This is the first time an anti-PD-1 therapy has demonstrated a survival benefit in this patient population.
Second-line treatment with pembrolizumab (Keytruda, Merck) reduced the risk of death by 31% in patients with advanced esophageal cancer compared with chemotherapy, according to new data from the KEYNOTE-181 phase 3 trial.
An estimated 17,650 adults in the United States will be diagnosed with esophageal cancer this year, with more than 572,000 estimated new cases worldwide, according to Merck. Patients diagnosed with the disease often face a poor prognosis, indicating the need for new therapeutic options.
The trial evaluated pembrolizumab monotherapy as a second-line treatment compared with chemotherapy in more than 628 patients with advanced or metastatic esophageal or esophagogastric junction carcinoma. Patients received either a 200-mg fixed dose of pembrolizumab every 3 weeks or chemotherapy regimens, including docetaxel, paclitaxel, or irinotecan. Of these patients, 401 had squamous cell carcinoma and 222 had a PD-L1 Combined Positive Score (CPS) of ≥10.
Among patients with squamous cell carcinoma, the median overall survival (OS) was 8.2 months for those treated with pembrolizumab compared with 7.1 months in the chemotherapy group. In patients whose tumors expressed PD-L1 with a CPS of ≥10, the median OS in the pembrolizumab group was 9.3 months compared with a median OS of 6.7 months in the chemotherapy group. The estimated 12-month OS rate in these patients was 43% for pembrolizumab versus 20% for chemotherapy, according to the data. Compared with chemotherapy, treatment with pembrolizumab reduced the risk of death by 31%.
“The prognosis for patients diagnosed with esophageal cancer is poor, and for those who experience disease progression, there is no established standard of care, underscoring the need for improved therapies in the second-line setting,” Takashi Kojima, a professor at the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital, said in a statement. “The significant improvement in overall survival observed with Keytruda in patients with squamous cell carcinoma or adenocarcinoma whose tumors expressed PD-L1 with a CPS of 10 or greater represents an important scientific advancement and has the potential to benefit patients who currently have limited treatment options.”
Overall, the safety of pembrolizumab in the study was consistent with previous trials. Treatment-related adverse events occurred in 64.3% of patients taking pembrolizumab compared with 86.1% for chemotherapy, with most common adverse events being fatigue, hypothyroidism, decreased appetite, asthenia, nausea, and diarrhea.
This is the first time an anti-PD-1 therapy has demonstrated a survival benefit for this patient population, according to Merck.
Merck’s Keytruda (pembrolizumab) Reduced Risk of Death by 31 Percent Compared to Chemotherapy in Previously Treated Patients with Advanced Esophageal or Esophagogastric Junction Carcinoma Whose Tumors Expressed PD-L1(CPS ≥10) [news release]. Merck’s website. https://www.mrknewsroom.com/news-release/oncology/mercks-keytruda-pembrolizumab-reduced-risk-death-31-percent-compared-chemother. Accessed January 15, 2019.