Pembrolizumab/Chemo Receives European Approval in First-Line GI Cancers

The approval was based on data from both the phase 3 KEYNOTE-859 study (NCT03675737) and the phase 3 KEYNOTE-966 study (NCT04003636).

The European Commission has granted approval to pembrolizumab (Keytruda) and chemotherapy in 2 gastrointestinal cancer indications, according to a press release from Merck.¹

In particular, pembrolizumab is available in the first line in combination with fluoropyrimidine-/platinum-containing chemotherapy for locally advanced, unresectable, or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma for tumors that express PD-L1 with a combined positive score of 1 or more. Additionally, pembrolizumab can be combined with gemcitabine/cisplatin in the first-line treatment of locally advanced, unresectable, or metastatic biliary tract cancer.

The approval was based on data from both the phase 3 KEYNOTE-859 study (NCT03675737) and the phase 3 KEYNOTE-966 study (NCT04003636).

In the KEYNOTE-859 study, the pembrolizumab/chemotherapy combination yielded overall survival benefit in patients with gastric/GEJ adenocarcinoma that translated to a 22% reduction in risk of death following treatment vs chemotherapy alone (HR, 0.78; 95% CI, 0.70-0.87; P <.0001). Additionally, those with PD-L1 expression experienced a decrease in risk of death by 26% following treatment with the combination vs chemotherapy alone (HR, 0.74; 95% CI, 0.65-0.84; P <.0001).

The median overall survival (OS) in both the general population following treatment with pembrolizumab/chemotherapy vs chemotherapy alone, respectively, was 13.0 months (95% CI, 11.6-14.2) vs 11.4 months (95% CI, 10.5-12.0).

Data from the KEYNOTE-966 trial highlighted a reduction in risk of death of 17% in patients with biliary tract cancer who were treated with pembrolizumab/chemotherapy compared with chemotherapy alone (HR, 0.83; 95% CI, 0.72-0.95; one-sided P = .0034). The median OS in each respective arm was 12.7 months (95% CI, 11.5-13.6) vs 10.9 months (95% CI, 9.9-11.6).

“[Pembrolizumab] has shown its potential as an important treatment option in the [European Union] across a number of gastrointestinal cancers, with seven indications based on data from our extensive clinical development program,” Marjorie Green, MD, senior vice president and head of late-stage oncology and global clinical development at Merck Research Laboratories, said in the press release. “With these two new approvals of KEYTRUDA-based regimens in advanced HER2-negative gastric and gastroesophageal junction cancer and advanced biliary tract cancer, Merck continues to demonstrate progress in providing treatment options to patients in Europe.”

The FDA approved pembrolizumab/chemotherapy for HER2-negative gastric/GEJ adenocarcinoma in November 2023,² as well as in advanced biliary tract cancer in the same month.³

References

1. European Commission approves Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy for new first-line indications in advanced HER2-negative gastric or GEJ adenocarcinoma in tumors expressing PD-L1 (CPS ≥1) and advanced biliary tract cancer. News release. Merck. December 18, 2023. Accessed December 18, 2023. https://bit.ly/3RuyPwT
2. FDA approves pembrolizumab with chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma. News release. FDA. November 16, 2023. Accessed December 18, 2023. https://shorturl.at/acnQ1
3. FDA approved Merck’s Keytruda (pembrolizumab) plus gemcitabine and cisplatin as treatment for patients with locally advanced unresectable or metastatic biliary tract cancer. News release. Merck. November 1, 2023. Accessed December 18, 2023. https://bit.ly/3tXMx3D