ESMO 2016: Pembrolizumab a New Option for First-Line Treatment of Patients With Advanced Lung Cancer and High PD-L1 Expression
Pembrolizumab (Keytruda) is set to become a new option for first-line treatment of patients with advanced lung cancer and high programmed cell death ligand 1 (PD-L1) expression, according to the results of the phase III KEYNOTE-024 trial presented by Reck et al at the 2016 European Society for Medical Oncology (ESMO) Congress in Copenhagen (Abstract LBA8_PR) and published by Reck et al in The New England Journal of Medicine.
“Pembrolizumab is a PD-1 [programmed cell death protein 1] antibody approved for second-line treatment of patients with advanced non–small-cell lung cancer (NSCLC) and PD-L1 expression in their tumor cells,” said lead author Martin Reck, MD, PhD, Chief Oncology Physician, Department of Thoracic Oncology at the Lung Clinic Grosshansdorf, Germany. “KEYNOTE-024 is the first phase III trial of pembrolizumab as first-line treatment in patients with high PD-L1 expression, who represent 27% to 30% of those with advanced NSCLC.”
KEYNOTE-024
KEYNOTE-024 investigated the efficacy of pembrolizumab compared to standard of care with platinum-based chemotherapy in untreated patients with advanced NSCLC and high PD-L1 expression (defined as expression in at least 50% of tumor cells). Patients with EGFR-activating mutations and ALK translocations were excluded from recruitment. “There is a substantial need to find better options than chemotherapy for these patients,” said Dr. Reck.
The trial included 305 patients from 16 countries who were randomized 1:1 to pembrolizumab or chemotherapy. Patients in the chemotherapy arm who had disease progression were eligible to crossover to pembrolizumab as second-line treatment—this occurred in 44% of these patients.
Study Findings
The investigators found that pembrolizumab significantly improved the primary endpoint of progression-free survival by approximately 4 months compared to chemotherapy (10.3 vs 6.0 months, hazard ratio [HR] = 0.50). The secondary endpoint of overall survival was also significantly prolonged, and 80% of patients on pembrolizumab were alive at 6 months compared to 72% on chemotherapy (HR = 0.60).
“The significant improvement in overall survival with pembrolizumab was remarkable, given that more than 40% of patients crossed over from the control arm to pembrolizumab after progression of the disease,” said Dr. Reck.
Pembrolizumab treatment was associated with a higher overall response rate compared to chemotherapy (45% vs 28%), a longer duration of response, and lower incidences of all and serious (grade 3/4) adverse events.
“These data will completely change the management of patients with advanced NSCLC,” said Dr. Reck. “All endpoints of efficacy and tolerability favored treatment with pembrolizumab, suggesting it should become a standard of care for first-line treatment of patients with advanced NSCLC and high PD-L1 expression. This is primarily an opportunity for patients without oncogenic alterations. More information is needed for those with alterations.”
He concluded,“This is a landmark trial for the 30% of patients with advanced NSCLC who are high expressers of PD-L1. The new treatment algorithm should include upfront testing for PD-L1 expression to identify patients who will benefit from first-line treatment with pembrolizumab.”
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