KEYNOTE-585
Trial question
What is the role of neoadjuvant and adjuvant pembrolizumab in patients with untreated, locally advanced resectable gastric or gastroesophageal cancer?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
28.0% female
72.0% male
N = 804
804 patients (229 female, 575 male).
Inclusion criteria: adult patients with untreated, locally advanced, resectable gastric or gastroesophageal adenocarcinoma, and an ECOG performance status 0-1.
Key exclusion criteria: non-infectious pneumonitis; active infection requiring systemic therapy; receipt of prior systemic anti-cancer therapy including investigational agents for the current malignancy; immunodeficiency or receipt of chronic systemic corticosteroid therapy.
Interventions
N=402 pembrolizumab (200 mg intravenous pembrolizumab plus cisplatin-based doublet chemotherapy, followed by surgery).
N=402 placebo (intravenous saline plus cisplatin-based doublet chemotherapy, followed by surgery).
Primary outcome
Pathological complete response
12.9%
2%
12.9 %
9.7 %
6.5 %
3.2 %
0.0 %
Pembrolizumab
Placebo
Significant
increase ▲
NNT = 9
Significant increase in pathological complete response (12.9% vs. 2%; AD 10.9%, 95% CI 7.5 to 14.8).
Secondary outcomes
Significant increase in median event-free survival (44.4 months vs. 25.3 months; HR 1.23, 95% CI 1.01 to 1.49).
No significant difference in median overall survival (60.7 months vs. 58 months; HR 1.11, 95% CI 0.9 to 1.37).
Safety outcomes
No significant difference in ≥ 3 grade adverse events and treatment-related serious adverse events.
Conclusion
In adult patients with untreated, locally advanced, resectable gastric or gastroesophageal adenocarcinoma, and an ECOG performance status 0-1, pembrolizumab was superior to placebo with respect to pathological complete response.
Reference
Kohei Shitara, Sun Young Rha, Lucjan S Wyrwicz et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224.
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