Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Efficacy of checkpoint inhibitors (CPIs) in acral melanoma (AM) (#17)

Prachi Bhave 1 2 , Tasnia Ahmed 2 , Alexander Shoushtari 3 , Anne Zaremba 4 , Judith Versluis 5 , Joanna Mangana 6 , Michael Weichenthal 7 , Lu Si 8 , Thierry Lesimple 9 , Caroline Robert 10 , Claudia Trojaniello 11 , Alexandre Wicky 12 , Richard Heywood 13 , Lena Tran 14 , Kathleen Batty 2 , Anna Stansfeld 15 , Celeste Lebbe 16 , Julia K Schwarze 17 , Meghan Mooradian 18 , Matteo S Carlino 1 2
  1. Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia
  2. Melanoma Institute Australia, Sydney, NSW, Australia
  3. Memorial Sloan Kettering Cancer Centre, New York, USA
  4. University Hospital Essen, Essen, Germany
  5. Netherlands Cancer Institute, Netherlands
  6. University Hospital Zürich, Zurich, Switzerland
  7. University of Kiel, Kiel, Germany
  8. Peking University Cancer Hospital & Institute, Beijing, China
  9. Centre Eugène Marqui, Rennes, France
  10. Gustave Roussy and Paris-Saclay Institute, Villejuif, France
  11. Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy
  12. University of Lausanne, Lousanne, Switzerland
  13. University of Manchester, Manchester, UK
  14. Vanderbilt University Medical Center, Tennessee, USA
  15. Freeman Hospital, Newcastle upon Tyne, United Kingdom
  16. Saint-Louis Hospital, Paris, France
  17. Universitair Ziekenhuis Brussel, Brussels, Belgium
  18. Massachusetts General Hospital, Massachusetts, USA

Background:

AM is a rare melanoma subtype with poor prognosis. While retrospective data suggests low activity of PD1 alone, no data is available on the efficacy of combination PD1/CTLA4 in AM. AM primary site is associated with differences in tumour mutation burden, which may impact CPI activity. We examined the efficacy of CPIs in AM, and in primary site subgroups.

Methods:

Patients with unresectable stage III/IV AM treated with ≥1 line of CPI (PD1 and/or ipilimumab (Ipi)) were studied. Disease/patient characteristics and therapy were examined. Multivariable logistic and Cox regression analysis were conducted. Primary outcomes were objective response rate (ORR), progression free survival (PFS) and overall survival (OS).

Results:

369 patients were included; median age at first diagnosis was 63y, 80% Caucasian, 53% male, 12% BRAFm. Median time from primary diagnosis to advanced disease was 19.6 months. Primary site was 260 (70%) plantar, 25 (7%) palmar, 84 (23%) subungual. Excluding 41 patients who received adjuvant CPI, 1st line systemic therapy included 151 (46%) PD1, 51 (15%) Ipi, 54 (16%) combination CPI and 72 (22%) other therapies. At 1st line therapy commencement, 30% were stage M1c, 53% ECOG 0 and 19% elevated LDH. Median follow-up was 8.1y.

ORR was 44%, 26% and 12% for combination CPI, PD1 and CTLA4, respectively (p=0.0015, multivariate analysis). PFS was significantly associated with 1st line therapy, however PFS was not significantly different between PD1 and combination CPI (p=0.42). Median OS was 2.3y (95% CI 1.9-2.6) and did not vary by 1st line therapy (p=0.57). No outcome differences were found between primary site.

Conclusions:

To our knowledge, this is the largest study on CPIs in AM. CPIs are active in advanced AM, with combination CPIs superior to PD1 alone in terms of ORR but not PFS or OS. Primary AM site did not impact CPI efficacy.