Consideration of the efficacy and side effects of immunotherapy based combination therapy in individual oncology treatment

Harisi Revekka
Dél-pesti Centrumkórház–Országos Hematológiai és Infektológiai Intézet, Onkológiai Osztály, Budapest

The approval of the first immune-checkpoint inhibitors (ICIs) marked a paradigm shift in the treatment of malignancies. While single-agent ICIs were initially used, today an increasing number of patients are being treated with ICI-based combination therapy (immunotherapy, chemotherapy, targeted therapy, radiotherapy, surgery). Chemother apy has always been largely considered immunosuppressive, but accumulating preclinical and clinical evidence shows that certain chemotherapeutic drugs can stimulate anti-tumour immunity under certain conditions and successfully potentiate ICI-based therapy. Several studies have demonstrated the synergistic effect of combining ICIs with targeted therapy. We present the current state of the art of studies on targeted therapy-ICI combination, focusing on angiogenesis inhibitors, EGFR/HER2 inhibitors, PARP inhibitors and MAPK/ERK signaling pathway inhibitors. Several preclinical models suggest a synergy between radiotherapy and ICIs and this approach is now used in the clinic. The promising neoadjuvant role of ICIs will be specifically addressed. In our article, we present the rationale for ICI-based combination therapies and clinical data from clinical trials in the immuno-oncology spectrum. We discuss the potential new directions that comprehensive biomarker studies may lead to. The different types and possible mechanisms of adverse events associated with combination therapies will be analysed, and strategies and targets for prevention and therapeutic in terventions to mitigate them will be described. In our review, immunotherapy-based combination therapies arguably offer more clinical benefits, but may also increase the number of high grade adverse events. With early detection and appropriate treatment strategies, these side effects can be significantly reduced, contributing to long-term, high-quality patient survival.


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