Y J L Jansen1, E A Rozeman2, R Mason3, S M Goldinger4, M H Geukes Foppen2, L Hoejberg5, H Schmidt6, J V van Thienen2, J B A G Haanen2, L Tiainen7, I M Svane8, S Mäkelä9, T Seremet10, A Arance11, R Dummer12, L Bastholt5, M Nyakas13, O Straume14, A M Menzies15, G V Long15, V Atkinson16, C U Blank2, B Neyns10. 1. Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussel, Belgium. Electronic address: Yanina.Jansen@uzbrussel.be. 2. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Medical Oncology, Princess Alexandra Hospital, Brisbane; Greenslope Oncology, Greenslope Private Hospital, Brisbrane. 4. Melanoma Institute Australia and The University of Syndey, Sydney, Australia; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 5. Department of Oncology, Odense University Hospital, Odense. 6. Department of Oncology, Aarhus Universitet, Aarhus, Denmark. 7. Department of Oncology, Tampere University Hospital, Tampere, Finland. 8. Department of Oncology, Copenhagen University Hospital, Herlev, Denmark. 9. Department of Oncology, University of Helsinki, Helsinki, Finland. 10. Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussel, Belgium. 11. Department of Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain. 12. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 13. Department of Clinical Cancer Research, Oslo University Hospital, Oslo. 14. Department of Oncology, Universitetet Bergen, Bergen, Norway. 15. Melanoma Institute Australia and The University of Syndey, Sydney, Australia; Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney; Department of Medical Oncology, Mater Hospital, Sydney, Australia. 16. Greenslope Oncology, Greenslope Private Hospital, Brisbrane; Department of Medical Oncology, Princess Alexandra Hospital, Brisbane.
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).
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 melanomapatients 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 melanomapatients 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).
Authors: Liudmila V Fedorova; Kirill V Lepik; Natalia B Mikhailova; Elena V Kondakova; Yuri R Zalyalov; Vadim V Baykov; Elena V Babenko; Andrey V Kozlov; Ivan S Moiseev; Boris V Afanasyev Journal: Ann Hematol Date: 2021-02-02 Impact factor: 3.673
Authors: Allison Betof Warner; Jessica S Palmer; Alexander N Shoushtari; Debra A Goldman; Katherine S Panageas; Sara A Hayes; Raazi Bajwa; Parisa Momtaz; Margaret K Callahan; Jedd D Wolchok; Michael A Postow; Paul B Chapman Journal: J Clin Oncol Date: 2020-02-13 Impact factor: 44.544
Authors: Timo E Schank; Andrea Forschner; Michael Max Sachse; Antonia Dimitrakopoulou-Strauss; Christos Sachpekidis; Albrecht Stenzinger; Anna-Lena Volckmar; Alexander Enk; Jessica C Hassel Journal: Cancers (Basel) Date: 2021-05-26 Impact factor: 6.639
Authors: Johannes Kleemann; Manuel Jäger; Eva Valesky; Stefan Kippenberger; Roland Kaufmann; Markus Meissner Journal: Cancer Manag Res Date: 2021-07-15 Impact factor: 3.989