Biomarker-guided precision immunotherapy in head and neck cancer: Harnessing toripalimab-tpzi as a PD-1 checkpoint inhibitor

Abstract

The recent humanized anti-programmed death-1 (PD-1) monoclonal antibody, toripalimab-tpzi, has now become a promising immunotherapeutic agent in the control of head and neck cancer (HNC), especially head and neck squamous cell carcinoma (HNSCC), the most common form of the disease, constituting approximately 90 % of all cases. In this conceptual review, the authors critically examine the molecular processes, clinical activity, safety, biomarker-guided precision of their approach, resistance biology, and combination regimens of toripalimab-tpzi in HNSCC. Toripalimab-tpzi offers antitumor effects due to selective inhibition restricting the PD-1/programmed death-ligand 1 (PD-L1) axis, which restores cytotoxic T-cell activity and intensifies the antitumor immune responses. In the Phase I-III clinical trials on recurrent or metastatic HNSCC, the objective response rates of toripalimab-tpzi were around 20-36, the median progression-free survival (PFS) was 2.8–4.5 months, and the median overall survival was 10–15 months, especially with PD-L1-enriched populations. The safety profile is comparable to the PD-1 class effects, and the majority of the immune-related adverse events (irAEs) were grade 1-2 and grade 3-4 toxicities that were rare in less than 20 percent of the patients. The new evidence is pointing to the significance of patient selection according to biomarker to maximize therapeutic response. The single predictive utility of such markers as PD-L1 expression, tumor mutational burden, microsatellite instability, tumor-infiltrating lymphocytes, or immune gene signatures is variable, with the deficiency of single-biomarker systems. Integration therapy involving toripalimab-tpzi and platinum-based chemotherapy, radiotherapy, targeted therapies, or other immunomodulators has been shown to result in better response rates (up to 4060 % in select studies) and may result in resistance being overcome by intrinsic or acquired immunomodulatory mechanisms. Unlike previous generalized scientific reviews of PD-1/PD-L1 blocking in HNSCC, the article summarizes the toripalimab-tpzi-specific clinical and translational data and suggests a precautionary immunotherapy paradigm and a biomarker-driven combination-resistance management plan. Taken together, the above data favor toripalimab-tpzi as a clinically significant supplement to precision immunotherapy in HNSCC, whose optimal role is determined by the biologically informed selection of patients and the rational combination of multimodal treatment.