PD-1 inhibitors Highly Effective for Colorectal Cancer in Lynch Syndrome Patients

This study, “Efficacy of PD-1 Inhibitors for Colorectal Cancer (CRC) and Polyps in Lynch Syndrome (LS) Patients”, was led by Yu et al. and colleagues.

It is already known that PD-1 inhibitors are effective for CRC with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). The main aim of the present study was to explore its effects on CRCs and colonic polyps in LS patients. In this study, researchers included LS patients with CRC who received at least two cycles of PD-1 inhibitors.

PD-1 inhibitors were given as a monotherapy or combined with other therapies like anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) treatment, radiotherapy, chemotherapy, and targeted therapy.

The key results of the study are:

• There were a total of 75 patients with a history of LS. The median age of these patients was 39 years.
• The patients were followed up for 27 months.
• The objective response rate (ORR) was 70.7%.
• The percentage of complete and partial responses was 28.0% and 42.7%.
• Four of five cases had proficient MMR (pMMR) or microsatellite stable (MSS) that were not responsive.
• Mucinous/signet-ring cell differentiation was associated with a lower ORR.
• The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively.
• During surveillance, 26 patients had Polyps.
• Seven adenomas which were larger than 7mm disappeared after treatment.

In this study, researchers highlighted the effectiveness of PD-1 inhibitors for LS dMMR/MSI-H CRC. They believe MSI and MMR status is crucial to tumour response to PD-1 inhibitors. They also mentioned less sensitivity of Mucinous and signet-ring cell LS CRC to PD-1 inhibitors.

Large adenomas of size ≥7mm in LS patients may respond to PD-1 inhibitors.

For  further reference log on to:

https://www.ejcancer.com/article/S0959-8049(23)00355-6/fulltext