NEW YORK – Merck said on Tuesday that the European Commission has approved pembrolizumab (Keytruda) plus chemotherapy as a first-line treatment for patients with advanced esophageal cancer or HER2-negative gastroesophageal junction cancers whose tumors express PD-L1 with a combined positive score of at least 10.
The approval, which makes the treatment available to this patient population across the European Union's 27 member states plus Iceland, Lichtenstein, Norway, and Northern Ireland, is based on the results of the Phase III Keynote-590 trial.
The trial randomized 749 patients with advanced esophageal or GEJ cancer to receive either pembrolizumab plus chemotherapy or chemo alone. In a pre-specified analysis of patients whose tumors had a PD-L1 combined positive score of at least 10, after a median follow-up of 13.5 months, the median overall survival among patients treated with the pembrolizumab combination was 13.5 months versus 9.4 months among patients who received just chemo. The median progression-free survival times were 7.5 months versus 5.5 months for those receiving the combination and chemo, respectively.
Among patients included in the pre-specified analysis, the pembrolizumab combination reduced patients' risk of death by 38 percent and their risk of disease progression or death by 49 percent versus chemotherapy alone. In the all-comer population, the pembrolizumab combination also improved these outcomes compared to chemo, but the benefits were more pronounced among the PD-L1-expressing population.
In contrast to the European Commission's decision to narrow the approved indication in this setting using patients' PD-L1 status, the FDA also relied on KEYNOTE-590 data, and in March approved the pembrolizumab-chemotherapy regimen for the broader population of patients with metastatic or locally advanced esophageal or GEJ tumors who cannot have surgical resection or definitive chemoradiation.
The EC's approval is backed by a positive recommendation from the European Medicines Agency's Committee for Medicinal Products for Human Use last month. The EMA is also reviewing an application for BMS's checkpoint inhibitor nivolumab (Opdivo) in combination with chemotherapy as first-line treatment for certain gastric, esophageal, and GEJ patients, though with a lower PD-L1 expression cutoff than Merck's combination.