Durability of response to immune checkpoint inhibitors in metastatic Merkel cell carcinoma after treatment cessation

Alison M Weppler; Laetitia Da Meda; Ines Pires da Silva; Wen Xu; Giovanni Grignani; Alexander M Menzies; Matteo S Carlino; Georgina V Long; Serigne N Lo; Ina Nordman; Christopher B Steer; Megan Lyle; Claudia Trojaniello; Paolo A Ascierto; Celeste Lebbe; Shahneen Sandhu

doi:10.1016/j.ejca.2023.01.016

Durability of response to immune checkpoint inhibitors in metastatic Merkel cell carcinoma after treatment cessation

Eur J Cancer. 2023 Apr:183:109-118. doi: 10.1016/j.ejca.2023.01.016. Epub 2023 Jan 30.

Authors

Alison M Weppler¹, Laetitia Da Meda², Ines Pires da Silva³, Wen Xu⁴, Giovanni Grignani⁵, Alexander M Menzies⁶, Matteo S Carlino³, Georgina V Long⁷, Serigne N Lo⁷, Ina Nordman⁸, Christopher B Steer⁹, Megan Lyle¹⁰, Claudia Trojaniello¹¹, Paolo A Ascierto¹¹, Celeste Lebbe², Shahneen Sandhu¹²

Affiliations

¹ Peter MacCallum Cancer Centre, Melbourne, Australia.
² Institut du cancer AP-HP. Nord - Université Paris Cité Dermato-Oncology, Hôpital Saint Louis, Paris, France.
³ Melanoma Institute of Australia, The University of Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Australia; Westmead & Blacktown Hospital, Sydney, Australia.
⁴ Princess Alexandra Hospital, Brisbane, Australia; The University of Queensland, Brisbane, Australia.
⁵ Candiolo Cancer Institute, FPO - IRCCS, Candiolo (TO), Italy.
⁶ Melanoma Institute of Australia, The University of Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia.
⁷ Melanoma Institute of Australia, The University of Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Australia.
⁸ Calvary Mater Newcastle, Waratah, Australia; University of Newcastle, Newcastle, Australia.
⁹ Border Medical Oncology, Albury Wodonga Regional Cancer Centre, Albury, Australia Cairns Hospital, Cairns, Australia; University of NSW, Rural Clinical Campus, Albury, Australia.
¹⁰ Cairns Hospital, Cairns, Australia; James Cook University, Cairns, Australia.
¹¹ Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy.
¹² Peter MacCallum Cancer Centre, Melbourne, Australia. Electronic address: shahneen.sandhu@petermac.org.

PMID: 36842413
DOI: 10.1016/j.ejca.2023.01.016

Abstract

Background: Metastatic Merkel cell carcinoma (mMCC) is highly responsive to immune checkpoint inhibitors (ICIs); however, durability of response after treatment cessation and response to retreatment in the setting of progression is unknown.

Methods: Patients (pts) having mMCC from 10 centres who discontinued ICI treatment for a reason other than progression were studied.

Results: Forty patients were included. Median time on treatment was 13.5 months (range 1-35). Thirty-one patients (77.5%) stopped treatment electively while 9 patients (22.5%) stopped due to treatment-related toxicity. After median of 12.3 months from discontinuation, 14 pts (35%) have progressed (PD). Disease progression rate following ICI discontinuation was 26% (8 of 31) in patients who discontinued in complete response (CR), 57% (4 of 7) in patients in partial response and 100% (2 of 2) in those with stable disease. Median progression-free survival (PFS) after treatment cessation was 21 months (95% confidence interval [CI], 18- not reached [NR]), with a third of patients progressing during their first year off treatment. PFS was longer for patients who discontinued ICI electively (median PFS 29 months; 95% CI, 21-NR) compared to those who stopped due to toxicity (median PFS 11 months; 95% CI, 10-NR). ICI was restarted in 8 of 14 pts (57%) with PD, with response rate of 75% (4 CR, 2 partial response, 1 stable disease, 1 PD).

Conclusion: ICI responses in mMCC do not appear durable off treatment, including in patients who achieve a CR, though response to retreatment is promising. Extended duration of treatment needs to be investigated to optimise long-term outcomes.

Keywords: Durability of response; Immune checkpoint inhibitors; Merkel cell carcinoma; Retreatment; Treatment cessation.

MeSH terms

Carcinoma, Merkel Cell* / drug therapy
Carcinoma, Merkel Cell* / pathology
Humans
Immune Checkpoint Inhibitors / adverse effects
Progression-Free Survival
Retrospective Studies
Skin Neoplasms* / drug therapy
Skin Neoplasms* / pathology
Withholding Treatment

Substances

Immune Checkpoint Inhibitors