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Pembrolizumab plus chemotherapy prolonged survival among patients with previously untreated advanced esophageal or esophagogastric junction (EGJ) cancer, according to results of the phase 3 KEYNOTE-590 trial presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.
“Pembrolizumab plus chemotherapy should be a new standard of care as first-line therapy in patients with locally advanced and metastatic esophageal including EGJ adenocarcinoma,” Ken Kato, MD, PhD, of the National Cancer Center Hospital in Japan, and presenter of the study, said.
The international, double-blind, phase 3 KEYNOTE-590 trial randomly assigned 749 patients with locally advanced/unresectable or metastatic esophageal or EGJ cancer to receive pembrolizumab plus chemotherapy or placebo plus chemotherapy. Both adenocarcinoma and squamous cell carcinoma (ESCC) of the esophagus were included. There was no crossover.
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The primary coprimary endpoints included overall survival (OS) and progression-free survival (PFS) among all patients and was stratified by PD-L1 expression level. The secondary endpoints included objective response rate (ORR). These data represent the final analysis for PFS and interim analysis for OS.
At baseline, the median patient age was 63 years, and 83% of patients were male. Recruitment from Asia represented 52% of the cohort. The majority of patients had metastatic disease (91%) and squamous cell carcinoma (73%). PD-L1 positivity of CPS ≥10 was present in 51% of patients.
Pembrolizumab plus chemotherapy resulted in a substantially higher ORR at 45.0% compared with 29.3% with chemotherapy (P<.0001), with a median duration of response of 8.3 or 6.0 months, respectively.
Among patients with ESCC, pembrolizumab plus chemotherapy resulted in significantly improved OS with a median of 13.9 months compared with 8.8 months with chemotherapy (hazard ratio [HR], 0.57; 95% CI, 0.43-0.75; P <.0001) among patients with a PD-L1 combined positive score (CPS) of at least 10.
The 12-month and 24-month rates of OS were 55% and 31%, respectively, for pembrolizumab plus chemotherapy, compared with 34% and 15%, respectively, for chemotherapy alone. The OS benefit was similar among all patients with ESCC (HR, 0.72; 95% CI, 0.60-0.88; P =.0006).
PFS was also prolonged with pembrolizumab plus chemotherapy, with a median of 6.3 months compared with 5.8 months with chemotherapy (HR, 0.65; 95% CI, 0.55-0.76; P <.0001) among the entire cohort. The 12- and 18-month OS rate was 25% and 16%, respectively, for the pembrolizumab plus chemotherapy arm compared with 12% and 6%, respectively, for the chemotherapy arm.
Among patients with a PD-L1 CPS of 10 or higher, the median PFS was 7.5 months with pembrolizumab plus chemotherapy compared with 5.5 months with chemotherapy (HR, 0.51; 95% CI, 0.41-0.65; P <.0001). A similar PFS benefit was observed among patients with ESCC (HR, 0.65; 95% CI, 0.54-0.78; P <.0001),
The OS and PFS benefits favored pembrolizumab plus chemotherapy across all subgroups.
The rates of treatment-related adverse events (TRAEs) were similar between arms. AEs of grade 3 or higher occurred among 71.9% of patients in the pembrolizumab plus chemotherapy arm compared with 67.6% of patients in the chemotherapy arm. TRAEs in the pembrolizumab plus chemotherapy or chemotherapy arms led to treatment discontinuation among 19.5% and 11.6% of patients, respectively, and 2.4% and 1.4% of patients, respectively, died. Grade 3 or higher immune-mediated AEs occurred in 7% of patients in the pembrolizumab plus chemotherapy arm compared with 2.2% in the chemotherapy arm.
Dr Kato concluded by stating that “first-line pembrolizumab plus chemotherapy vs chemotherapy plus placebo provided a statistically significant and clinically meaningful improvement in OS, PFS, and ORR in patients with locally advanced and metastatic esophageal including EGJ adenocarcinoma.”
Disclosure: Some of the authors of the study reported financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.
Reference
Kato K, Sun J, 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. Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA8_PR.
