According to phase 3 study results, the combination of pembrolizumab and chemotherapy can induce high rates of response in patients with gastroesophageal junction adenocarcinoma while maintaining safety.
Neoadjuvant treatment with the combination of pembrolizumab (Keytruda) and chemotherapy showed a statistically significant improvement in pathological complete response (pCR) rates compared with chemotherapy alone in patients with gastroesophageal junction (GEJ) adenocarcinoma, meeting a primary end point of the phase 3 KEYNOTE-585 clinical trial (NCT03221426).1
Topline results from the study announced in the press release by Merck also showed a slight improvement in event-free survival (EFS), but the numbers did not reach the threshold for statistical significance. Further, another primary end point, overall survival (OS), was not precisely investigated since neoadjuvant pembrolizumab/chemotherapy was not superior to chemotherapy alone in terms of EFS.
The safety profile of the pembrolizumab, as per the topline analysis, was consistent with prior studies. Full results from the topline analysis will be presented at during a future medical meeting.
“While a statistically significant improvement in pathological complete response was observed in this study, we are disappointed that the [pembrolizumab] regimen did not significantly improve event-free survival, a result that underscores the challenges in treating locally advanced resectable gastric cancer,” said Scot Ebbinghaus, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “Innovative research in earlier stages of cancer is critical to help patients achieve better outcomes, and our efforts continue in earnest.”
KEYNOTE-585 is a randomized, double-blind study in which pembrolizumab 200 mg is given via intravenous (IV) infusion, every 3 weeks with chemotherapy. The chemotherapy agents used in the study include cisplatin 80 mg/m2 via IV infusion on day 1, oral capecitabine 1000 mg/m2 on days 1 to 14, or cisplatin 80 mg/m2 via IV infusion on day with 5-fluorouracil on day 1. All neoadjuvant treatment in the study is administered in 3-week cycles. In the control arm, patients received matching chemotherapy alone.2
Other primary end points to be explored in the KEYNOTE-585 include the percentage of patients with adverse events (AEs), and the percentage of patients who discontinue treatment because of AEs. The secondary end points of the study include the percentage of patients who experience at least 1 AE, the percentage of patients who discontinue study treatment due to toxicity, and disease-free survival.
The study recruited patients with previously untreated gastric of GEJ adenocarcinoma with an ECOG performance status of 0 or 1, and adequate organ function. The study is active at 171 locations worldwide.
1. Merck provides update on phase 3 KEYNOTE-585 trial in locally advanced resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. June 20, 2023. Accessed June 20, 2023. https://tinyurl.com/5554nj7e
2. Study of pembrolizumab (MK-3475) plus chemotherapy versus placebo plus chemotherapy in participants with gastric or gastroesophageal junction (GEJ) adenocarcinoma (MK-3475-585/KEYNOTE-585). ClincalTrials.gov. Updated August 19, 2022. Accessed June 20, 2023. https://clinicaltrials.gov/ct2/show/NCT03221426?term=KEYNOTE-585&draw=2&rank=2