Frontline Pembrolizumab Plus Chemotherapy Meets OS End Point in HER2-Negative Gastric/GEJ Adenocarcinoma

The combination of pembrolizumab (Keytruda) and physician’s choice of chemotherapy produced a statistically significant overall survival (OS) benefit vs chemotherapy plus placebo in patients with HER2-negative, locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, meeting the primary end point of the phase 3 KEYNOTE-859 trial (NCT03675737).¹

OS benefits were present irrespective of PD-L1 expression. Additionally, pembrolizumab plus chemotherapy generated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall response rate (ORR) compared with chemotherapy alone.

Merck said in a news release detailed findings from the prespecified interim analysis conducted by an independent data monitoring committee will be presented at an upcoming medical meeting and submitted to regulatory authorities.

“Despite improvements in cancer care, advanced gastric cancer continues to have one of the lowest 5-year survival rates, and new interventions are urgently needed. The results from KEYNOTE-859 show the potential of [pembrolizumab] plus chemotherapy to improve survival beyond chemotherapy alone for patients with HER2-negative, locally advanced, unresectable or metastatic gastric or GEJ adenocarcinoma, regardless of PD-L1 expression,” Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer, Merck Research Laboratories, stated in a press release.

“We are excited by these new results that demonstrate our commitment to exploring new treatment options for patients fighting gastrointestinal cancers with [pembrolizumab] and thank all investigators and patients who participated in this trial.”

The randomized, double-blind KEYNOTE-859 trial enrolled patients with a histologically or cytologically confirmed diagnosis HER2-negative, locally advanced, unresectable or metastatic gastric or GEJ adenocarcinoma with a known PD-L1 expression status.² Patients were also required to have measurable disease per RECIST v1.1 criteria, provide a tissue sample for PD-L1 and microsatellite biomarker analysis, have an ECOG performance status of 0 or 1, and have adequate organ function.

Previous therapy for locally advanced, unresectable or metastatic gastric or GEJ adenocarcinoma was not permitted, although prior neoadjuvant and/or adjuvant therapy was allowed if completed at least 6 months prior to randomization.

Other key exclusion criteria included squamous cell or undifferentiated gastric cancer; major surgery, open biopsy, or significant injury within 28 days of randomization; preexisting peripheral neuropathy greater than grade 1; or known active central nervous system metastases and/or carcinomatous meningitis.

Enrolled patients were randomly assigned to 200 mg of intravenous (IV) pembrolizumab or placebo once every 3 weeks for up to 35 cycles, plus physician’s choice of chemotherapy. Chemotherapy consisted of IV cisplatin at 80 mg/m2 once every 3 weeks plus 5-fluorouracil at 800 mg/m2 via continuous IV on days 1 to 5 of every 3-week cycle, or IV oxaliplatin at 130 mg/m2 once every 3 weeks plus oral capecitabine at 1000 mg/m2 twice daily on days 1 to 14 of every 3-week cycle. Patients in the pembrolizumab arm who achieved a complete response but progressed after discontinuation were permitted to begin a second course of pembrolizumab for up to 17 cycles.

Along with the primary end point of OS, secondary end points included PFS, ORR, duration of response, and safety.

Regarding safety, the safety profile of pembrolizumab was consistent with data from previously reported studies, and no new safety signals were identified.

References

1. Merck announces phase 3 KEYNOTE-859 trial met primary endpoint of overall survival in patients with HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. November 22, 2022. Accessed November 22, 2022. http://bit.ly/3AEyUH0
2. Pembrolizumab (MK-3475) plus chemotherapy versus placebo plus chemotherapy in participants gastric or gastroesophageal junction (GEJ) adenocarcinoma (MK-3475-859/KEYNOTE-859). ClinicalTrials.gov. Updated August 17, 2022. Accessed November 22, 2022. https://clinicaltrials.gov/ct2/show/NCT03675737