Trial results for pembrolizumab (Keytruda) in combination with chemotherapy for gastric or gastroesophageal junction (GEJ) adenocarcinoma were posted on ClinicalTrials.gov on 2025-02-20. The study demonstrated that the pembrolizumab regimen significantly extended median event-free survival (EFS) to 44.4 months compared to 25.7 months for chemotherapy alone.
Background
Pembrolizumab is an immunotherapy drug. Gastric cancer and gastroesophageal junction (GEJ) adenocarcinoma are aggressive malignancies that often present with poor prognosis, highlighting the need for effective treatment strategies.
Trial design
The completed Phase 3 study, NCT03221426 (KEYNOTE-585), enrolled 1007 participants with Gastric Cancer or Gastroesophageal Junction Cancer. The trial evaluated pembrolizumab plus chemotherapy (cisplatin, capecitabine, or 5-fluorouracil) against placebo plus chemotherapy. The primary study hypothesis was that neoadjuvant and adjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, would be superior to neoadjuvant and adjuvant placebo plus chemotherapy, followed by adjuvant placebo, in terms of Event-free Survival (EFS) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Key results
Key results from the trial include:
- Event-free Survival (EFS): The median EFS for the pembrolizumab plus chemotherapy arm was 44.4 months, compared to 25.7 months for the placebo plus chemotherapy arm. A Log Rank analysis yielded a Hazard Ratio (HR) of 0.81 (95% Confidence Interval: 0.67, 0.98) with a p-value of 0.01501.
- Pathological Complete Response (pathCR) Rate: The pathCR rate was 13.4% in the pembrolizumab plus chemotherapy arm, versus 2.0% in the placebo plus chemotherapy arm. The difference in percentage was 11.4% (95% Confidence Interval: 8.0, 15.3) with a p-value of 1e-05.
- Overall Survival (OS): Median OS was 71.8 months for the pembrolizumab plus chemotherapy arm and 55.7 months for the placebo plus chemotherapy arm. The Log Rank analysis showed a Hazard Ratio (HR) of 0.86 (95% Confidence Interval: 0.71, 1.06) with a p-value of 0.07503.
- Adverse Events (AEs): In the pembrolizumab plus XP/FP arm, 396 participants experienced one or more AEs, compared to 398 participants in the placebo plus XP/FP arm. For the FLOT cohorts, 99 participants in the pembrolizumab arm and 103 in the placebo arm experienced AEs. Discontinuations due to AEs were 37 participants in the pembrolizumab plus FLOT cohort and 26 in the placebo plus FLOT cohort.
What this means
The significant improvement in median event-free survival and pathological complete response rates observed with pembrolizumab plus chemotherapy suggests a clinical benefit for patients with gastric or gastroesophageal junction adenocarcinoma. While overall survival showed a numerical advantage for the pembrolizumab arm, it did not reach statistical significance in this analysis. These findings indicate that the addition of pembrolizumab to chemotherapy can delay disease progression and enhance pathological response in this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03221426, titled "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)," were posted on 2025-02-20 on clinicaltrials.gov.