FDA Approves Pembrolizumab for Advanced Esophageal or GEJ Cancer

FDA

The FDA has approved pembrolizumab (Keytruda) 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 regulatory decision was based on data from the KEYNOTE-590 (NCT03189719), which enrolled a total of 749 patients with metastatic or locally advanced esophageal or gastroesophageal junction carcinoma who were ineligible for surgical resection or definitive chemoradiation.

To be eligible for enrollment, patients needed to have metastatic esophageal cancer or esophageal squamous cell carcinoma (ESCC), 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).²

Participants were randomized 1:1 to receive either pembrolizumab at 200 mg every 3 weeks plus cisplatin at 80 mg/m² every 3 weeks plus fluorouracil at 800 mg/m² on days 1 through 5 every 3 weeks or placebo with cisplatin/fluorouracil at the same dose and schedule. Treatment was administered until either intolerable toxicity or progressive disease.

The co-primary end points for the trial included overall survival (OS) and progression-free survival (PFS), per investigator assessment and RECIST v1.1 criteria. Secondary end points included objective response rate (ORR) per investigator assessment and RECIST v1.1 criteria.

Results indicated that pembrolizumab plus chemotherapy led to a statistically significant improvement in both OS and PFS. Specifically, the median OS in the investigative arm was 12.4 months (95% CI, 10.5-14.0) vs 9.8 months (95% CI, 8.8-10.8) in the control arm (hazard ratio [HR] 0.73; 95% CI, 0.62-0.86; P <.0001). In patients who had a PD-L1 combined positive score (CRPS) of 10 or higher, the median OS with the pembrolizumab regimen was 13.5 months (95% CI, 11.1-15.6) vs 9.4 months (95% CI, 8.0-10.7) with chemotherapy alone (HR, 0.63; 95% CI, 0.49-0.78; P <.0001).

Moreover, the median PFS with pembrolizumab/chemotherapy was 6.3 months (95% CI, 6.2-6.9) vs 5.8 months with chemotherapy alone (95% CI, 5.0-6.0), (HR 0.65; 95% CI, 0.55-0.76; P<.0001). In those with a PD-L1 CPS of 10 or higher, the median PFS in the investigative and control arms was 7.5 months (95% CI, 6.2-8.2) vs 5.5 months (95% CI, 4.3-6.0), respectively (HR, 0.51; 95% CI, 0.41-0.65; P <.0001). In the subgroup of patients with ESCC, the HR was 0.65 (95% CI, 0.54-0.78; P <.0001).

Additional data presented during the 2020 ESMO Virtual Congress showed that the ORR was 45.0% (95% CI, 39.9%-50.2%) with pembrolizumab/chemotherapy vs 29.3% (95% CI, 24.7%-34.1%) with chemotherapy alone (P <.0001). The median duration of response in the investigative and control arms was 8.3 months and 6.0 months, respectively.

Regarding safety, the common adverse effects experienced by patients who received the pembrolizumab regimen included nausea, constipation, diarrhea, vomiting, stomatitis, fatigue/asthenia, decreased appetite, and weight loss.

References

1. FDA approves pembrolizumab for esophageal or GEJ carcinoma. News release. FDA. March 22, 2021. Accessed March 22, 2021. http://bit.ly/31908Di
2. 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. Ann Oncol. 2020;31(suppl 4):S1192-S1193. doi:10.1016/j.annonc.2020.08.2298