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Resume Bien que la chimiotherapie cytotoxique soit la principale option therapeutique dans le traitement du cancer gastrique en situation metastatique, des agents moleculaires cibles ont ete recemment introduits pour tenter d’ameliorer les resultats de survie globale qui, en moyenne, ne depassent pas 1 an. Le trastuzumab et le ramucirumab, anticorps diriges, respectivement, contre HER2 et VEGFR2 peuvent ainsi representer un interet pour certains patients. Les resultats de diverses etudes cliniques montrent que les patients asiatiques ont des survies globales superieures aux patients caucasiens. Les differences existantes entre les populations et notamment l’existence de polymorphismes capables d’influencer la biodisponibilite du fluorouracil ont ete suggerees comme de possibles explications. L’histologie, les procedures chirurgicales, l’administration d’une therapie neoadjuvante en Occident ainsi que les programmes de depistage en Asie constituent d’autres facteurs susceptibles d’influer sur la survie des patients. Cependant, aucun de ces differents elements ne peut expliquer seul ce phenomene. L’objectif de cet article est de presenter les principaux protocoles utilises en pratique clinique, les perspectives de traitement du cancer gastrique metastatique et les particularites observees chez les patients asiatiques et caucasiens.

Simple Summary Several studies suggested an enhanced efficacy of conventional treatments (CT, i.e., chemotherapy +/− targeted therapy) administered after immune checkpoint inhibitors (ICI) in certain tumor types, but no data are available concerning metastatic colorectal cancer (mCRC) patients harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). The aim of our study was to assess the outcomes of dMMR/MSI mCRC patients receiving CT after ICI failure. We retrospectively collected clinical data from a multicentric cohort of 31 patients. Although limited by the small number of patients, our results did not suggest improved outcomes with CT in our population, and no significant association with previous ICI efficacy or with anti-VEGF agents was evidenced. However, prolonged disease control was observed in several cases, suggesting that some patients might derive an unexpected benefit from post-ICI treatments. With ICI becoming the standard of care in patients newly diagnosed with dMMR/MSI mCRC, these results might help to inform clinical decision-making and to guide future therapeutic strategies for these patients. Abstract Background: Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure. Methods: We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020. Results: 31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1–21.3 months) was observed in 4 pts (13%). Conclusions: Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.

Although cytotoxic chemotherapy is the main therapeutic option to treat gastric cancer in the metastatic setting, molecular targeted agents have recently been introduced in an effort to improve survival outcomes which in average do not exceed 1 year. Trastuzumab and ramucirumab, antibodies directed against HER2 and VEGFR2, respectively, may provide clinical benefit for some patients. Results of clinical studies show that Asian patients have increased survival compared to Caucasian patients. Differences between populations, and in particular the presence of polymorphisms capable of influencing the availability of fluorouracil, have been suggested as possible explanations. Other factors including histology, surgical procedures, administration of neoadjuvant chemotherapy in Western countries and screening programs in Asia have also been suggested. However, none of these elements can fully explain this phenomenon. The aim of this article is to present the main protocols used in clinical practice, the perspectives of metastatic gastric cancer treatment and the particularities observed in Asian and Caucasian patients.