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The National Medical Products Administration in China has approved pembrolizumab (Keytruda) for use in combination with platinum- and fluoropyrimidine-based chemotherapy for the frontline treatment of patients with locally advanced unresectable or metastatic esophageal carcinoma or gastroesophageal junction (GEJ) cancer.

The approval is based on findings from the phase 3 KEYNOTE-590 trial (NCT03189719), in which pembrolizumab demonstrated a statistically significant improvement in progression-free and overall survival (OS) vs 5-fluorouracil (5-FU) and cisplatin alone in this patient population. The median OS was 12.4 months (95% CI, 10.5-14.0) with pembrolizumab compared with 9.8 months (95% CI, 8.8-10.8) for chemotherapy alone (HR, 0.73; 95% CI, 0.62-0.86; 

Additionally, the median progression-free survival (PFS) was 6.3 months (95% CI, 6.2-6.9) and 5.8 months (95% CI, 5.0-6.0), respectively, in the overall population.

“Compared to the rest of the world, China has a disproportionate number of patients who are diagnosed with and who die from esophageal cancer, the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in the country,” said Shen Lin, MD, vice president, Clinical Oncology, Beijing Cancer Hospital and Peking University, and deputy director, Beijing Institute for Cancer Research in China. “This approval for Keytruda provides an important new option to patients with advanced esophageal carcinoma in China who currently have limited available treatment options in the first-line setting.”

Safety findings of 51 Chinese patients with esophageal carcinoma enrolled on the study showed that the profile of pembrolizumab in this population was consistent with prior safety data with the PD-1 inhibitor.

Pembrolizumab is also approved in China as a second-line treatment for select patients with locally advanced or metastatic esophageal squamous cell carcinoma whose tumors express PD-L1 (≥10).

In the multicenter, double-blind, placebo-controlled KEYNOTE-590 trial, 749 patients with locally advanced unresectable or metastatic esophageal or GEJ carcinoma (Siewert type I) who were ineligible for surgery or definitive chemoradiation were randomized 1:1 to receive cisplatin at 80 mg/m2 on day 1 every 3 weeks for up to 6 cycles plus 5-FU at 800 mg/m2 daily on days 1 to 5 every 3 weeks, with or without pembrolizumab at 200 mg on day 1 every 3 weeks. 5-FU could also be given per local standard for up to 2 years. All treatment was given intravenously.

To be eligible for enrollment, patients had to have metastatic esophageal cancer or esophageal squamous cell carcinoma, be treatment naïve, have an ECOG performance status of 0 or 1, and have measurable disease. Patients were stratified based on region (Asia vs non-Asia), disease (ESCC vs esophageal cancer), and performance status (0 vs 1).

The primary end points were investigator-assessed PFS and OS via RECIST v1.1 criteria in the overall study population, in those with PD-L1 expression (combined positive score ≥10), and in those with squamous histology. Secondary end points included investigator-assessed objective response rate and duration of response.

“In China, esophageal and gastroesophageal junction cancers are leading causes of death, and there have been few treatment advances for patients over the past several decades,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, the developer of pembrolizumab. “With this approval of Keytruda plus chemotherapy – the first for an anti-PD-1 regimen in the first-line setting – we can now provide patients with an immunotherapy treatment option earlier in the course of treatment that has been shown to significantly improve survival.”

In March 2021, the FDA approved pembrolizumab for use in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal carcinoma who are ineligible for surgical resection or definitive chemoradiation. The decision was also based on the phase 3 KEYNOTE-590 findings.

Merck’s KEYTRUDA® (pembrolizumab) Approved in China in Combination With Chemotherapy for First-Line Treatment of Patients With Locally Advanced Unresectable or Metastatic Esophageal or Gastroesophageal Junction (GEJ) Carcinoma. News release. Merck. September 7, 2021. Accessed September 7, 2021. https://bit.ly/3kXmZeC

Kato K, Sun J-M, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: the phase 3 KEYNOTE-590 study. 

. 2020;31(suppl 4):S1192-S1193. doi:10.1016/j.annonc.2020.08.2298

Articles

The National Medical Products Administration in China has approved pembrolizumab for use in combination with platinum and fluoropyrimidine-based chemotherapy for the frontline treatment of patients.