cetuximab (Lupitux / Cetuxa / ENZ124)

A Pilot Clinical Trial of Cetuximab Combined With Tislelizumab as Neoadjuvant Therapy for Locally Advanced Oral Squamous Cell Carcinoma.

Wu Wen-Jie WJ, An Pu-Gen PG, Hu Xiao X, Zhang Jian-Yun JY et al.

Chemotherapy-free neoadjuvant strategies remain undefined for patients with locally advanced oral squamous cell carcinoma (OSCC) who are medically unsuitable for conventional cytotoxic chemotherapy. In this prospective single-arm pilot trial, 15 patients received two cycles of neoadjuvant tislelizumab plus cetuximab before planned surgery. The primary endpoint was major pathological response (MPR). All patients completed neoadjuvant treatment and underwent radiographic assessment. The objective response rate was 73.3%. Twelve patients underwent surgery; five achieved MPR and two achieved pathological complete response. At a median follow-up of 23 months, the 2-year event-free survival and overall survival rates were 66.0% and 78.3%, respectively. No treatment-related deaths occurred. Neoadjuvant cetuximab plus tislelizumab showed feasible delivery, encouraging antitumor activity, and acceptable safety in patients with locally advanced OSCC who were medically unsuitable for conventional cytotoxic chemotherapy.

Second-line raltitrexed plus irinotecan (SALIRI) with bevacizumab, cetuximab, or alone for metastatic colorectal cancer: a prospective multicenter cohort-based secondary analysis of the SALLY trial.

Kou Furong F, Wang Xicheng X, Li Jian J, Wang Zhenghang Z et al.

The prospective multicenter SALLY registry reported that raltitrexed plus irinotecan (SALIRI)-based regimens can be used as second-line treatment for metastatic colorectal cancer (mCRC). Outcomes according to the addition of bevacizumab (Bev), cetuximab (Cet), or no targeted agents are less clear in routine practice. We performed an exploratory secondary analysis of the SALLY registry. We included patients who received second-line SALIRI + Bev, SALIRI + Cet, or SALIRI alone from the SALLY full analytical set. Treatment was selected by physicians in routine care; patients were not randomized. Tumor response, progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events were compared descriptively and with unadjusted statistical tests. Baseline clinicopathologic and molecular characteristics were assessed across groups. The analysis included 1,049 patients: 678 received SALIRI + Bev, 103 received SALIRI + Cet, and 268 received SALIRI alone. Groups were broadly similar in sex, Eastern Cooperative Oncology Group (ECOG) performance status, pathological type, resection status, and metastatic burden, but differed in age, primary tumor location, and molecular profile among tested patients. The SALIRI + Cet group included more patients with left-sided or rectal tumors and RAS wild-type disease. BRAF-mutant tumors were found only in the SALIRI + Bev and SALIRI-alone groups. Compared with SALIRI alone, SALIRI + Cet was associated with a higher objective response rate (ORR) (27.2% vs. 15.7%; P=0.02) and longer OS (19.9 vs. 17.0 months; P=0.006). SALIRI + Bev showed numerically higher ORR, DCR, and PFS than SALIRI alone, but these differences were not statistically significant. SALIRI + Cet and SALIRI + Bev did not differ significantly in ORR, DCR, PFS, or OS. Grade 3-4 treatment-related adverse events were infrequent and generally similar across groups, although rash was more common with SALIRI + Cet. In this exploratory, nonrandomized secondary analysis of a prospective multicenter registry, SALIRI combined with Bev or Cet was feasible and tolerable as second-line therapy for mCRC. The observed favorable outcomes in the SALIRI + Cet subgroup should be interpreted cautiously because of nonrandom treatment allocation. Future prospective, biomarker-driven and randomized studies are warranted to define the optimal clinical positioning of SALIRI-based combinations.

Cetuximab-loaded self-assembled polymeric nanoparticles for the integrin-targeted therapy of glioblastoma.

Mishra Dhiraj D, Calderón Marcelo M, Beloqui Ana A, Sosnik Alejandro A

The blood-brain barrier (BBB) restricts the delivery of therapeutic small-molecule and macromolecular drugs to the central nervous system and precludes the therapeutic application of monoclonal antibodies in glioblastoma (GBM). In this work, we investigate integrin-targeted polyelectrolyte complex nanoparticles for the delivery of the anti-epidermal growth factor receptor monoclonal antibody cetuximab (CET) across the BBB in GBM. For this, an amphiphilic chitosan-graft-poly(methyl methacrylate-co-acrylic acid) copolymer is functionalized with cyclo(Arg-Gly-Asp-D-Phe-Val) (PEP) to engage ανβ3 and ανβ5 integrins expressed by the BBB endothelium and overexpressed by the GBM cells and co-assembled with sodium alginate using a T-junction microfluidics device. This double self-assembly method results in optimal CET encapsulation efficiency (∼99%) and the formation of loaded nanoparticles with a diameter of ∼322 nm, with very good structural fidelity and ∼16% w/w payload. Nanoparticles show very good compatibility with the human brain microvascular endothelium cell line hCMEC/D3 and the GBM cell line U87. Moreover, PEP-conjugated nanoparticles display significantly greater apparent permeability (Papp) in hCMEC/D3 monolayers grown on semi-permeable membranes, an in vitro model of the BBB, than the unmodified counterparts; Papp values being consistent with macromolecular systems capable of achieving measurable BBB transport in vivo. Cell uptake studies in both cell types using confocal laser scanning microscopy and imaging flow cytometry reveal an energy-dependent internalization pathway and a significant increase of the targeted nanoparticles with respect to the unmodified ones. Finally, CET-loaded nanoparticles significantly reduce the viability of the U87 cells, a model of GBM in vitro, suggesting its very good antitumoral activity in vitro. Overall results support the potential of these doubly self-assembled polymeric nanoparticles for the encapsulation and targeted delivery of therapeutic macromolecules to the brain.

Eruptive Melanocytic Nevi Associated With Encorafenib and Cetuximab Therapy in Two Patients With BRAF V600E-Mutated Colorectal Cancer.

Shuto Takayuki T, Nakajima Michiko M, Okada Etsuko E