Some patients with stage III melanoma can avoid surgery after neoadjuvant immunotherapy
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CHICAGO — Tumor lymph node dissection likely can be omitted for patients with melanoma who achieve major pathologic response after neoadjuvant immune checkpoint blockade, according to study results presented at ASCO Annual Meeting.
Patients who achieve major pathologic response do not need adjuvant systemic therapy; however, adjuvant systemic therapy appears to extend survival for patients who do not achieve pathologic response, researchers concluded.
Prior studies showed neoadjuvant immune checkpoint blockade with ipilimumab (Yervoy, Bristol Myers Squibb), an anti-CTLA-4 antibody, and nivolumab (Opdivo, Bristol Myers Squibb), an anti-PD-1 antibody, induced high rates of pathologic response among patients with high-risk stage III melanoma. Pathologic response is associated with favorable RFS rates in this population.
The next steps toward personalization of therapy in stage III melanoma require answering three questions, according to Irene Reijers, a PhD student at Netherlands Cancer Institute. They are: Do all patients need extensive surgery? Do all patients require adjuvant therapy? If so, which regimen is best?
Reijers and colleagues compared data from two trials to determine whether omitting tumor lymph node dissection for patients with major pathologic response negative affected long-term survival. They also examined whether the addition of adjuvant systemic therapy for patients who did not achieve pathologic response improved survival.
The OpACIN-neo trial assessed three ipilimumab-nivolumab combinations followed by therapeutic lymph node dissection with no adjuvant systemic therapy.
The PRADO trial evaluated a personalized approach in which patients who achieved major pathologic response did not receive tumor lymph node dissection or adjuvant systemic therapy. Patients who did not achieve pathologic response underwent tumor lymph node dissection followed by adjuvant systemic therapy with or without radiotherapy.
Researchers analyzed 3-year RFS and distant-metastasis-free survival among participants in both trials, comparing outcomes among patients who achieved major pathologic response with vs. without tumor lymph node dissection, and among patients without pathologic response based on whether they received adjuvant systemic therapy.
Median follow-up was 37.9 months in the PRADO trial and 46.8 months in the OpACIN-neo trial.
Among patients who achieved major pathologic response, a personalized strategy that omitted tumor lymph node dissection did not adversely affect 3-year RFS (96% with dissection vs. 93% without) or 3-year distant-metastasis-free survival (98% in both groups).
Among patients who had not achieved pathologic response, researchers reported numerical differences in 3-year RFS (64% vs. 35%) and 3-year distant-metastasis-free survival (70% vs. 52%) among those who received adjuvant systemic therapy in the form of ongoing anti-PD-1 therapy or a switch to BRAF/MEK inhibitor therapy; however, the differences did not reach statistical significance.
Perspective
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Philip Friedlander, MD
Over the past several years, the FDA has approved the use of anti-PD-1 immunotherapy and BRAF inhibitor/MEK inhibitor targeted therapy for a year with survival benefits. Data presented in the PRADO and OACIN-neo studies support benefit from use of immunotherapy in the neoadjuvant setting. Importantly, the data suggest the degree of response could affect subsequent management — specifically the need for completion lymph node dissection. Removing the need for completion nodal dissection for certain patients is important, as it removes surgical risks and risks for lymphedema. Further investigation of these approaches is needed, ideally in prospective randomized trials.
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Reijers ILM, et al. Abstract 101. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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