Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown.
Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included. Disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcomes were examined.
Eighty-five patients developed recurrent melanoma; nineteen (22%) during adjuvant TT. Median time to first recurrence was 18 months and median follow up from first recurrence was 31 months. Twenty-nine (34%) patients recurred locoregionally, fifty (59%) patients had distant recurrence and six (7%) patients recurred in both sites concurrently. Of those who recurred locoregionally, twenty-three (23/29, 79%) patients underwent surgery to no evidence of disease and fourteen (14/29, 48%) patients later developed distant disease. Twenty-eight (33%) patients had died at census, all due to melanoma. Fifty-eight (68%) patients received immunotherapy (IT) or TT as 1st line systemic therapy at either first or subsequent recurrence and had disease that was assessable for response. Response to anti-PD-1 therapy (+/- trial agent), combination ipilimumab and nivolumab, TT rechallenge and ipilimumab monotherapy was 63%, 62% 25% and 10% respectively. Twenty-eight (33%) patients had died at census, all from melanoma. Median overall survival (OS) from date of first recurrence for all patients was not reached. OS varied by drug class received as 1st line systemic therapy after relapse. Two-year OS was 84% for anti-PD-1 therapy (+/- trial agent), 92% for combination ipilimumab and nivolumab, 49% for TT and 45% for ipilimumab monotherapy (p=0.028).
This study demonstrates that patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 therapy and have outcomes similar to those seen when first line anti-PD-1 therapy is used in stage IV melanoma.