Journal Article

PET/CT scan and biopsy-driven approach for safe anti-PD-1 therapy discontinuation in patients with advanced melanoma

Shand, Shelly, Rapisuwon, Suthee, Atkins, Michael B., Radfar, Arash, Gardner, Kellie, Swoboda, David, Reilly, Michael J., Zaemes, Jacob, Petronic-Rosic, Vesna, Al-Refaie, Waddah B., Gibney, Geoffrey T., Shah, Neil J.

2021

Overview

BackgroundLimited data exist on safe discontinuation of antiprogrammed cell death protein 1 (PD-1) therapy in responding patients with advanced melanoma. The use of 18fluorodeoxyglucose (18FDG)-PET/CT scan and tumor biopsy for assessment of active disease may be an effective predictive biomarker to guide such treatment decisions.MethodsA retrospective study of 122 patients with advanced melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anticytotoxic T-lymphocyte-associated protein 4 combination therapy at Georgetown Lombardi Comprehensive Cancer Center was conducted. Uveal melanoma patients and those receiving concurrent experimental therapy were excluded. Baseline characteristics, treatment outcomes, and survival were analyzed. Patients who decided to come off treatment typically after 12 months using CT scan radiographic complete response (CR), 18FDG-PET/CT scan complete metabolic response (CMR) or tumor biopsy of a non-CR/CMR tumor site negative for active disease (possible pathological CR) were identified and compared with patients who discontinued treatment due to toxicity while their disease was in control. Event-free survival (EFS) was assessed from the last dose of anti-PD-1 therapy to progression requiring subsequent treatment (surgery, radiation, and/or systemic therapy) or referral to hospice/death due to melanoma.Results24 (20%) patients discontinued treatment by choice with no active disease and 28 (23%) patients discontinued treatment due to toxicity with disease control after 12-month and 4-month median treatment durations, respectively. Similar baseline characteristics were observed between cohorts except higher prior receipt of ipilimumab (29% vs 7%; p=0.036) and fewer BRAF mutant positive disease (17% vs 41%; p=0.064) in patients off treatment by choice. Three-year EFS rates were 95% and 71%, respectively. No significant associations between EFS and sex, disease stage, lactate dehydrogenase elevation, BRAF status, prior systemic therapy, ECOG performance status, presence of brain metastases, or combination versus monotherapy were observed. Tumor biopsies led to alternative management in 3/10 patients due to active metastatic melanoma or second malignancy.ConclusionsAnti-PD-1 therapy discontinuation after 12 months when no active disease is observed on CT scan, PET/CT scan or tumor biopsy may have low rates of disease relapse in patients with advanced melanoma. Biopsy of residual disease may frequently lead to a change in management. These findings are undergoing validation in the EA6192 trial.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Aged / Apoptosis / Biopsy / Biopsy - methods / Brain cancer / Cancer / Cancer therapies / Cell death / Disease control / Female / Humans / Immunotherapy / Immunotherapy - methods / Immunotherapy Biomarkers / Male / Medical imaging / Melanoma / Melanoma - diagnostic imaging / Melanoma - drug therapy / Metabolism / Middle Aged / Monoclonal antibodies / Positron Emission Tomography Computed Tomography - methods / programmed cell death 1 receptor / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Retrospective Studies / Tomography / Treatment Outcome / tumor biomarkers