Professor Danny Rischin
The longest reported follow-up of patients with advanced advanced cutaneous squamous cell carcinoma (CSCC) treated with an immune checkpoint inhibitor has confirmed the durability of responses to cemiplimab in Australian patients.
The findings, published in the Journal of the American Academy of Dermatology [link here], support other evidence for the use of PD-1 inhibitors as standard of care in advanced CSCC.
Of Australian patients recruited to the international EMPOWER-CSCC-1 trial, 54 patients with locally advanced or metastatic disease, who received either weight-based or fixed cemiplimab dosing for a median duration of 19 months, had a median follow-up of 77 months from start of treatment.
The median age of patients was 71 years, 91% were male, and the most common primary site of the CSCC was the head and neck region (70%).
The ORR for all patients was 72% of which 22% had a complete response and 50% had a partial response. A further 7% had stable disease and 20% had progressive disease.
The study found the median DoR and median OS were not reached in the responders and the 5-year estimate of patients remaining in response was 65%.
Median PFS was 56.4 months with an estimated 5 year PFS rate of 48% and the estimated 5-year OS rate was 60%.
“Among the 39 patients who had an initial response to cemiplimab, 10 progressed (best response CR for 2/10 and PR for 8/10). Eight of these progression events occurred within 3 years from commencing treatment,” the study said.
Four patients received a second course of cemiplimab for progressive disease subsequent to the initial treatment on trial .
Of the retreated patients with progression at the original site, one had a CR then subsequently progressed while two achieved stable disease and remained progression-free at data cutoff (7 and 46 months after initiation of re-treatment).
The fourth patient with progression at a new site had a CR to a second course of cemiplimab and remained progression-free at data cut-off, 46 months after initiation of re-treatment.
The investigators, including Professor Danny Rischin from the Peter MacCallum Cancer Centre, said the successful re-treatment with cemiplimab for patients who progressed after fixed-duration therapy had not previously been described in CSCC but was well described in advanced melanoma.
“The knowledge that patients may respond again to PD-1 inhibitors if they progress after cessation of treatment is important, given that there are currently no approved second-line therapies for patients with CSCC,” they said.
“Approaches harnessing a combination of immune checkpoint blockade and cetuximab, personalised vaccines and intralesional therapy such as toll-like receptor agonists, interleukins, oncolytic viruses are being investigated in the setting of PD-1 inhibitor refractory CSCC.”
Overall, despite the admittedly small and retrospective data collection, they said they had described long-term outcomes of patients beyond protocol defined follow-up in which the median DoR and median OS had not been reached.
“This represents the longest follow-up for patients with advanced CSCC treated with a PD-1 inhibitor (median 77 months) and demonstrates durability of responses to cemiplimab,” they said.
“In contrast to the historically dismal survival outcomes prior to the advent of ICIs, we demonstrate many patients with advanced CSCC treated with cemiplimab are long-term survivors.”