CARSKIN: Pembrolizumab as first line therapy in patients with unresectable cutaneous squamous cell carcinoma (cSCC).

Abstract

TPS9596 Background: Treatment options are limited for patients (pts) with locally advanced or metastatic cSCCs. Cisplatin-based combinations have some efficacy but their toxicity often prohibits their use, particularly for the elderly. New therapeutic options are needed. Tumors divert the programmed death receptor 1 (PD-1) pathway suppressing immune control. Pembrolizumab (MK-3475) is a high-affinity humanized monoclonal anti-PD-1 antibody. It leads to dual PD-1 ligand (PD-L1 and PD-L2) blockade that may reactivate the immune surveillance and elicit anti-tumor response. It has antitumor activity in several tumors including head and neck SCCs. Moreover, an efficacy of pembrolizumab in cSCCs has been reported recently in a series of 6 cases. Methods: CARSKIN (ClinicalTrials.gov, NCT02883556) is a French multicenter, open-label, nonrandomized phase 2 trial, designed to evaluate the efficacy and safety of pembrolizumab in 39 pts with unresectable and/or metastatic cSCCs, naive of chemotherapy and of EGFR inhibitors. Pembrolizumab is administered (200 mg IV Q3W) for up to 24 months or until disease progression or unacceptable toxicity. Eligible pts must undergo a baseline biopsy of the tumor prior to treatment for PD-L1 evaluation. Response is to be assessed at baseline, wk 9, 15 and 24, and thereafter Q12W by central radiology review per RECIST 1.1 and per modified RECIST v1.1. The primary objective is response rate (RR) at wk 15 per RECIST 1.1. Secondary efficacy objectives are to assess whether patients with PD-L1+ tumors have a better RR than the whole sample at wk 15 and to assess in the whole sample and in PD-L1+ pts, disease control rate (DCR) at wk15, RR at wk 24, best RR, overall survival (OS), progression free survival (PFS), duration of response / control and time to disease progression. A Simon optimal two-stage design will be used. Four responders among 19 pts will be needed in the 1st step to continue the trial. Overall 9 responses will be needed to conclude the effectiveness. Kaplan-Meier statistics will assess PFS and OS. Adverse events (AEs) will be assessed throughout the study and for 30 d thereafter (6 m for serious AEs) and graded per NCI CTCAE v4.0. Clinical trial information: NCT02883556.

Complete Resolution of a Large, Locally-advanced Cutaneous Squamous Cell Carcinoma with the Immune-modulating PD-1 Inhibitor Pembrolizumab

“…This case report highlights the occasional dramatic effect of PD-1 inhibition for the treatment of cSCC and it remains to be determined if this medication could outperforms cemiplimab in regard to efficacy or safety. Unpublished reports from a small (N=39) phase II clinical trial (CARSKIN, NCT02883556) study evaluating pembrolizumab as first-line monotherapy for unresectable cSCCs demonstrated robust antitumor activity regardless of PD-L1 expression levels and suggests similarly high efficacy compared to cemiplimab [16]. The lack of randomized, head-to-head comparisons of cemiplimab and pembrolizumab limit the ability to comment on the individualized risk:benefit anaylsis and approach to locally advanced or metastatic cSCC.…”

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death‐1 inhibitors: A review of the literature

“…Recommended doses are 3 mg for kilograms of weight every 3 weeks as intravenous (iv) infusion for a period of 30 minutes. Among the different PD-1 inhibitors, the number of patients treated is the widest, about 28 reported in the literature (Assam et al, 2016;Borradori et al, 2016;Chang et al, 2016;Degache et al, 2018;Deinlein et al, 2017;Ferrarotto, 2017;Lipson et al, 2016;Ravulapati et al, 2017;Stevenson et al, 2017;Tran et al, 2017;Winkler et al, 2017;Zalaudek et al, 2019), excluding the ongoing trials in Phase I and II (Licitra et al, 2017;Kudchadkar et al, 2018;Maubec et al, 2019). Although the larger number of reported cases, responses data are not enough and in addition with short period of follow-up.…”

“…Nowadays, the widest open trial is KEYNOTE‐629, a Phase II study enrolling 120 patients with Stage III and IV disease (Licitra et al, ) (LE 1b following Oxford CEBM Levels of Evidence). Maubec et al () reported partial results of the Stage I trial (CASKIN), including 19 patients (LE 1b following Oxford CEBM Levels of Evidence). Response rate (RR) of 42% at 15 weeks, corresponding to seven partial response (PR) and one complete response (CR) and only one responder progressed.…”

Update on the anti‐programmed cell death‐1 receptor antibodies in advanced cutaneous squamous‐cell carcinoma

“…At the 2019 ASCO meeting, a French trial using pembrolizumab in the same schedule (NCT02883556) in unresectable cSCC with no prior systemic therapy was also reported 3 . Of 39 patients by 15 weeks, there were 2 complete and 13 partial responses for an ORR of 38.5%.…”