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Giving just two cycles of combination immunotherapy before removing melanoma lymph nodes cut relapses by more than two-thirds compared with a year of standard immunotherapy after surgery, and most patients needed no further treatment.
Open-label phase 3 trial of 423 patients with resectable, macroscopic stage III melanoma randomised to two cycles of neoadjuvant ipilimumab (80 mg) plus nivolumab (240 mg) followed by lymph node dissection, with adjuvant therapy only for those without a major pathological response, or to upfront surgery followed by 12 cycles of adjuvant nivolumab. Primary endpoint was event-free survival.
12-month EFS was 83.7% vs 57.2% (HR 0.32). A major pathological response occurred in 59% of neoadjuvant patients, and 95% of those were event-free at 12 months without any adjuvant therapy. It established neoadjuvant immunotherapy as the standard for macroscopic stage III melanoma and showed that the pathological response can be used to stop treatment early in most patients.
Patients with melanoma that has spread to palpable lymph nodes should now be offered immunotherapy before rather than only after surgery: two cycles of low-dose ipilimumab with nivolumab, then surgery, with the pathology result deciding whether any more treatment is needed. Most patients respond well and are spared a year of adjuvant therapy. Serious side effects are more common than with nivolumab alone, mostly endocrine, and the approach requires close coordination between oncologists, surgeons and pathologists.
Shares John Haanen, Netherlands Cancer Institute (NKI-AvL), Immune-related adverse events (irAEs), CTLA-4.
Shares Stage III melanoma (after surgery), Event-free / disease-free survival (EFS, DFS, iDFS, RFS), CTLA-4, Neoadjuvant / adjuvant / perioperative.
Shares Christian Blank, John Haanen, NADINA, Immune-related adverse events (irAEs).
Shares John Haanen, Immune-related adverse events (irAEs), CTLA-4, Ipilimumab.
Shares Netherlands Cancer Institute (NKI-AvL), CTLA-4, Ipilimumab, Nivolumab.
Shares CTLA-4, Ipilimumab, Bristol Myers Squibb, Nivolumab.
Shares Christian Blank, NADINA, Pathologic complete response (pCR), Neoadjuvant / adjuvant / perioperative.
Shares Surgery and radiotherapy cure most, get least, Neoadjuvant / adjuvant / perioperative, Bristol Myers Squibb, Trial design, endpoints and cost.