Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry
by
, , , , , and
Luca G. Campana
1,*,†
,
Barbara Peric
2,3,†, 
Matteo Mascherini
4,
Romina Spina
5,
Christian Kunte
6,7,
Erika Kis
8,
Petra Rozsa
8,
Pietro Quaglino
9, 
Rowan Pritchard Jones
10,
A. James P. Clover
11,
Pietro Curatolo
12,
Roberto Giorgione
13,
Maja Cemazar
14,15,
Francesca de Terlizzi
16,
Masa Bosnjak
14,17 and
Gregor Sersa
14,18,*
1
Department of Surgery, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
2
Department of Surgical Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
3
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
4
Clinica Chirurgica 1, Ospedale Policlinico San Martino, University of Genova, 16100 Genova, Italy
5
Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua Veneto Institute of Oncology, 35121 Padova, Italy
6
Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, 80539 Munich, Germany
7
Department of Dermatologic Surgery and Dermatology, Artemed Fachklinik Munich, 81379 Munich, Germany
8
Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary
9
Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, 10124 Torino, Italy
10
Plastic Reconstructive Surgery, University of Liverpool, St. Helens & Knowsley Teaching Hospitals NHS Trust, Liverpool L35 5DR, UK
11
Plastic Reconstructive Surgery, Cork University Hospital and South Infirmary Victoria University Hospital and Plastic Surgery University College Cork, T12 DC4A Cork, Ireland
12
Policlinico Umberto I, University La Sapienza, 00185 Roma, Italy
13
Dermatologic Clinic of University of Eastern Piedmont, 28100 Novara, Italy
14
Department of Experimental Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
15
Faculty of Health Sciences, University of Primorska, 6310 Izola, Slovenia
16
IGEA S.p.A., Clinical Biophysics Laboratory Carpi, 41012 Modena, Italy
17
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia
18
Faculty of Health Sciences, University of Ljubljana, 1000 Ljubljana, Slovenia
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2021, 13(17), 4289; https://doi.org/10.3390/cancers13174289
Submission received: 6 July 2021
/
Revised: 14 August 2021
/
Accepted: 19 August 2021
/
Published: 25 August 2021
Simple Summary
Electrochemotherapy (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.
Abstract
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.
