The FDA has approved pembrolizumab (Keytruda®, Merck Sharp & Dohme Corp.) in combination with platinum/fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal junction (GEJ) carcinoma who do not qualify for surgical resection or definitive chemoradiation.
"Pembrolizumab plus chemotherapy versus chemotherapy was superior for overall survival in patients with esophageal squamous cell carcinoma (ESCC) with a combined positive score (CPS) ≥10 and all patients," wrote Ken Kato, MD, PhD, of the National Cancer Center Hospital, Tokyo, in their September publication of results of the phase 3 KEYNOTE-590 trial (NCT03189719), on which the approval was based. "Progression-free survival was superior with pembrolizumab plus chemotherapy versus chemotherapy in ESCC, CPS ≥10, and all patients."
KEYNOTE-590 enrolled 749 patients with metastatic or locally advanced esophageal or GEJ carcinoma who did not qualify for surgical resection or definitive chemoradiation. Patients were randomized in a 1:1 ratio to receive either pembrolizumab 200 mg or placebo every three weeks for up to two years, plus cisplatin 80 mg/m2 on Day One of six three-week cycles and 5-fluorouracil 800 mg/m2 on Day One of five three-week cycles. The primary end points were overall survival and progression-free survival, with the secondary end point of objective response rate.
At a median follow-up of 10.8 months, pembrolizumab/chemotherapy prolonged both median overall survival (12.4 vs 9.8 months) and median progression-free survival (6.3 vs 5.8 months) compared with placebo/chemotherapy. In addition, pembrolizumab resulted in a higher objective response rate (45.0% vs 29.3%) and a longer median duration of response (8.3 vs 6.0 months).
The most common adverse events occurring in at least 20% of patients who had been treated with pembrolizumab were nausea, constipation, diarrhea, vomiting, fatigue/asthenia, decreased appetite, and weight loss. Grade 3 to 5 drug-related adverse events occurred in 72% of patients in the pembrolizumab group, compared with 68% in the placebo group. The pembrolizumab group also had a higher rate of treatment discontinuation due to drug-related adverse events (19% vs 12%).
"Pembrolizumab plus chemotherapy provided superior overall survival, progression-free survival, and objective response rate versus chemotherapy, with a manageable safety profile in patients with untreated, advanced esophageal and GEJ cancer," concluded Dr. Kato and colleagues in their publication in Annals of Oncology. "These data demonstrate that first-line pembrolizumab plus chemotherapy is a new standard of care in this population."
The recommended pembrolizumab dose for esophageal cancer is 200 mg every three weeks or 400 mg every six weeks.
For More Information
Kato K, Sun J, Shah MA, et al (2020). Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: the phase 3 KEYNOTE-590 study. Ann Oncol, 31(suppl_4):S1142-S1215. DOI:10.1016/annonc/annonc325
US Food & Drug Administration (2021). FDA approves pembrolizumab for esophageal or GEJ carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-esophageal-or-gej-carcinoma?utm_medium=email&utm_source=govdelivery
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