In an individual-patient pooled analysis reported in the Journal of Clinical Oncology, Raimondi et al found that neoadjuvant treatment with dual CTLA-4/PD-(L)1 immune checkpoint inhibitors (ICIs) was associated with higher pathologic response rates vs perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) in patients with deficient mismatch repair (dMMR)/microsatellite instability–high (MSI-H) resectable gastroesophageal adenocarcinoma.
Study Details
The study included 197 patients from seven clinical trials who received: neoadjuvant dual CTLA-4/PD-(L)1 ICIs with or without surgery, perioperative FLOT and surgery, and surgery with or without older perioperative/adjuvant chemotherapy regimens. Primary outcome measures included pathologic complete response and major pathologic response.
Key Findings
Among the 197 patients, 49 received ICIs, 27 received FLOT, 33 received surgery alone, and 88 received older chemotherapy regimens.
Among 69 patients who underwent surgery after ICIs or FLOT, those receiving ICIs had significantly higher pathologic complete response rates (61.9% vs 3.7%; odds ratio [OR] = 54.8; P = .002) and major pathologic response rates (78.6% vs 10.0%; OR = 39.3; P < .001), as well as higher rates of pN0 (OR = 4.2; P = .015) and pT0-2 (OR = 16.4; P < .001).
No significant differences in event-free survival or overall survival were observed.
Among all patients, residual nodal disease (ypN1) or ypT4 status after neoadjuvant ICIs or FLOT and an absence of pathologic response were associated with poorer progression-free and overall survival.
The investigators, including corresponding author Filippo Pietrantonio, MD, of the Department of Medical Oncology, Istituto Nazionale Tumori IRCCS, Milan, Italy, concluded: “In resectable dMMR/MSI-H [gastroesophageal adenocarcinoma], neoadjuvant ICIs significantly increase pathologic response and downstaging vs FLOT, with comparable [event-free survival/overall survival] with surgery with or without chemotherapy. The higher proportion of ypN0 and lack of ypT4 after neoadjuvant ICIs vs FLOT should drive preoperative treatment choices in clinical high-risk disease. The high proportion of [pathological complete responses/major pathological responses] with ICIs provides rationale for exploring organ-sparing surgery or nonoperative management.”
Raimondi A, et al: J Clin Oncol 43:3457-3467, 2025.