Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy☆

C N Owen; A N Shoushtari; D Chauhan; D J Palmieri; B Lee; M W Rohaan; J Mangana; V Atkinson; F Zaman; A Young; C Hoeller; P Hersey; R Dummer; M A Khattak; M Millward; S P Patel; A Haydon; D B Johnson; S Lo; C U Blank; S Sandhu; M S Carlino; J M G Larkin; A M Menzies; G V Long

doi:10.1016/j.annonc.2020.04.471

Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy^☆

Ann Oncol. 2020 Aug;31(8):1075-1082. doi: 10.1016/j.annonc.2020.04.471. Epub 2020 May 6.

Authors

C N Owen¹, A N Shoushtari², D Chauhan³, D J Palmieri⁴, B Lee⁵, M W Rohaan⁶, J Mangana⁷, V Atkinson⁸, F Zaman⁹, A Young¹⁰, C Hoeller¹¹, P Hersey¹, R Dummer⁷, M A Khattak¹², M Millward¹³, S P Patel¹⁴, A Haydon⁹, D B Johnson¹⁰, S Lo¹, C U Blank⁶, S Sandhu⁵, M S Carlino¹⁵, J M G Larkin³, A M Menzies¹⁶, G V Long¹⁷

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
² Memorial Sloan Kettering Cancer Center, New York, USA.
³ The Royal Marsden NHS Foundation Trust, London, UK.
⁴ Westmead Hospital and Blacktown Hospitals, Sydney, Australia.
⁵ Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia.
⁶ Netherlands Cancer Institute, Amsterdam, Netherlands.
⁷ University Hospital Zurich, Zürich, Switzerland.
⁸ Greenslopes Private Hospital, Princess Alexandra Hospital and The University of Queensland, Brisbane, Australia.
⁹ The Alfred Hospital, Melbourne, Australia.
¹⁰ Vanderbilt University Medical Center, Nashville, USA.
¹¹ Medical University of Vienna, Vienna, Austria.
¹² Fiona Stanley Hospital, The University of Western Australia, Perth, Australia.
¹³ School of Medicine and Pharmacology, Nedlands, Australia.
¹⁴ The University of Texas MD Anderson Cancer Center, Houston, USA.
¹⁵ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Westmead Hospital and Blacktown Hospitals, Sydney, Australia.
¹⁶ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia.
¹⁷ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia. Electronic address: [email protected].

Abstract

Background: Anti-programmed cell death protein 1 (PD-1) antibodies (PD1) prolong recurrence-free survival in high-risk resected melanoma; however, approximately 25%-30% of patients recur within 1 year. This study describes the pattern of recurrence, management and outcomes of patients who recur with adjuvant PD1 therapy.

Patients and methods: Consecutive patients from 16 centres who recurred having received adjuvant PD1 therapy for resected stage III/IV melanoma were studied. Recurrence characteristics, management and outcomes were examined; patients with mucosal melanoma were analysed separately.

Results: Melanoma recurrence occurred in 147 (17%) of ∼850 patients treated with adjuvant PD1. In those with cutaneous melanoma (n = 136), median time to recurrence was 4.6 months (range 0.3-35.7); 104 (76%) recurred during (ON) adjuvant PD1 after a median 3.2 months and 32 (24%) following (OFF) treatment cessation after a median 12.5 months, including in 21 (15%) who ceased early for toxicity. Fifty-nine (43%) recurred with locoregional disease only and 77 (57%) with distant disease. Of those who recurred locally, 22/59 (37%) subsequently recurred distantly. Eighty-nine (65%) patients received systemic therapy after recurrence. Of those who recurred ON adjuvant PD1, none (0/6) responded to PD1 alone; 8/33 assessable patients (24%) responded to ipilimumab (alone or in combination with PD1) and 18/23 (78%) responded to BRAF/MEK inhibitors. Of those who recurred OFF adjuvant PD1, two out of five (40%) responded to PD1 monotherapy, two out of five (40%) responded to ipilimumab-based therapy and 9/10 (90%) responded to BRAF/MEK inhibitors.

Conclusions: Most patients who recur early despite adjuvant PD1 develop distant metastases. In those who recur ON adjuvant PD1, there is minimal activity of further PD1 monotherapy, but ipilimumab (alone or in combination with PD1) and BRAF/MEK inhibitors have clinical utility. Retreatment with PD1 may have activity in select patients who recur OFF PD1.

Keywords: adjuvant therapy; immunotherapy; melanoma.

MeSH terms

Combined Modality Therapy
Humans
Immunotherapy
Ipilimumab / therapeutic use
Melanoma* / drug therapy
Skin Neoplasms* / drug therapy

Substances

Ipilimumab

Abstract

MeSH terms

Substances

Grants and funding