Pembrolizumab improves OS in advanced, PD-L1–positive oesophageal cancer
Second-line treatment with pembrolizumab is shown to significantly improve overall survival (OS) vs chemotherapy in patients with advanced or metastatic oesophageal cancer in the phase III KEYNOTE-181 study.
The results showed a 2.6-month improvement in OS with pembrolizumab in patients with a PD-L1 combined positive score (CPS) of ≥10 compared with investigator’s choice of chemotherapy with paclitaxel, docetaxel or irinotecan. [Kojima, T, et al, ASCO GI 2019, abstract 2]
In the 222 patients with a PD-L1 CPS of ≥10, median OS was 9.3 months in the pembrolizumab group vs 6.7 months in the chemotherapy group (hazard ratio [HR], 0.69; 95 percent confidence interval [CI], 0.52 to 0.93; p=0.0074).
“At 12 months, OS rate was 43 percent vs 20 percent in these patients with high levels of PD-L1 expression,” reported lead study author Professor Takashi Kojima of the National Cancer Center Hospital East in Kashiwa, Japan.
“Among 401 patients with squamous cell carcinoma [SCC], there was a clinically meaningful but not statistically significant improvement in OS with pembrolizumab vs chemotherapy,” said Kojima.
Median OS in the SCC cohort was 8.2 months with pembrolizumab compared with 7.1 months with chemotherapy (HR, 0.78; 95 percent CI, 0.63 to 0.96; p=0.0095), but the between-group difference did not reach statistical significance per prespecified boundaries.
Similarly, in the intention-to-treat (ITT) population (n=628), OS did not differ significantly between the pembrolizumab and chemotherapy groups (median, 7.1 months vs 7.1 months; HR, 0.89; 95 percent CI, 0.75 to 1.05; p=0.0560).
In the study, patients with advanced or metastatic SCC or adenocarcinoma of the oesophagus or Siewert type I adenocarcinoma of the esophagogastric junction that had progressed after standard first-line therapy were randomized in a 1:1 ratio to receive pembrolizumab (200 mg Q3W) for up to 2 years or investigator’s choice of paclitaxel, docetaxel or irinotecan. Randomization was stratified by histology (SCC vs adenocarcinoma) and geographic region (Asia vs rest of the world).
Patients were followed up for a median of 7.1 months in the pembrolizumab group vs 6.9 months in the chemotherapy group. Primary endpoints were OS in the SCC, PD-L1 CPS ≥10, and ITT populations.
“In addition to OS, progression-free survival [PFS] was also improved with pembrolizumab vs chemotherapy in patients with a PD-L1 CPS of ≥10, with a PFS rate of 21 percent vs 7 percent,” reported Kojima. “In the SCC cohort, PFS rate was 15 percent vs 9 percent. In the ITT population, PFS rate was 12 percent vs 10 percent.”
Overall response rates were also higher with pembrolizumab vs chemotherapy, at 21.5 percent vs 6.5 percent in those with a PD-L1 CPS of ≥10, 16.7 percent vs 7.4 percent in those with SCC, and 13.1 percent vs 7.1 percent in the ITT population.
Adverse events (AEs) of any grade or grade 3–5 were less frequent with pembrolizumab than chemotherapy (any grade, 64 percent vs 86 percent; grade 3–5, 18 percent vs 41 percent).“These findings support pembrolizumab as a new second-line standard of care for oesophageal cancer in patients with a PD-L1 CPS of ≥10,” said Kojima. “The phase III KEYNOTE-590 study is ongoing to evaluate pembrolizumab in combination with chemotherapy as first-line treatment for patients with advanced oesophageal cancer.”