It is rare in oncology medicine to witness results that make you cry out for a miracle. Yet that is exactly what happened with the Alliance A091802 study, just published in Journal of Clinical Oncology. We are talking about patients with advanced skin cancer who, thanks to a combination of two immunotherapy drugs, have seen their progression-free survival increase almost fourfold.
From three months to eleven. A difference that, for those living with this type of aggressive tumor, represents the distance between despair and the concrete hope of recovery.
An enemy that seemed invincible
Il skin squamous cell carcinoma It is the second most common skin cancer after basal cell carcinoma, but certainly the most feared when it reaches advanced stages. Approximately 1,8 million new cases are diagnosed each year in the United States., and while the vast majority can be successfully treated when detected early, there is a particularly aggressive subgroup that develops metastases and resistance to conventional therapies.
Dan P. Zandberg, associate professor of medicine at theUniversity of Pittsburgh and director of the head, neck and thyroid cancer sections at theUPMC Hillman Cancer Center, led this potentially life-changing study. The study involved 57 patients with advanced cancer who were randomized to receive either avelumab immunotherapy alone or avelumab and cetuximab in combination.
How this dual strategy works in cancer
The idea behind the study is really brilliant: While avelumab takes the brake off the immune system, cetuximab steps on the accelerator. Avelumab belongs to the family of anti-PD-L1 immune checkpoint inhibitors, drugs that prevent tumor cells from “turning off” the immune response. On the other hand, cetuximab is a monoclonal antibody that targets the EGFR receptor, which is very present in carcinoma cells, and simultaneously activates the mechanisms of antibody-dependent cellular cytotoxicity.
The results exceeded all expectations: Median progression-free survival increased from 3,0 months with avelumab alone to 11,1 months with the combinationWe are talking about a hazard ratio of 0,48, which means a 52% reduction in the risk of progression or death with dual therapy.
Cancer and Patients: A Forgotten Population
The study enrolled patients with a median age of 72 years, mostly Caucasian men. 75,4% of participants expressed PD-L1, and the majority of tumors (84,2%) originated in the head and neck region. Nearly half of the patients (47,1%) already had distant metastases at enrollment.
What makes these results even more significant is that Patients with advanced skin cancer traditionally have a life expectancy of about one year. Before the advent of immunotherapy, there were no standard therapies for these cases., and physicians had to resort to off-label regimens with very limited evidence of efficacy.
A collaboration that makes the difference
The Alliance A091802 trial was made possible by a collaboration between the National Cancer Institute and EMD Serono, which provided avelumab and logistical support. This public-private partnership demonstrates how the evolution of immunotherapy is opening new horizons even for tumors that until recently were considered incurable.
But we mustn't rush too much.: the study used avelumab, while today's standard of care for advanced cancer includes cemiplimab and pembrolizumab, which have shown superior efficacy to avelumab in other trials. However, the principle of combining immunotherapy plus targeted therapy could also be applied to these newer drugs.
The Future of Skin Cancer
These results open up exciting scenarios for the future. As we have already seen with other forms of immunotherapy, the key to success often lies in the intelligent combination of different approaches that hit the tumor on multiple fronts simultaneously.
The road is still long, but for the first time in decades, when we talk about advanced skin cancer, the word “hope” no longer sounds like a pitiful euphemism, but like a tangible possibility based on hard scientific data.
