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Early Melanoma Recurrence to Adjuvant Anti-PD-1 Therapy

Findings from 16 centres worldwide
07 May 2020
Cancer Immunology and Immunotherapy;  Melanoma and other skin tumours

Patterns of recurrence, management and outcomes of melanoma patients with recurrence to adjuvant anti-PD1 therapy was described by Prof. Georgina Long of the Melanoma Institute Australia, University of Sydney, Sydney, Australia and colleagues in an international study published online on 6 May 2020 in the Annals of Oncology. Recurrence occurred in 17% of melanoma patients after a median 4.6 months after starting adjuvant PD1 therapy. At initial recurrence, the study team found that 57% of patients had distant metastases and 38% of patients with initially local recurrence further recurred distantly within a short follow-up period.

The authors described in the study background that treatment with anti-PD1 therapy prolongs recurrence-free survival in patients with resected high-risk melanoma. Within one year the recurrence rate is around 25-30%. They studied the characteristics of patients with recurrence recorded after adjuvant anti-PD1 therapy for resected stage III/IV melanoma in 16 centres across the world. Patients with mucosal melanoma were analyzed separately.

The study data were previously reported at ASCO 2019 Annual Meeting. In the article published now in the Annals of Oncology, the study team reported that melanoma recurrence occurred in 147 of 850 patients (17%) treated with adjuvant anti-PD1 therapy. In 136 patients with cutaneous melanoma, median time to recurrence was 4.6 months (range 0.3-35.7).

In total 104 patients (76%) recurred during adjuvant anti-PD1 therapy after a median 3.2 months. Furthermore, 32 patients (24%) recurred following treatment cessation after a median 12.5 months, including 21 patients (15%) who ceased early treatment due to toxicity.

In total, 59 patients (43%) recurred with locoregional disease only and 77 patients (57%) with distant disease. Of those who recurred locally, 22 patients (37%) subsequently recurred distantly.

Systemic therapy after recurrence was offered to 89 patients (65%). Of those who recurred during adjuvant anti-PD1 therapy, none (0 of 6 patients) responded to anti-PD1 therapy alone, 8 of 33 evaluable patients (24%) responded to ipilimumab alone or in combination with anti-PD1 therapy and 18 of 23 patients (78%) responded to BRAF/MEK inhibitors. Of those patients who recurred after adjuvant anti-PD1 therapy, 2 of 5 patients (40%) responded to anti-PD1 monotherapy, 2 of 5 patients (40%) responded to ipilimumab-based therapy and 9 of 10 patients (90%) responded to BRAF/MEK inhibitors.

The authors concluded that in patients with melanoma recurrence recorded during adjuvant anti-PD1 therapy, there is a minimal activity of further PD1 monotherapy. However, ipilimumab alone or in combination with PD1 antibody and BRAF/MEK inhibitors have clinical utility in this setting. Retreatment with anti-PD1 therapy may have activity in selected patients with recurrence happening following anti-PD1 therapy.

No funding for this study was declared.

Reference

Owen CN, Shoushtari AN, Chauhan D, et al. Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy. Annals of Oncology; Published online 6 May 2020.  DOI: https://doi.org/10.1016/j.annonc.2020.04.471.

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