Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma

Highlights

• In a real-life setting of cutaneous squamous cell carcinoma (cSCC), cemiplimab confirmed safety and effectiveness.

• Low performance status (PS), previous steroids/antibiotics and low haemoglobin reduce cemiplimab activity.

• Cemiplimab is feasible in patients with autoimmune or lymphoproliferative diseases.

Abstract

Background

Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy.

Methods

This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response.

Results

131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3–4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response.

Conclusions

Our real-world study showed safety and effectiveness results comparable to those obtained in clinical trials. We identified some clinical and biochemical factors potentially associated with response to cemiplimab.

Introduction

Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin cancer affecting predominantly elderly people in chronically sun-exposed areas, with increasing worldwide incidence [[1], [2], [3]]. The post-surgery disease-free survival rate at 5 years exceed 90%; however, less than 5% of the patients develop disease recurrence or progression, mainly within 2 years of the radical resection. The term advanced cSCC is currently used to define locally advanced cSCC, which by definition is no longer amenable to surgery or radiation therapy, and metastatic cSCC [4]. Although the overall disease specific survival of cSCC is favourable (93.6% at 10 years) [5], patients with advanced disease have poor long-term outcomes. Data from a French collaborative study [6] showed that median progression-free survival (PFS) and overall survival (OS) of patients with advanced cSCC after the first line of systemic treatment in the pre-check point inhibitors era was 6 months and 18.3 months, respectively.

Cemiplimab (REGN2810) is a programmed death protein-1 (PD-1) inhibitor approved in 2018 by both the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) for patients with locally advanced or metastatic disease who are not candidates for curative surgery or radiation therapy. The approval was based on the results of combined data from the phase I study, the pivotal phase II and a third study enrolling patients with advanced/metastatic cSCC, for a total of about 200 patients [[7], [8], [9]]. With a follow up of 43 months, the latest update reported an objective response rate (ORR) of 47.1%, with 17.1% complete responses and 72.5% clinical benefit. The median time to response was 2.1 months [10].

Despite the evidence reported by clinical trials, only a few data about cemiplimab activity and management in real-life are available [7,8]. Several questions still need to be addressed, such as tolerability and efficacy in a broader population, including patients usually excluded from clinical trials. From that perspective, patients with chronic immune depression (e.g. transplant recipients), patients with concomitant malignancies and those receiving high dose corticosteroids, are of particular interest. Moreover, additional data about potential clinical-pathologic determinants of clinical benefit in clinical practice are yet to be defined.

Against this background, we analysed clinical outcomes of patients with advanced cSCC enrolled within the named patient programme - compassionate use of cemiplimab in Italy.