Landmark trial results mean pembrolizumab could become a new option for patients with NSCLC (PD-L1 ≥50%)

Pembrolizumab inhibits the PD-1 signalling pathway, which is augmented in some cancers and allows the afflicted cells to evade the immune system. Pembrolizumab is currently indicated second line for locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1. Platinum-based chemotherapies are the current standard of care, first line for NSCLC; they exert their effects through the crosslinking of DNA.

“We now have a better treatment opportunity for those patients with a high PD-L1 expression in their tumour. This is approximately 30% of patients.”
Dr Martin Reck, Chief Oncology Physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany

KEYNOTE-024 aimed to investigate the efficacy of pembrolizumab (300 mg every 3 weeks) versus platinum-based chemotherapy in patients with previously untreated NSCLC. The phase III trial enrolled 305 patients, all of whom highly expressed PD-L1 (defined as ≥50%) but did not have sensitising mutations of the epidermal growth factor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene. PFS was the primary endpoint of the study, measured by RECIST criteria (version 1.1).

“The results have been extremely clear, pembrolizumab was superior to platinum-based chemotherapy. We have seen a significant improvement in PFS, in OS, despite a cross-over of 50%, and we have seen a substantial improvement in response,” Dr Reck explained. Median PFS was 10.3 months with pembrolizumab (95% confidence interval (CI), 6.7 – not reached) versus 6.0 with chemotherapy (95% CI, 4.2-6.2). The hazard ratio (HR) for disease progression or death was 0.50 (95% CI 0.37-0.68, P<0.001).

Secondary endpoints included OS, objective response rate (ORR) and safety. The estimated OS at 6 months was 80.2% with pembrolizumab versus 72.4% with chemotherapy (HR for death 0.60, 95% CI 0.41-0.89, P=0.005).

ORR was also improved in patients receiving pembrolizumab, at 44.8% (n=69) compared to 27.8% (n=42) for those treated with chemotherapy. Median duration of response, an exploratory endpoint, was not yet reached with pembrolizumab (1.9+ to 14.5+ months) and 6.3 months (2.1+ to 12.6+) with chemotherapy.

Fewer treatment-related adverse events (any grade) were reported in patients receiving pembrolizumab compared to chemotherapy (73.4%; n=113 vs 90.0%; n=135). Grade 3-5 events were 26.6% (n=41) with pembrolizumab and 53.3% (n=80) with chemotherapy.

Dr Reck believes that the findings could change current treatment algorithms, “to put this data into our daily clinical practice, we have to see that we now have a better treatment opportunity for those patients with a high PD-L1 expression in their tumour. This is approximately 30% of patients.”

He continues, “in our upfront diagnostic algorithm, we should look for the presence of EGFR mutations and ALK translocations, but now, furthermore, we also should check that these patients do have a high expression of PD-L1, because then we have the new and highly effective treatment with pembrolizumab.”

The paper, ‘Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer’, has now been published in the New England Journal of Medicine.

Based on Reck M, Rodríguez-Abreu D et al. KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% (LBA8_PR). Presented on Sunday 9 October 2016.

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