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

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  • 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 Long
  • V Atkinson
  • C U Blank
  • B Neyns
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BACKGROUND: 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 to 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 anti-tumour 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 to clinical trials. In patients obtaining a CR, and being treated for more than 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 anti-tumour activity in some patients.Clinical trial registration: NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3).

OriginalsprogEngelsk
TidsskriftAnnals of Oncology
ISSN0923-7534
DOI
StatusUdgivet - jul. 2019

Bibliografisk note

© The Author 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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