Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry.

Luca G Campana,Francesca De Terlizzi,Erika Kis,A James P Clover,Petra Rozsa,Matteo Mascherini,Romina Spina,Gregor Sersa,Pietro Curatolo,Barbara Peric,Rowan Pritchard Jones,Masa Bosnjak,Maja Cemazar,Christian Kunte,Pietro Quaglino,Roberto Giorgione

doi:10.3390/cancers13174289

Abstract

Simple SummaryElectrochemotherapy (ECT) combines a cytotoxic agent with locally applied electric pulses to enhance its antitumor effect. Over the last 15 years, ECT has been safely applied to patients with skin metastases in combination with other oncologic treatments and, more recently, with systemic immunotherapy. In this study, we aimed to investigate the effectiveness of ECT in combination with pembrolizumab. We compared patient outcomes after the following treatments: (a) pembrolizumab, (b) pembrolizumab and ECT, and (c) ECT alone. The combined application of pembrolizumab and ECT was safe and more efficacious in preventing further growth of cutaneous metastases than pembrolizumab alone. The patients treated with pembrolizumab and ECT experienced lower disease progression rates and longer survival than those who received pembrolizumab. ECT may boost the effect of pembrolizumab by acting as an in situ vaccination against cancer cells. Further studies are required to confirm these findings.Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC–IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.

Highlights

Recent advances in the treatment of metastatic melanoma have been achieved with the introduction of BRAF and MEK inhibitors, followed by immunotherapy with immune checkpoint inhibitors (ICIs)
The data of the pembrolizumab–ECT and ECT groups were retrieved from the International Network for sharing practices of ECT (InspECT) database, while those of the pembrolizumab cohort were collected from the Clinical Registry of Skin Melanoma (CRRS)
Skin-directed treatment with ECT in melanoma patients treated with pembrolizumab proved to be a safe and effective therapy to improve tumor response and local control on cutaneous metastases

Summary

Introduction

Recent advances in the treatment of metastatic melanoma have been achieved with the introduction of BRAF and MEK inhibitors, followed by immunotherapy with immune checkpoint inhibitors (ICIs). Humanized monoclonal antibodies such as anti-CLA-4 (ipilimumab) and anti-PD1 (pembrolizumab and nivolumab) release the inhibitory brake on T cells, unleashing the body’s immune response against cancer [1,2]. A recent analysis of 583 melanoma patients treated with pembrolizumab as part of the KEYNOTE-001 study identified LDH, site of metastases, and no prior therapy as the predictor of response, whereas LDH, low tumor burden, site of metastases, and ECO-PS were identified as predictors of OS [5]. Systemic immunotherapy and, in BRAF V600E/K-mutated melanoma, targeted therapy have been introduced with appreciable results [12]

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