A phase II clinical trial led by the alliance for clinical trials in oncology has respected its main evaluation criterion, demonstrating that the combination of the Oulumab and the ketximab has improved progression survival (PFS) compared to Oulumab alone in patients with advanced cutaneous epidermoid carcinoma (CSCC). The results, presented as an oral summary at the annual meeting of the American Society of Clinical Oncology (ASCO), and published in the Journal of Clinical OncologySuggest a new promising approach for patients with this aggressive form of skin cancer.
These results show that the combination of the inhibition of the immune control point targeting the PD-1 path: PD-L1 with a VELUMAB plus a monoclonal ceremonial targeted by the EGFR can offer a significant clinical advantage compared to the EVELAMAB alone for patients with advanced CSCC. He opens the door to future research and new strategies to improve results in this difficult disease. “”
Dan Zandberg, MD, principal researcher and director of head and neck and thyroid cancer disease at UPMC Hillman Cancer Center
Cutaneous epidermoid carcinoma is one of the most common cancers in the United States, with around 700,000 to 1 million new cases diagnosed each year. Although most cases are treated, more than 12,500 cases increased towards nodal or distant metastases each year, contributing to around 2,000 to 8,000 deaths per year.
Approved immune point -point inhibitors, CEMIPLIMAB and PEMBROLIZUMAB have advanced the treatment landscape, but many patients are still experiencing the progression of the disease. Preclinical research suggests that the combination of blocking of the PD-1 route: PD-L1 plus an IgG1 monoclonal antibody like Cetuximab, which targets EGFR and activates innate immunity via cell cytotoxicity dependent on antibodies (ADCC), can create a synergistic effect.
The test (alliance A091802) was designed to assess whether this double mechanism could improve the PFS. Patients were randomized in one of the two groups: Oulumab monotherapy every two weeks or the combination of Oulumab Plus Cetuximab, also administered every two weeks. Patients progressing on Oulumab alone have been authorized to move on to combined therapy, allowing an evaluation of efficiency in first -line refractory environments and immunotherapy.
From 2019 to 2023, the study scored 60 patients with advanced CSCC in the United States; 57 were assessable. The median age of participants was 72 years. The majority was white (96.5%) and male (91.2%), all patients were HIV-positive and 75.4%expressed PD-L1. Most tumors (84.2%) come from the head or neck region, and 47.1% of patients had distance metastases. The basic characteristics were balanced between treatment groups and randomization was stratified by PD-L1 status. The combination of Oulumab and Cetuximab has considerably improved the main evaluation criterion of the PFS compared to Oulumab alone. The median PFS was 11.1 months (95% confidence interval (CI): 7.6-not reached (NR)) in the Avelumab Plus Cetuximab group compared to 3.0 months (95% CI: 2.7-13.6) in the Avelumab group alone, with a risk ratio (HR) of 0.48 (95% CI: 0.23 to 0.0.97, P = 0.018).
Nine patients in the arm of monotherapy Envelumab crossed the Avelumab Plus Cetuximab group and the median PFS after crossing was 11.3 months (5.8-NR). The global median survival (OS) of the Avelumab group plus Cetuximab was not reached (25.2 – NR) compared to the Avelumab group which was 35.8 months (18.6 – NR) HR 0.78 (0.34‒1,80) p = 0.279 The rate of confirmed objective response (orr) was 27.6. group alone.
The side effects linked to treatment took place in 93% of patients who received the Oulumab plus Cetuximab; and in 78.6% of those who received the Oulumab. More serious side effects (grade 3 or more) were observed in 48.3% of patients receiving the Oulumab plus Cetuximab and in 21.5% of those who receive treatment at Oulumab. The most common serious side effects in the combination group were rastered rashes (20.7%) and reactions related to infusion (20.7%). There was no death related to unexpected treatment or toxicity.
Alliance A091802 is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded national clinical trials network (NCTN) as part of a collaboration with EMD Serono, a business of Merck KGaA, Darmstadt, Germany, who provided Avelumab et support d’essai. Pour en savoir plus sur l’étude, visitez ClinicalTrials.gov.
(Support by the National Cancer Institute of the National Institutes of Health under the reward numbers U10CA180821 and U10CA180882 (at the Alliance for Clinical Trials in Oncology); U24CA196171; U10CA180868 (NRG ONCOLOGY); U10CA18088 (SWOG) Bususk Darmstadt, Germany)
