COPENHAGEN – Chalk up another one for immunotherapy: the PD-1 checkpoint inhibitor pembrolizumab cut the risk of disease progression or death in half among select patients with non–small cell lung cancer (NSCLC), compared with standard platinum doublet chemotherapy, in the first-line setting.
Among 305 patients with non–small cell lung cancers with 50% or greater expression of the programmed death ligand 1 (PD-L1), median progression-free survival (PFS) for patients treated with pembrolizumab (Keytruda) was 10.3 months, compared with 6 months for patients assigned to receive platinum-based chemotherapy at the investigators discretion (hazard ratio, 0.50, P less than .001), reported Martin Reck, MD, from the department of thoracic oncology at the Lung Clinic Grosshansdorf, in Germany.
Dr. Martin Reck
Results of the KEYNOTE-024 study were also published online in the New England Journal of Medicine (2016 Oct 9. doi: 10.1056/NEJMoa1606774). Approximately 23%-30% of patients with advanced non–small cell lung cancers have tumors that express PD-L1 on the membrane of at least 50% of tumor cells, making them attractive targets for pembrolizumab, which is a monoclonal antibody directed against programmed death 1 (PD-1). Pembrolizumab disengages the brake on the immune system caused by the interaction of receptor PD-1 with the PD-L1 and PD-L2 ligands.
The study was conducted to compare upfront pembrolizumab with platinum-based chemotherapy in patients with newly diagnosed advanced NSCLC that did not carry targetable EGFR-activating mutations or ALK translocations.
A total of 305 patients from 16 countries with untreated stage IV NSCLC, good performance status, and tumors with a 50% or greater expression of PD-L1 were enrolled and randomized to either pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Or four to six cycles of platinum-doublet chemotherapy at the investigator’s discretion. The combinations included carboplatin plus pemetrexed, cisplatin plus pemetrexed, carboplatin plus gemcitabine, cisplatin plus gemcitabine, or carboplatin plus paclitaxel.
At a median follow-up of 11.2 months, 48.1% of patients assigned to pembrolizumab were still on treatment, as were 10% of those assigned to standard chemotherapy.
As noted before, PFS, the primary endpoint, was significantly better with pembrolizumab, as was the secondary endpoint of overall survival at 6 months. In all, 80% of patients treated with pembrolizumab were still alive at 6 months, compared with 72% of patients on chemotherapy (HR, 0.60; P = .005).
The confirmed response rate was also higher in the pembrolizumab arm, at 44.8% vs. 27.8%(P = .0011), and the median duration of response was longer (not reached vs. 6.3 months). There were six complete responses in the pembrolizumab arm.
Pembrolizumab also demonstrated a generally more favorable safety profile, with adverse events of any grade occurring in 73.4% of patients, compared with 90% of those treated with chemotherapy.
Grade 3 or 4 adverse events and treatment-related deaths were also lower in the pembrolizumab arm, at 26.6% vs. 53.3%.
Jean-Charles Soria, MD, chair of drug development at Gustave Roussy Cancer Center in Paris, the invited discussant, noted that the “45% objective response rate in first-line non–small cell lung cancer is unheard of, and is achieved with a monotherapy.”
“Pembrolizumab clearly leads to a higher objective response, a longer duration of response, a lower frequency of adverse events, better PFS, better OS, compared to chemotherapy.”
“We have, probably, a new standard of care” for patients with high PD-L1 expression and no targetable mutations,” he said.