Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma

Y J L Jansen, E A Rozeman, R Mason, S M Goldinger, M H Geukes Foppen, L Hoejbergs, H Schmidt, J V van Thienen, J B A G Haanen, L Tiainen, I Marie Svane, S Mäkelä, T Seremet, A Arance, R Dummer, L Bastholt, M Nyakas, O Straume, A M Menzies, G V LongV Atkinson, C U Blank, B Neyns

161 Citations (Scopus)

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 12 months (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 18 months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (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 >6 months, 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).

Original languageEnglish
Article numbermdz110
JournalAnnals of Oncology
Volume30
Issue number7
Pages (from-to)1154-1161
Number of pages8
ISSN0923-7534
DOIs
Publication statusPublished - Jul 2019

Keywords

  • anti-PD-1 therapy
  • duration of treatment
  • immunotherapy
  • melanoma

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