSDResearch Laboratories.
Overall Survival Findings from KEYNOTE-010
The Phase II/III KEYNOTE-010 study included 1034 patients with advanced NSCLC with PD-L1 expression (TPS of 1% or more). Similar findings were shown in patients who received of pembrolizumab at doses of 2mg/kg every three weeks (n=345) and 10mg/kg every three weeks (n=346). Both groups of patients who received pembrolizumab were compared to patients who received docetaxel (n=343). PD-L1 expression was assessed by the immunohistochemistry companion diagnostic test PD-L1 IHC 22C3 PharmDx, made by Dako North America, Inc., an Agilent Technologies Company. 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).1
In the total study population (all levels of PD-L1 expression), both doses of pembrolizumab studied significantly improved overall survival (OS) compared with docetaxel. Specifically, pembrolizumab resulted in a 29% improvement in OS for the 2mg/kg dose (HR 0.71, P=0.0008; 95% CI, 0.58–0.88) and a 39% improvement in OS for the 10mg/kg dose (HR 0.61, P<0.0001; 95% CI, 0.49–0.75), compared to docetaxel. The estimated 1-year OS rates for pembrolizumab were 43.2% and 52.3%, respectively, compared to 34.6% for docetaxel. Median OS for pembrolizumab were 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).1
Among patients with higher levels of PD-L1 expression (a TPS score of 50% or greater), OS was superior for both pembrolizumab doses compared with docetaxel. Specifically, pembrolizumab improved OS by 46 percent for the 2mg/kg dose (HR 0.54, P=0.0002; 95% CI, 0.38–0.77) and by 50% for the 10mg/kg dose (HR 0.50, P<0.0001; 95% CI, 0.36–0.70), compared to docetaxel. Median OS for pembrolizumab (2mg/kg and 10mg/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).1
Additional Findings from KEYNOTE-010
In the total study population, pembrolizumab prolonged progression-free survival (PFS) at both doses, though statistical significance was not met (HR 0.88 [95% CI, 0.74–1.05], P=0.07 for 2mg/kg; HR 0.79 [95% CI, 0.66–0.94], P=0.004 for 10mg/kg). Among patients treated with pembrolizumab (2mg/kg and 10mg/kg, respectively), median PFS 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).1
Patients with higher levels of PD-L1 expression (a TPS score of 50% or greater) who were treated with pembrolizumab had significantly prolonged PFS compared to docetaxel (HR 0.59 [95% CI, 0.44–0.78, P=0.0001] for 2mg/kg; HR 0.59 [95% CI, 0.45–0.78, P<0.0001] for 10mg/kg). Among patients treated with pembrolizumab (2mg/kg and 10mg/kg, respectively), median PFS 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).1
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 (2mg/kg and 10mg/kg, respectively) included: decreased appetite (n=3, n=1), fatigue (n=4, n=6), nausea (n=1, n=2), rash (n=1, n=1), diarrhoea (n=2, n=0), asthenia (n=1, n=2), stomatitis (n=0, n=1), and anaemia (n=3, n=1). The most common immune-mediated adverse events for pembrolizumab (2mg/kg and 10mg/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 2mg/kg dose (pneumonitis [n=2], pneumonia [n=1]) and three treatment-related deaths among patients receiving pembrolizumab at the 10mg/kg dose (myocardial infarction [n=1], pneumonia [n=1], and pneumonitis [n=1]).1