Headline: Immunotherapy is moving to the frontlines of localized melanoma treatment paradigms.
The Study: Results of the phase 3 NADINA trial are being shared at ASCO this week where 423 patients undergoing resection for clinically stage III melanoma were randomized to +/- neoadjuvant ipi+nivo. All patients had biopsy-proven nodal disease with no evidence of distant disease on PET Interestingly, all patients in the surgery first group received 12 cycles of adjuvant ipi+nivo, while post-op therapy was “response driven” in the neoadjuvant group where those with a major pathologic response (i.e. <10% viable tumor cells remaining) received no adjuvant therapy and those with a less robust response received 12 cycles of adjuvant ipi+nivo if BRAF-wild type or 46 weeks of daily dabrafenib+trametinib if BRAF-mutated. Remarkably, at a median follow-up just shy of 10 months, there was already a clearly superior event-free survival rate at one year among those in the neoadjuvant arm (84%) versus adjuvant-only arm (57%). Of note, 3 in 5 achieved a major pathologic response after neoadjuvant immunotherapy, among whom the event-free survival at one year surpassed 95% without any adjuvant therapy whatsoever. This is quite a remarkable improvement by simply shifting immune checkpoint inhibition prior to surgery, and the authors note the prevailing hypothesis that: “Stronger and more diverse T-cell responses are induced by … the presence of the entire tumor, and therefore the complete neoantigen repertoire, at the time the immunotherapy is initiated.”
TBL: Patients with clinically node-positive melanoma should be considered for neoadjuvant dual immune checkpoint inhibition. | Blank, N Engl J Med 2024
The Study: Results of the phase 3 NADINA trial are being shared at ASCO this week where 423 patients undergoing resection for clinically stage III melanoma were randomized to +/- neoadjuvant ipi+nivo. All patients had biopsy-proven nodal disease with no evidence of distant disease on PET Interestingly, all patients in the surgery first group received 12 cycles of adjuvant ipi+nivo, while post-op therapy was “response driven” in the neoadjuvant group where those with a major pathologic response (i.e. <10% viable tumor cells remaining) received no adjuvant therapy and those with a less robust response received 12 cycles of adjuvant ipi+nivo if BRAF-wild type or 46 weeks of daily dabrafenib+trametinib if BRAF-mutated. Remarkably, at a median follow-up just shy of 10 months, there was already a clearly superior event-free survival rate at one year among those in the neoadjuvant arm (84%) versus adjuvant-only arm (57%). Of note, 3 in 5 achieved a major pathologic response after neoadjuvant immunotherapy, among whom the event-free survival at one year surpassed 95% without any adjuvant therapy whatsoever. This is quite a remarkable improvement by simply shifting immune checkpoint inhibition prior to surgery, and the authors note the prevailing hypothesis that: “Stronger and more diverse T-cell responses are induced by … the presence of the entire tumor, and therefore the complete neoantigen repertoire, at the time the immunotherapy is initiated.”
TBL: Patients with clinically node-positive melanoma should be considered for neoadjuvant dual immune checkpoint inhibition. | Blank, N Engl J Med 2024