The U.S. Food and Drug Administration approved Pembrolizumab (Keytruda) plus fluoropyrimidine- and platinum-containing chemotherapy as the first line treatment for adults

By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY

On November 16, 2023, the U.S. Food and Drug Administration approved Pembrolizumab (Keytruda) plus fluoropyrimidine- and platinum-containing chemotherapy as the first line treatment for adults with locally advanced unresectable or metastatic, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Study ID: NCT03675737

The approval was based on the phase 3 KEYNOTE-859 trial, a multicenter, randomized, double-blind, placebo-controlled study that included  patients with locally advanced or metastatic adenocarcinoma of the stomach or GEJ. Pembrolizumab was given intravenously at 200 mg in combination with the investigator’s choice of chemotherapy until indications to discontinue treatment were present. The median treatment duration was approximately 2 years.

Efficacy was established on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Results of the study showed significant improvements in OS, PFS, and ORR with the use of Pembrolizumab in comparison to chemotherapy alone. The study results revealed that, after a median period of 31.0 months for follow-up (range, 15.3 and 46.3 months), patients who were administered the pembrolizumab had a median OS rate of 12.9 months (95% CI, 11.9-14.0). This was in comparison to a median of 11.5 months (95% CI, 10.6-12.1) for those who were subjected to chemotherapy alone (HR: 0.78; 95% CI, 0.70-0.87; p <.0001). The overall survival rates at the 12- and 24-month marks for the combination treatment were 52.7% and 28.2%, respectively, as opposed to the 46.7% and 18.9% rates observed with chemotherapy alone. The treatment also showed benefits across various subgroups, including geographic region, PD-L1 expression, and choice of chemotherapy.

Side effects of the medication included nausea, diarrhea, anemia, vomiting, low platelet and neutrophil counts, skin discomfort in hands and feet, loss of appetite, fatigue, nerve damage, increased liver enzyme levels, and sensitivity issues in the peripheral nerves. More severe side effects, including those related to the immune system, were more common in patients treated with Pembrolizumab compared to those undergoing chemotherapy alone. Additionally, more patients stopped treatment due to side effects in the Pembrolizumab group.

In summary, the FDA has approved Pembrolizumab for the first-line treatment of adults with locally advanced unresectable or metastatic, HER2-negative gastric or GEJ adenocarcinoma. The recommended dose is 200 mg intravenously in combination with the investigator’s choice of chemotherapy, with the treatment duration lasting approximately 2 years.”