Trials find response evaluation of systemic neoadjuvant treatment in patients with stage III melanoma can guide further treatment options.

One advantage of neoadjuvant treatment is that the pathologic response is a fast efficacy readout and surrogate outcome marker for survival that could guide further treatment decisions including the extent of surgery or the necessity of adjuvant systemic treatment. Using survival data from two prospective trials, OpACIN-neo (NCT02977052) and PRADO (NCT02977052), the International Neoadjuvant Melanoma Consortium evaluated the possibility of response-directed treatment personalization. The study, presented by Irene Reijers, PhD-candidate, aimed to answer two questions: do all patients need extensive surgery (ie, total lymph node dissection [TLND]) and do all patients need adjuvant therapy?

In OpACIN-neo, 86 participants were treated with different neoadjuvant regimes followed by TLND and no adjuvant therapy. In PRADO, 99 participants were treated with neoadjuvant therapy (1 mg/kg ipilimumab; 3 mg/kg nivolumab) followed by response evaluation in the index lymph node. The response in this lymph node guided further treatment (ie, TLND, adjuvant treatment).

Of 112 participants with major pathologic response (MPR), 53 underwent a TLND and 59 did not. None of these patients received systemic adjuvant therapy. TLND did not affect survival outcomes: relapse-free survival (RFS) after 3 years was 96% with TLND and 93% without TLND; distant metastases-free survival (DMFS) after 3 years was 98% in both groups.

Of 40 patients with pathologic non-response (pNR), all underwent TLND, 17 received systemic adjuvant therapy, and 23 did not. Adjuvant systemic therapy improved 3-year survival: RFS was 64% versus 35%, and DMFS was 70% versus 52% with or without adjuvant systemic therapy, respectively. The addition of adjuvant radiotherapy to adjuvant systemic therapy in these patients did not improve survival. However, adjuvant radiotherapy improved survival in participants not receiving systemic adjuvant therapy.

Based on these results, Reijers concluded, “In patients with MPR, TLND can probably be omitted without affecting survival outcomes. Whereas patients with MPR do not need adjuvant systemic treatment, patients with pNR benefit from adjuvant systemic treatment. Adjuvant radiotherapy might be beneficial for patients not eligible for adjuvant systemic treatment.”

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