Top Line: Immunotherapy produces relatively high pathologic complete response rates for patients with cutaneous squamous cell carcinoma.
The Study: This small, phase 2 trial sought to determine if surgery and adjuvant radiation could be de-escalated among patients with cSCC. The trial included 27 patients with locoregionally advanced, but resectable stage III (33%) or stage IV (67%) disease including 59% with node positive disease. Most of these tumors were in the head and neck region. They received neoadjuvant pembrolizumab every 3 weeks for 4 cycles. They also had FDG-PET at baseline, 6 weeks, and 12 weeks. Those with a complete metabolic response on PET underwent mapping biopsies of the primary site and nodes. If these were negative, they were considered to have a complete clinical response (48%), and they had no further surgery or radiation. Even though a complete response was enough to omit any further standard, curative therapy, it wasn’t enough to skip out on the obligatory 13 extra cycles of pembrolizumab. Those with less than a cCR went on to surgery, and those with a pCR (15%) skipped adjuvant RT while those with >10% viable tumor cells (37%) received adjuvant RT. At 18 months, the rate of EFS was 74%. No patients with a cCR or pCR had recurrence. Among those with a cCR or pCR, the rate of EFS at 12 months was 94% compared to just 40% in those without a cCR/pCR. If we’re bold enough to omit standard of care therapy based on systemic therapy response, perhaps we should also be bold enough to try omitting months of extremely costly experimental therapy with questionable incremental benefit.
TBL: In this small, phase 2 study, over half of patients with locoregionally advanced cSCC had a complete clinical response or pathologic response to neoadjuvant pembrolizumab and none had recurrence over a 12 month period without surgery or RT while on maintenance immunotherapy. | Ladwa, J Clin Oncol 2025
The Study: This small, phase 2 trial sought to determine if surgery and adjuvant radiation could be de-escalated among patients with cSCC. The trial included 27 patients with locoregionally advanced, but resectable stage III (33%) or stage IV (67%) disease including 59% with node positive disease. Most of these tumors were in the head and neck region. They received neoadjuvant pembrolizumab every 3 weeks for 4 cycles. They also had FDG-PET at baseline, 6 weeks, and 12 weeks. Those with a complete metabolic response on PET underwent mapping biopsies of the primary site and nodes. If these were negative, they were considered to have a complete clinical response (48%), and they had no further surgery or radiation. Even though a complete response was enough to omit any further standard, curative therapy, it wasn’t enough to skip out on the obligatory 13 extra cycles of pembrolizumab. Those with less than a cCR went on to surgery, and those with a pCR (15%) skipped adjuvant RT while those with >10% viable tumor cells (37%) received adjuvant RT. At 18 months, the rate of EFS was 74%. No patients with a cCR or pCR had recurrence. Among those with a cCR or pCR, the rate of EFS at 12 months was 94% compared to just 40% in those without a cCR/pCR. If we’re bold enough to omit standard of care therapy based on systemic therapy response, perhaps we should also be bold enough to try omitting months of extremely costly experimental therapy with questionable incremental benefit.
TBL: In this small, phase 2 study, over half of patients with locoregionally advanced cSCC had a complete clinical response or pathologic response to neoadjuvant pembrolizumab and none had recurrence over a 12 month period without surgery or RT while on maintenance immunotherapy. | Ladwa, J Clin Oncol 2025