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In sufferers with a sophisticated sort of pores and skin most cancers referred to as cutaneous squamous cell carcinoma (cSCC), those that obtained the mixture of the immunotherapy drug avelumab and focused agent cetuximab had nearly 4 occasions longer median progression-free survival in comparison with sufferers who obtained avelumab alone, in keeping with the outcomes of a part 2 trial introduced as we speak on the American Society of Medical Oncology (ASCO) assembly and concurrently revealed within the Journal of Medical Oncology.
“It is both an honor and humbling to develop clinical trials that can be potential options for our patients,” stated lead writer and examine chair for the trial, Dan Zandberg, M.D., affiliate professor of drugs on the College of Pittsburgh and medical oncology co-leader of the pinnacle and neck most cancers program at UPMC Hillman Most cancers Heart. “My hope is that the insights we made with this trial will lead to additional studies that can ultimately bring a new immunotherapy-based combination into standard of care for patients with advanced cSCC.”
cSCC is a standard sort of pores and skin most cancers with about 1.8 million instances recognized within the U.S. annually. About 95% of cSCCs are detected early and could be handled with minor surgical procedure. However in uncommon instances, sufferers will go on to develop superior cSCC, which incorporates domestically superior tumors that can not be surgically eliminated and metastatic illness. At this level, the prognosis is poor and therapy is targeted on extending survival, not remedy.
Zandberg developed the Alliance A091802 (NCT03944941) part 2 trial in collaboration with the Alliance for Medical Trials in Oncology via the Nationwide Most cancers Institute’s (NCI) Nationwide Medical Trials Community.
This trial, which was open nationwide, included 57 sufferers with superior cSCC. UPMC Hillman was the main website for affected person recruitment, with a few of these sufferers recruited and handled at its community of greater than 70 group most cancers facilities.
Twenty-nine sufferers obtained avelumab and cetuximab and 28 obtained avelumab alone. As a result of the trial had a crossover design, 9 sufferers within the avelumab group whose most cancers progressed switched to the mixture group.
Avelumab is an immune checkpoint inhibitor drug that targets a protein discovered on most cancers cells referred to as PD-L1. When PD-L1 binds to a receptor on T cells referred to as PD-1, it acts like a brake, slowing down the cancer-killing exercise of T cells. Avelumab and different anti-PD-1/PD-L1 therapies launch these brakes.
Cetuximab is a monoclonal antibody that targets EGFR (epidermal development issue receptor), a protein that performs a vital function in tumor cell development, proliferation and survival and which is usually present in excessive ranges on cSCC cells. It prompts pure killer cells, which assist combat tumors, and can even activate dendritic cells, which might then stimulate T cells. Earlier analysis achieved at UPMC Hillman by Robert Ferris, M.D., Ph.D. and his lab helped reveal cetuximab’s impact on the immune system.
“The rationale for the combination is that avelumab and other anti-PD-1/PD-L1 therapies have been shown to take the foot off the brake of the immune system, while cetuximab is pressing on the gas pedal—trying to work together to make the immune system go faster and attack the tumor,” stated Zandberg. “What’s exciting is that in this trial the efficacy of the combination suggests that the two drugs were synergistic, rather than just additive.”
The examine confirmed that the first endpoint of progression-free survival was considerably greater in sufferers who obtained avelumab plus cetuximab with a median of 11 months in comparison with simply 3 months in sufferers who obtained avelumab alone.
Regardless that avelumab and cetuximab led to an nearly quadrupling of median progression-free survival in comparison with avelumab alone, the trial doesn’t help this mixture as a regular therapy for sufferers. That is as a result of for the reason that trial was launched, two different anti-PD-1/PD-L1 therapies—cemiplimab and pembrolizumab—have been accredited and had greater efficacy than avelumab in trials in sufferers with cSCC.
Nevertheless, the trial represents the primary accomplished potential randomized comparability of cetuximab plus blockade of the PD-1/PD-L1 pathway versus blockade of that pathway alone in cSCC or head and neck most cancers, the place this mixture has additionally proven promise. The trial gives beneficial info for future trials.
“These findings highlight the potential benefits of combining cetuximab with an anti-PD-1/PD-L1 therapy and points to the importance of additional clinical trials combining either standard of care pembrolizumab or cemiplimab with cetuximab as a potential way to improve patient outcomes in advanced cSCC,” stated Zandberg.
Notably, sufferers within the crossover arm had an analogous progression-free survival to those that obtained the mixture from the beginning. Presently, if a affected person fails immunotherapy with pembrolizumab or cemiplimab, they change to cetuximab or chemotherapy. However this trial means that persevering with immunotherapy and including cetuximab may very well be extra useful.
Extra info:
Dan P. Zandberg et al, Part II (Alliance A091802) Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Superior Cutaneous Squamous Cell Carcinoma, Journal of Medical Oncology (2025). DOI: 10.1200/JCO-25-00759
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Mixture remedy extends survival in superior pores and skin most cancers, trial finds (2025, June 1)
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