The Food and Drug Administration (FDA) has approved Keytruda® (pembrolizumab), a programmed death receptor-1 (PD-1)-blocking antibody, in combination with platinum- and fluoropyrimidine-based chemotherapy for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1-5 cm above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation.
The approval was based on data from the KEYNOTE-590 study (ClinicalTrials.gov: NCT03189719), which evaluated the efficacy and safety of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) chemotherapy vs placebo plus cisplatin and 5-FU chemotherapy as first-line treatment in 749 patients with locally advanced or metastatic esophageal or gastroesophageal junction carcinoma who were not candidates for surgical resection or definitive chemoradiation. The major efficacy outcome measures were overall survival (OS) and progression free survival (PFS).
Results showed a statistically significant improvement in OS for patients randomly assigned to pembrolizumab plus chemotherapy (median OS: 12.4 months [95% CI, 10.5-14.0] vs 9.8 months [95% CI, 8.8-10.8] for chemotherapy; hazard ratio [HR] 0.73; 95% CI, 0.62-0.86; P <.0001). Additionally, PFS was observed to be longer in patients treated with pembrolizumab (6.3 months [95% CI, 6.2-6.9]) compared with chemotherapy (5.8 months [95% CI, 5.0-6.0]) (HR 0.65; 95% CI, 0.55-0.76; P <.0001).
In patients with PD-L1 Combined Positive Score (CPS) of 10 or greater (n=383), the median OS was reported to be 13.5 months (95% CI, 11.1-15.6) for the pembrolizumab arm and 9.4 months (95% CI, 8.0-10.7) for the placebo arm (HR 0.62; 95% CI, 0.49-0.78; P <.0001). Exploratory analysis also revealed that among patients with PD-L1 CPS under 10 (n=347), the median OS was 10.5 months (95% CI, 9.7-13.5) in the pembrolizumab group and 10.6 months (95% CI, 8.8-12.0) in the placebo group (HR 0.86; 95% CI, 0.68-1.10).
The most common adverse reactions reported in patients who received pembrolizumab combination therapy were nausea, constipation, diarrhea, vomiting, stomatitis, fatigue/asthenia, decreased appetite, and weight loss.
“Because esophageal cancer generally has poor survival rates, new first-line therapies are urgently needed for these patients,” said Dr Peter Enzinger, Director, Center for Esophageal and Gastric Cancer, Dana-Farber/Brigham and Women’s Cancer Center. “Today’s approval of this indication for Keytruda introduces a new option, which has shown a superior survival benefit compared to FU and cisplatin alone, for newly diagnosed patients with locally advanced or metastatic esophageal or GEJ carcinoma that is not amenable to surgical resection or definitive chemoradiation, regardless of PD-L1 expression status and tumor histology.”
FDA approves Merck’s Keytruda® (pembrolizumab) plus platinum- and fluoropyrimidine-based chemotherapy for treatment of certain patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) carcinoma. [press release]. Kenilworth, NJ: Merck; March 23, 2021.