Pembrolizumab Plus Chemotherapy in KEYNOTE-590 at 5 Years

Key Takeaways

• Long-term overall survival remained higher with pembrolizumab plus chemotherapy during extended follow-up.
• Progression-free survival findings also favored the pembrolizumab-containing regimen over time.
• Grade 3 or higher treatment-related adverse events were frequent in both groups, no new safety signals were reported, and investigators stated that pembrolizumab plus chemotherapy supported first-line treatment for previously untreated advanced esophageal cancer with PD-L1 combined positive score 1 or higher.

In the 5-year extended follow-up of KEYNOTE-590, long-term overall survival remained separated in previously untreated advanced esophageal cancer or Siewert type 1 gastroesophageal junction cancer. Five-year overall survival was 10.6% with pembrolizumab plus chemotherapy and 3.0% with placebo plus chemotherapy. This randomized phase III comparison updated long-term outcomes for pembrolizumab plus chemotherapy versus placebo plus chemotherapy.

The trial enrolled adults with previously untreated advanced esophageal cancer or Siewert type 1 gastroesophageal junction cancer. Participants were assigned 1:1 to pembrolizumab plus chemotherapy or placebo plus chemotherapy in this randomized phase III study. The analyzed population included 749 participants, with 373 in the pembrolizumab group and 376 in the placebo group. Median follow-up reached 58.8 months, with a range of 49.2 to 70.6 months, allowing long-term efficacy and safety assessment.

Median overall survival was 12.3 months with pembrolizumab plus chemotherapy and 9.8 months with placebo plus chemotherapy. The overall survival hazard ratio was 0.72, with a 95% confidence interval from 0.62 to 0.84. These findings added detail to the 5-year separation between study groups, and the overall survival advantage remained present across the extended follow-up analysis.

Progression-free survival also favored pembrolizumab plus chemotherapy in the long-term analysis. Median progression-free survival was 6.3 months with pembrolizumab plus chemotherapy and 5.8 months with placebo plus chemotherapy. The progression-free survival hazard ratio was 0.64, with a 95% confidence interval from 0.54 to 0.75. Five-year progression-free survival was 5.5% in the pembrolizumab arm and not reached in the comparator arm, indicating sustained disease control over time.

Grade 3 or higher treatment-related adverse events occurred in 71.9% of participants receiving pembrolizumab plus chemotherapy and 67.6% receiving placebo plus chemotherapy. In the 5-year follow-up, investigators reported no new safety signals alongside the long-term efficacy findings. They stated that the data showed durable efficacy after 5 years and that pembrolizumab plus chemotherapy supported first-line treatment for previously untreated advanced esophageal cancer with PD-L1 combined positive score 1 or higher.