Neoadjuvant Immune Checkpoint Inhibitor Therapy for Localized Deficient Mismatch Repair Colorectal Cancer

Abstract

ImportanceColorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) account for 15% of all CRCs. Deficient MMR is a predictive biomarker associated with responsiveness to immune checkpoint inhibitors (ICIs) in solid tumors, including CRC. The remarkable effectiveness of ICIs in metastatic CRC has led to their evaluation in the neoadjuvant and adjuvant treatment of localized disease.ObservationsMultiple prospective phase 2 studies in limited numbers of patients with localized dMMR CRC demonstrate high complete clinical and pathological response rates (60%-100%) to neoadjuvant ICIs, with low rates of grade 3 or higher ICI-related toxic effects. Given the median follow-up of 12 to 25 months in these studies, longer-term monitoring is needed to determine the durability of response and to ensure that oncologic outcomes are not compromised in patients undergoing nonoperative management. Neoadjuvant ICI therapy is especially attractive for patients with rectal cancer given the significant morbidity that accompanies pelvic irradiation and total mesorectal excision. Ongoing and planned prospective phase 2 trials will provide further data on important issues, including optimal neoadjuvant treatment duration, ICI monotherapy vs combination, and the need for adjuvant ICI therapy.Conclusions and RelevanceWhile this review found that early results of neoadjuvant immunotherapy for localized dMMR CRC show high rates of major and complete pathological response, longer-term follow-up data are needed to ensure that oncologic outcomes are not compromised and are ideally improved. Neoadjuvant ICI therapy in localized dMMR CRC represents a potential paradigm shift with implications for organ preservation.

Endoskopische Resektionsverfahren von flächigen Präkanzerosen und Frühkarzinomen im Rektum

“…Weitere Untersuchungen und Langzeitergebnisse bleiben abzuwarten. Die intermuskuläre Dissektion könnte auch in Hinblick auf neue Immuntherapien für ausgewählte Fälle an Rektumkarzinomen neue Perspektiven bieten und wird hier zu evaluieren sein 39 40 41 .…”

Targeting novel regulated cell death: Ferroptosis, pyroptosis and necroptosis in anti‐PD‐1/PD‐L1 cancer immunotherapy

“…The application of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has shown remarkable success in clinical settings. 1 , 2 Since their initial FDA approval in 2011, ICIs have rapidly become integral to various cancer treatment protocols. 3 This approval has revolutionised cancer care and paved the way for significant progress in ICIs and other immuno‐oncology therapies.…”