Pembrolizumab as first-line therapy in patients with unresectable cutaneous squamous cell carcinoma (cSCC): Phase 2 results from CARSKIN.

Abstract

9547 Background: Cemiplimab, a PD-1-axis blocking agent, has recently been approved for unresectable cSCCs. We report results of the CARSKIN study evaluating pembrolizumab in the first-line setting. Methods: Chemotherapy naive patients (pts) with unresectable cSCCs, either locally or regionally advanced or metastatic, and ECOG PS ≤1 were accrued to this multi-institutional phase II trial to assess tumor response rate (RR) and safety of pembrolizumab administered IV (200 mg Q3W) for a period up to 24 months (mo). Baseline PD-L1 expression was centrally assessed on tumor. The primary endpoint was the RR at 15 weeks (wks) per RECIST v1.1 (independent review). A Simon two-stage design was used. Results: From 03/2017 to 01/2018, 39 pts (79% males, median age 79 years) were enrolled. Disease was local (18%), regional (62%) or metastatic (21%); 38% of pts were PS 0. The median number of infusions was 8. The median follow-up was 10.2 mo; 15 pts are still on pembrolizumab. Thirty-four pts were evaluable for tumor response, and 39 for toxicity. The RR at 15 wks was 38.5 % (95% CI: 24–55%) in the ITT population corresponding to 2 CR and 13 PR. The best responses were 3 CR and 12 PR. The DCR was 51% (20/39 including 5 SD) at 15 wks. The median PFS was 8.4 mo and the median OS was not reached. No responder has progressed to date including 2 pts who discontinued pembrolizumab for 6 to 12 mo. Treatment-related AEs (TRAEs) occurred in 67% of pts, including 8% with severe TRAEs (1 gr 3 cholestasis, 1 gr 3 colitis and 1 death due to recurrence of a non-related head and neck cancer) and 10% who discontinued because of a TRAE. Centrally assessed baseline PD-L1 expression was positive in 77% of patients (1% tumor staining threshold), but it failed to predict response at 15 wks with a median PD-L1 expression of 10% in responders and non-responders at 15 wks (P = .55). Conclusions: In this series of 39 elderly pts with unresectable cSCCs, the safety profile was consistent with previous pembrolizumab studies. First-line pembrolizumab provided robust antitumor activity regardless of PD-L1 expression levels. Clinical trial information: NCT02883556.

Survival after parotid gland metastases of cutaneous squamous cell carcinoma of the head and neck

“…However, detailed guidelines for indication are still missing which might be-at least in part-due to a lack of appropriate clinical studies for patients with recurrent or metastasised CSCC [27]. Steeb et al reviewed the previous studies and experiences using checkpoint inhibitors in advanced CSCC and concluded that cemiplimab and pembrolizumab immunotherapy could result in a response rate of 40-55% in a first-line palliative setting [27][28][29]. These promising results might be due to a high immunogenicity of CSCC [30].…”

Dramatic response of refractory metastatic squamous cell carcinoma of the skin with cetuximab/pembrolizumab

“… 6 Similarly, pembrolizumab has achieved in a recent phase II study a 38.5% response rate, with excellent tolerability. 7 …”

Where do we stand with immune checkpoint blockade for advanced cutaneous squamous cell carcinoma? A systematic review and critical appraisal of the existing evidence

“…Four prospective phase II studies and one phase I study were identified. [3][4][5][6][7][8] The remaining records included one expanded-access programme, two retrospective analyses and 22 case reports or series. The number of patients per study ranged from one to 137.…”

“…Cemiplimab and pembrolizumab appear to be the most evidencebased substances in this setting, as they yielded response rates consistently from 40% to 55% and were investigated in methodological studies of higher quality. [3][4][5][6][7][8] We also contacted the authors of the included studies, who consistently confirmed the use of cemiplimab as the current standard of care for advanced cSCC. Other agents of ICB also showed promising clinical results with objective and durable responses.…”

“…1,2 Dupilumab was demonstrated to be an effective treatment for patients with moderate-to-severe atopic eczema in clinical trials. [3][4][5] Real-world evidence is now needed to evaluate its effectiveness and safety in routine care. Here we describe the first results of an interim analysis of the TREATgermany registry regarding the implementation of dupilumab as a new treatment option in routine care.…”