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 alone or with older perioperative/adjuvant chemotherapy regimens. Primary outcome measures included pathologic complete response (pCR) and major pathologic response (MPR).
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 pCR (61.9% vs 3.7%, odds ratio [OR] = 54.8, P = .002) and MPR (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. Event-free survival and overall survival at 36 months were: 70.4% and 72.7% for ICIs; 50.9% and 79.3% for perioperative FLOT; 77.3% and 81.6% for surgery plus older chemotherapy regimens; and 80.6% and 90.4% for surgery alone.
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 concluded: “In resectable dMMR/MSI-H [gastroesophageal adenocarcinoma], neoadjuvant ICIs significantly increase pathologic response and downstaging versus 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 versus FLOT should drive preoperative treatment choices in clinical high-risk disease. The high proportion of pCR/MPR with ICIs provides rationale for exploring organ-sparing surgery or nonoperative management.”
Filippo Pietrantonio, MD, of the Department of Medical Oncology, Istituto Nazionale Tumori IRCCS, Milan, Italy, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gruppo Oncologico del Nord Ovest. For full disclosures of all study authors, visit ascopubs.org.
