Dr Patel on the Evolving Use of Neoadjuvant PD-1 Inhibitors in CSCC

Vishal Patel, MD, FAAD, FACMS, associate professor, Dermatology, George Washington (GW) School of Medicine & Health Sciences; director, Cutaneous Oncology Program, GW Cancer Center, discusses the evolving use of PD-1 inhibitors for patients with cutaneous squamous cell carcinoma (CSCC) in the neoadjuvant and adjuvant setting.

The use of PD-1 inhibition for patients with non-melanoma skin cancers such as CSCC has evolved significantly, taking cues from successful strategies in melanoma, Patel begins. These data have shown that patients with certain risk factors achieve better responses when treated with anti–PD-1 therapy earlier on in the disease course, he states. Initially, PD-1 therapy was used in cases of advanced, unresectable, metastatic disease. However, recent trials have explored the efficacy of this approach in earlier stages of disease, such as lymph node disease that is surgically resectable or primary tumors without distant metastases or lymph node metastases, Patel explains.

Trials evaluating PD-1 inhibitors in CSCC such as cemiplimab (Libtayo) alone or in combinations in the neoadjuvant space have demonstrated robust response rates and complete tumor responses, Patel reports. Although surgery remains integral to management strategies in this space, the efficacy of neoadjuvant PD-1 inhibition is changing the landscape by potentially reducing the extent of treatment needed for long-term cures after initial systemic immunotherapy followed by surgery. These outcomes have been observed across the spectrum of melanoma and non-melanoma skin cancers, and clinical trials are planned to expand these approaches into the basal cell carcinoma space, Patel says.

In comparison, the role of adjuvant immunotherapy for the treatment of CSCC remains largely uncharted, Patel continues. Traditionally, the gold standard for CSCC treatment has been surgery followed by adjuvant radiation therapy in cases of unclear margins, high-risk features, or concerns about potential systemic spread in the future. Ongoing immunotherapy trials are investigating whether adding immunotherapy after surgery and radiation can further benefit patients in the adjuvant space, Patel says.

He adds that several treatment regimens could be utilized not necessarily in the adjuvant setting, but for patients experiencing recurrence following surgery and radiation who may not qualify for systemic immunotherapy; for patients previously exposed to anti-EGFR medications or more classic chemotherapies; and to those who received radiation in a palliative setting. Completion of these ongoing trials is anticipated to provide clarity on the effectiveness and optimal use of adjuvant immunotherapy for preventing recurrence and improving outcomes in CSCC, Patel emphasizes.

The evolving treatment landscape underscores the importance of translational research from melanoma to non-melanoma skin cancers, potentially offering new avenues for personalized therapies and improving long-term outcomes for patients with CSCC. As these trials progress and data accumulates, clinicians remain hopeful for a clearer understanding of optimal adjuvant treatment strategies in CSCC, Patel concludes.