Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma
- 1 July 2019
- journal article
- research article
- Published by Elsevier BV in Annals Of Oncology
- Vol. 30 (7), 1154-1161
- https://doi.org/10.1093/annonc/mdz110
Abstract
Background Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. Patients and Methods This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N=167) or nivolumab (N=18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. Results Median time on treatment was 12months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. Conclusions In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. Clinical trial registration NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3)Keywords
This publication has 18 references indexed in Scilit:
- Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III TrialJournal of Clinical Oncology, 2018
- Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III TrialsJournal of Clinical Oncology, 2017
- Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced MelanomaJournal of Clinical Oncology, 2017
- PD-1 and PD-L1 antibodies in cancer: current status and future directionsCancer Immunology, Immunotherapy, 2017
- Correlation between baseline characteristics and clinical outcome of patients with advanced melanoma treated with pembrolizumab (PEMBRO)Annals of Oncology, 2016
- Combined Nivolumab and Ipilimumab or Monotherapy in Untreated MelanomaThe New England Journal of Medicine, 2015
- Nivolumab in Previously Untreated Melanoma withoutBRAFMutationThe New England Journal of Medicine, 2015
- Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving NivolumabJournal of Clinical Oncology, 2014
- Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer ImmunotherapyClinical Cancer Research, 2011
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010