Innovative Combination Therapy Shows Promise in Extending Survival for Patients with Advanced Skin Cancer

A recent phase 2 clinical trial has demonstrated that combining the immunotherapy drug avelumab with the targeted agent cetuximab significantly prolongs progression-free survival in patients suffering from advanced cutaneous squamous cell carcinoma (cSCC), a common and often aggressive form of skin cancer. The study, presented at the American Society of Clinical Oncology (ASCO) meeting and published in the Journal of Clinical Oncology, found that patients receiving the combination therapy experienced nearly four times longer median progression-free survival—11 months compared to 3 months in those treated with avelumab alone.

This trial, led by Dr. Dan Zandberg from the University of Pittsburgh, involved 57 participants with unresectable or metastatic cSCC. Patients were randomized to receive either a combination of avelumab, an immune checkpoint inhibitor targeting PD-L1, with cetuximab, which targets the epidermal growth factor receptor (EGFR), or avelumab alone. Notably, nine patients initially on avelumab switched to the combination after disease progression, highlighting the potential benefits of continued immunotherapy alongside targeted treatments.

The rationale for this combination stems from their complementary mechanisms: avelumab releases the brakes on the immune system by blocking PD-L1, allowing T cells to attack tumors, while cetuximab stimulates natural killer cells and dendritic cells, further boosting anti-tumor responses. The synergistic effect observed suggests these drugs work better together than separately.

While the trial showed promising results, the researchers note that current standard treatments such as cemiplimab and pembrolizumab—already approved for cSCC—have shown higher efficacy. Therefore, the combination may not become a first-line therapy but provides valuable insights into future therapeutic strategies. The findings support ongoing investigations into combining immunotherapy with other targeted agents to improve outcomes in advanced skin cancers.

Dr. Zandberg emphasized the importance of clinical trials in discovering new treatment avenues, stating, "Our goal is to develop options that can ultimately become part of the standard of care for patients with advanced cSCC." The trial's results offer a promising direction for enhancing immunotherapy efficacy and highlight the potential for combination approaches in managing difficult-to-treat skin cancers.

This pioneering study marks the first randomized trial comparing cetuximab plus PD-1/PD-L1 blockade versus PD-1/PD-L1 blockade alone in cSCC and head and neck cancers, paving the way for further research aimed at optimizing treatment combinations for better patient survival.