In patients with melanoma who are undergoing neoadjuvant therapy with immune checkpoint blockade, response to treatment may guide the intensity of additional treatment, according to a retrospective analysis of two major trials presented by Irene L.M. Reijers, an MD/PhD candidate in the Christian Blank Group at the Netherlands Cancer Institute, Amsterdam.1 These findings were presented at the 2023 ASCO Annual Meeting.
After receiving ipilimumab plus nivolumab, patients who achieved a major pathologic response derived no additional benefit from therapeutic lymph node dissection in terms of recurrence-free survival or distant metastasis–free survival. Furthermore, adjuvant systemic therapy also proved to be of little benefit in this group, given their high survival rates. On the other hand, patients who did not respond well to neoadjuvant immune checkpoint blockade had better survival outcomes with adjuvant systemic therapy, which involved ongoing anti–PD-1 therapy or a switch to BRAF/MEK inhibition, she reported.
As Ms. Reijers explained, in high-risk stage III melanoma, neoadjuvant ipilimumab plus nivolumab induces high pathologic response rates, which portend an excellent relapse-free survival. The OpACIN-neo trial tested different neoadjuvant ipilimumab/nivolumab regimens followed by therapeutic lymph node dissection without adjuvant systemic therapy.2 The PRADO trial tested a personalized approach in which patients achieving a major pathologic response (≤ 10% viable tumor) did not undergo therapeutic lymph node dissection or adjuvant systemic therapy, whereas those without a pathologic response (> 50% viable tumor) were treated with therapeutic lymph node dissection followed by adjuvant systemic therapy (BRAF/MEK inhibitors or anti–PD-1), with or without radiotherapy.3
Adjuvant anti–PD-1 therapy might be preferable for long-term outcomes in stage III melanoma.— Irene L.M. Reijers
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The study conducted by Ms. Reijers compared the nonpersonalized approach of OpACIN-neo (n = 86) and the response-directed approach of PRADO (n = 99) to address the following questions: Does omission of therapeutic lymph node dissection after a major pathologic response have an adverse effect on long-term survival? Does the addition of adjuvant systemic therapy in patients without pathologic responses have a favorable effect on survival? And what is the best adjuvant treatment regimen: anti–PD-1, BRAF/MEK inhibition, or radiotherapy? Patients with BRAF mutations received dabrafenib plus trametinib, whereas those without such mutations received nivolumab; a small number of patients received radiation therapy.
Investigators analyzed the 3-year recurrence-free survival and distant metastasis–free survival according to response and treatment—ie, with and without therapeutic lymph node dissection and with and without adjuvant systemic therapy. At a median follow-up of 47 months in OpACIN-neo and 38 months in PRADO, the analysis showed the following results:
In patients with a major pathologic response, omission of therapeutic lymph node dissection did not affect survival. For patients without therapeutic lymph node dissection vs with therapeutic lymph node dissection, the 3-year recurrence-free survival was 93% vs 96% (P = .47), and the 3-year distant metastasis–free survival was 98% vs 98% (P = .92), respectively.
In patients without a pathologic response, systemic therapy provided a nonsignificant numerical benefit. For patients receiving adjuvant systemic therapy vs those without such therapy, the 3-year recurrence-free survival was 64% vs 35% (P = .10), and the distant metastasis–free survival was 70% vs 52% (P = .24), respectively.
In the small subset (n = 17) of patients receiving adjuvant systemic therapy, the 3-year recurrence-free survival was 71% with targeted therapy and 58% with nivolumab alone (P = .78), and the distant metastasis–free survival was 86% and 56% (P = .13), respectively.
In the small subset (n = 11) who received adjuvant radiotherapy, outcomes were improved compared with patients who received no other adjuvant treatment (ie, no systemic therapy at all), with a 3-year recurrence-free survival rate of 75% vs 26% and a distant metastasis–free survival rate of 75% vs 47%, respectively. “Adjuvant radiotherapy might be beneficial for patients who are not eligible for systemic therapy,” she said.
DISCLOSURE: Ms. Reijers reported a financial interest in Signature Oncology.
REFERENCES
1. Reijers ILM, Menzies AM, Versluis JM, et al: The impact of response-directed surgery and adjuvant therapy on long-term survival after neoadjuvant ipilimumab plus nivolumab in stage III melanoma: Three-year data of PRADO and OpACIN-neo. 2023 ASCO Annual Meeting. Abstract 101. Presented June 3, 2023.
2. Versluis JM, Menzies AM, Sikorska K, et al: Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials. Ann Oncol 34:420-430, 2023.
3. Reijers ILM, Menzies AM, van Akkooi ACJ, et al: Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: The PRADO trial. Nat Med 28:1178-1188, 2022.
