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Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).

Researchers

Georgina V Long, Inês Pires da Silva, Kristen A Perry, Jurriaan Romano, Serigne N Lo, Piyush Grover, Paolo A Ascierto, Rodabe N Amaria, Tina J Hieken, Caroline Robert, Lucie Heinzerling, Shahneen Sandhu, Milton Barros, Tara C Mitchell, Zeynep Eroglu, Igor V Samoylenko, Lukas Flatz, Céleste Lebbé, Douglas B Johnson, Piotr Rutkowski, Eva Muñoz-Couselo, Omid Hamid, Claudia Trojaniello, Domenico Mallardo, Matthew S Block, Naima Hammoudi, Naima Benannoune, Dirk Tomsitz, Yang Wang, Cigdem Dinckal, Angelina Kuzmenko, Andrea Forschner, Matteo S Carlino, Mathilde Jalving, Michael A Postow, P Francesco Ferrucci, Ellen Kapiteijn, Astrid A M van der Veldt, Karijn P M Suijkerbuijk, Laetitia da Meda, Hannah Burnette, Anna Czarnekca, Inderjit Mehmi, Geke Hospers, Sarah Lochrin, Alexander C J van Akkooi, Hussein A Tawbi, Elizabeth M Burton, Michael T Tetzlaff, Bart A van de Wiel, Robert V Rawson, Christian U Blank, Alexander M Menzies

Abstract

Neoadjuvant immune checkpoint inhibitors (ICIs) are standard of care for resectable stage IIIB-D melanoma, but knowledge gaps remain regarding optimal treatment type, long-term survival, postsurgical management and clinical, histopathological or molecular subgroups. We analyzed 1,038 patients treated with neoadjuvant ICIs (n = 735), BRAF and MEK inhibitors (BRAF/MEKis; n = 119) or ICI plus any targeted therapy (ICI + TT; n = 184) from 26 international sites in both trial (755, 72.7%) and nontrial (283, 27.3%) settings. ICI regimens included anti-programmed cell death protein 1 (PD-1) alone (PD-1 alone; n = 242) and anti-PD-1 plus other immuno-oncology agent(s) (PD-1 + IO; n = 489). Outcomes included major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). An MPR was achieved in 57.8% of patients with ICIs, 51.4% with BRAF/MEKis and 44.6% with ICI + TT. PD-1 + IO elicited higher MPR rates than PD-1 alone (61.4% versus 49.5%). The 5-year RFS rate was 61.0% with PD-1 alone, 73.9% with PD-1 + IO, 37.4% with BRAF/MEKis and 76.4% with ICI + TT; the 5-year OS rates were 83.3%, 87.5%, 69.8% and 83.9%, respectively. ICI-treated patients with MPR had 5-year OS rates of 98.8% with PD-1 alone and 97.9% with PD-1 + IO and gained no benefit from continuing ICIs into the adjuvant setting. Neoadjuvant ICIs were active in BRAF-mutant melanoma (MPR, 46.3%), acral melanoma (38.1%), in-transit metastases (66.7%) and oligometastases (41.2%), although subgroup sizes and relative effectiveness varied. Survival outcomes were excellent with neoadjuvant ICIs, particularly in patients achieving MPR, but poor with BRAF/MEKis and mixed with ICI + TT. Predictive biomarker-driven trials, effective adjuvant strategies and subgroup-specific research are needed for nonresponders.
Source: PubMed (PMID: 42823486)View Original on PubMed