In an Australian phase II trial (De-Squamate) reported in the Journal of Clinical Oncology, Ladwa et al found that the use of pembrolizumab produced a high rate of clinical or pathologic complete response in patients with resectable cutaneous squamous cell cancer (cSCC), suggesting the potential to avoid surgery and radiotherapy in this setting.
Study Details
In the multicenter trial, 27 patients with resectable stage II to IV (M0) cSCC started treatment with pembrolizumab between June 2022 and July 2023. Patients received pembrolizumab at 200 mg every 3 weeks for four cycles and then underwent 18F-labeled fluorodeoxyglucose–positron-emission tomography. Those with a clinical complete response (cCR), defined as a complete metabolic response and negative mapping biopsies of target site(s), did not undergo planned surgery and adjuvant radiotherapy (total de-escalation). Those without cCR underwent surgery with omission of adjuvant radiotherapy (partial de-escalation) recommended in those with a pathologic complete response (pCR). Patients then received 13 cycles of maintenance pembrolizumab. The primary outcome measure was clinical or pathologic complete response (cpCR), reflecting the combined rate of cCR and pCR.
Key Findings
A total of 17 patients (63%, 95% confidence interval [CI] = 42%–80%) achieved cpCR, including cCR in 13 patients (48%) and pCR in 4 patients (15%). Total de-escalation of treatment was achieved in 48% of patients and partial de-escalation, in 15%.
At a median follow-up of 18 months, no recurrences were observed among the 17 patients with cpCR. Among all patients, the event-free survival rate at 18 months was 74%. For patients with cpCR, median event-free survival was not reached, with a 12-month rate of 94% (95% CI = 76%–99%). Among patients without cpCR, median event-free survival was 7 months (95% CI = 0–14.7 months), with a 12-month rate of 40% (95% CI = 15%–70%).
Among all patients, the most common treatment-related adverse events of any grade were fatigue (37%), pruritus (30%), and diarrhea (26%). Treatment-related grade ≥ 3 adverse events were observed in two patients (7%), consisting of acute kidney injury in both. Grade 3 immune-related adverse events occurred in two patients (primary adrenal insufficiency and myositis). No treatment-related deaths were reported.
The investigators concluded: “Pembrolizumab led to a high rate of cpCR in resectable cSCC and demonstrated the potential to avoid surgery and radiotherapy.”
Rahul Ladwa, MBChB, MPhil, of Princess Alexandra Hospital, Brisbane, Queensland, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp and Dohme Australia. For full disclosures of all study authors, visit ascopubs.org.
