3,4ĭata from KEYNOTE-181 supported the July 2019 FDA approval of pembrolizumab in patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1, as determined by an FDA-approved test, with disease progression after 1 or more prior lines of systemic therapy. 2 In KEYNOTE-181, single-agent pembrolizumab led to a median OS of 10.3 months versus 6.7 months with chemotherapy (HR, 0.64), an ORR of 22% versus 7%, respectively, and a median DOR of 9.3 months versus 7.7 months, respectively, in second-line patients with ESCC and a CPS of 10 or higher. ![]() In the KEYNOTE-180 trial, the agent elicited an ORR of 14%, with a median duration of response (DOR) that had not been reached in third-line patients with esophageal squamous cell carcinoma (ESCC) and tumors with a PD-L1 combined positive score (CPS) of 10 or higher. Previously, pembrolizumab has demonstrated antitumor activity with a tolerable toxicity profile when used as monotherapy in patients with advanced or metastatic esophageal cancer in 2 pivotal studies: KEYNOTE-180 (NCT02559687) and KEYNOTE-181 (NCT02564263). “Unfortunately, the standard of care has remained relatively unchanged for a long period of time,” Enzinger said. For the second-line setting, docetaxel, paclitaxel, irinotecan, and ramucirumab (Cyramza) plus or minus paclitaxel for adenocarcinoma, is largely used. “First-line pembrolizumab plus chemotherapy versus chemotherapy plus placebo provided a statistically significant and clinically meaningful improvement in OS, PFS, and ORR in patients with locally advanced unresectable or metastatic esophageal cancer, including gastroesophageal junction carcinoma,” Peter Enzinger, MD, lead investigator and director of the Center for Esophageal and Gastric Cancer at Dana-Farber Cancer Institute, said in a press conference ahead of the meeting.įor patients with advanced esophageal cancer, the standard first-line treatment has been fluoropyrimidine in combination with platinum-based chemotherapy, according to Enzinger. At 12 months, the PFS rates in the investigational and control arms were 25% versus 12%, respectively the 18-month rates were 16% versus 6%, respectively. ![]() The median investigator-assessed PFS per RECIST v1.1 criteria was 6.3 months (95% CI, 6.2-6.9) with pembrolizumab plus chemotherapy versus 5.8 months (95% CI, 5.0-6.0) with chemotherapy alone (HR, 0.65 95% CI, 0.55-0.76 P <.0001). Moreover, the 12-month OS rate with pembrolizumab plus chemotherapy was 51% versus 39% with chemotherapy alone at 24 months, these rates were 28% versus 16%, respectively. The results, which were presented during the 2020 ESMO Virtual Congress, showed that the median OS was 12.4 months (95% CI, 10.5-14.0) in patients who received the chemoimmunotherapy regimen versus 9.8 months (95% CI, 8.8-10.8) in those given chemotherapy alone (HR, 0.73 95% CI, 0.62-0.86 P <.0001). According to topline results from the phase 3 KEYNOTE-590 trial (NCT03189719), frontline pembrolizumab (Keytruda) plus chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rates (ORR) compared with chemotherapy alone in patients with locally advanced unresectable or metastatic esophageal cancer.
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