Details

Autor(en) / Beteiligte

• Fucà, Giovanni
• Cohen, Romain
• Lonardi, Sara
• Shitara, Kohei
• Elez, Maria Elena
• Fakih, Marwan
• Chao, Joseph
• Klempner, Samuel J
• Emmett, Matthew
• Jayachandran, Priya
• Bergamo, Francesca
• García, Marc Díez
• Mazzoli, Giacomo
• Provenzano, Leonardo
• Colle, Raphael
• Svrcek, Magali
• Ambrosini, Margherita
• Randon, Giovanni
• Shah, Aakash Tushar
• Salati, Massimiliano
• Fenocchio, Elisabetta
• Salvatore, Lisa
• Chida, Keigo
• Kawazoe, Akihito
• Conca, Veronica
• Curigliano, Giuseppe
• Corti, Francesca
• Cremolini, Chiara
• Overman, Michael
• Andre, Thierry
• Pietrantonio, Filippo

Titel

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

Ist Teil von

• Journal for immunotherapy of cancer, 2022-02, Vol.10 (2), p.e004001

Ort / Verlag

England: BMJ Publishing Group Ltd

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• BackgroundDespite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs.MethodsWe conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset.ResultsThe mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement.ConclusionsPatients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches.