Nature and management of melanoma recurrences following adjuvant anti-PD-1 (PD1) therapy.

Rachel Woodford Melanoma Institute Australia, Wollstonecraft, Australia info_outline Rachel Woodford, Janet McKeown, Lotte Hoeijmakers, Joanna Mangana, Celeste Lebbe, Farzana Yasmin Zaman, Francisco Aya, John Marsiglio, Rachel S Goodman, Victoria Rayson, Joanna Placzke, Jolien Isabel Kessels, Egle Ramelyte, Waqas Haque, Isabella Wilson, Claudia Trojaniello, Rachel Roberts-Thomson, Caroline Robert, Georgina V. Long, Alexander M. Menzies

Authors Rachel Woodford Melanoma Institute Australia, Wollstonecraft, Australia info_outline Rachel Woodford, Janet McKeown, Lotte Hoeijmakers, Joanna Mangana, Celeste Lebbe, Farzana Yasmin Zaman, Francisco Aya, John Marsiglio, Rachel S Goodman, Victoria Rayson, Joanna Placzke, Jolien Isabel Kessels, Egle Ramelyte, Waqas Haque, Isabella Wilson, Claudia Trojaniello, Rachel Roberts-Thomson, Caroline Robert, Georgina V. Long, Alexander M. Menzies Organizations Melanoma Institute Australia, Wollstonecraft, Australia, Netherlands Cancer Institute (NKI), Amsterdam, Netherlands, Department of Dermatology, University Hospital of Zurich, Zürich, Switzerland, APHP St Louis, Paris, France, Alfred Health, Melbourne, VIC, Australia, Hospital Clínic Barcelona, Barcelona, Spain, Univeristy of Utah, Salt Lake City, UT, Vanderbilt University School of Medicine, Nashville, TN, Peter MacCallum Cancer Centre, Melbourne, Australia, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland, UZ Brussel, Vrije Universiteit Brussel, Brussel, Belgium, Massachusetts General Hospital, Boston, MA, New York University Langone, New York, NY, Crown Princess Mary Cancer Centre Westmead, Westmead, Australia, Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione "G. Pascale", Naples, Italy, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Woodville South, Australia, Gustave Roussy, Villejuif, France, The University of Sydney, Sydney, NSW, Australia, Melanoma Institute Australia, Wollstonecraft, NSW, Australia Abstract Disclosures Research Funding No funding received None. Background: Despite improved outcomes with the use of adjuvant PD1 therapy, approximately 50% of patients (pts) develop recurrent disease by 5 years. Data to define best management of recurrences is lacking, including whether retreatment with PD1 has benefit. Methods: This was a multicentre, international retrospective study of pts with resected stage II-IV melanoma who commenced adjuvant PD1 therapy before January 2022 and then recurred. Demographics, disease characteristics, treatment, toxicity, recurrence patterns, management and outcomes were collected. Results: 711 pts from 17 sites were included. Med age was 60 [range 16-92], 64% (N=451) were male. 641 (91%) pts were stage III (A 7%, B 24%, C 54%, D 3%), 18 (2%) stage II, 51 (7%) stage IV. 80% (N=536) underwent SLNB prior to PD1, of which 44% (N=236) went onto CLND. 635 pts (90%) received PD1, 74 (10%) PD1 + other. Med time to recurrence was 6.2 months (m) (0-68.5); 63% (N=444) recurred ON PD1, while 36% (N=257) recurred OFF. 338 pts (48%) recurred within 6m of starting adjuvant, 166 (23%) between 6-12m, 140 (20%) 12-24m and 59 (8%) after 24m. Initial recurrences were locoregional (LR) alone in 315 (44%), 307 (43%) distant alone, and 78 (11%) both. Patients with LR recurrences alone underwent definitive surgery, or surgery + radiation in 98 (31%) and 42 (13%) respectively. After initial LR management, 164 (52%) had a further local and 129 (41%) distant recurrence. Those with initial distant recurrences were managed with definitive surgery (21, 7%), surgery + radiation (8, 3%) and radiation alone (14, 5%). Further ‘second’ adjuvant therapy was given in 27% (N=86) of LR and 6% (N=25) of distant recurrences. Definitive systemic therapy at first recurrence was given in 77% (N=296) distant and 23% (N=73) LR recurrences (Table). Conclusions: Patients recurring after adjuvant PD1 therapy do so early, and often while on drug. Patients with resected recurrences often receive “second adjuvant” therapy, although whether adjuvant or definitive, outcomes are poor. Novel drug therapies and clinical trials are required for those who recur despite PD1 therapy. Second adjuvant (N=119) RFS2*† DMFS2*† PFS2*† OS* BRAF/MEKi (N=62) 24.9 (7.8-66.0) 16.2 (5.0-42.3) 15.3 (0.5-42.3) 23.4 (1.3-56.8) PD1 (N=42) 11.7 (2.9-58.1) 3.7 (1.3-24.3) 9.0 (1.2-44.0) 19.9 (0.7-76.1) (ON PD1; N=23) 3.2 (0.5-22.8) 18.1 (0.7-76.1) 6.8 (0.7-47.5) 27.0 (0.7-76.1) (OFF PD1; N=19) 17.5 (2.6-52.5) 17.5 (2.6-72.7) 13.3 (2.9-61.2) 16.6 (5.5-72.7) Definitive systemic therapy (N=378) ORR (%) DOR* PFS* OS* PD1 alone (N=46) 24 6.3 (2.7-14.4) 17.4 (2.3-44.3) 15.2 (1.0-69.7) (ON PD1, N=18) 17 11.9 (9.8-14.0) 9.4 (1.4-54.8) 21.3 (3.0-54.8) (OFF PD1, N=28) 32 - 7.9 (2.7-34.0) 11.5 (3.3-51.1) CTLA4 alone (N=19) 11 - 9.8 (4.9-50.5) 12.7 (2.0-35.7) CTLA4 + PD1 (N=157) 34 5.6 (0-21.7) 13.5 (1.9-55.3) 14.4 (1.0-69.7) BRAF/MEKi (N=105) 65 3.4 (0-29.3) 14.8 (0.6-73.5) 15.6 (1.3-67.4) *Med (range), m. †From start of second adjuvant, m.