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.
ABSTRACT
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.