Long-term survival with neoadjuvant therapy in melanoma: Updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)

Abstract

BACKGROUND: Neoadjuvant therapy is the standard of care for resectable stage >=IIIB melanoma. In 2021, the International Neoadjuvant Melanoma Consortium published a pooled analysis of 196 melanoma pts treated with neoadjuvant immunotherapy (ICI) or BRAF/MEK targeted therapy. Here, we provide a survival update of an expanded cohort. METHODS: Clinical, radiographic, histopathological, and survival data were collated for pts with resectable stage >=IIIB melanoma who received neoadjuvant therapy in a clinical trial or routine care. Outcomes included major pathological response (MPR) rate, event-free survival (EFS; progression prior to surgery, recurrence post-surgery or death), and recurrence-free survival (RFS). RESULTS: Data was retrieved from 818 pts with stage >=IIIB melanoma; 633 (77%) trial pts and 185 (23%) real-world pts. Median age 59 yrs (range, 18-92), 38% females, 45% IIIB, 38% IIIC, 2% IIID, 11% IIIB-D undefined, and 2% IV. Median follow-up was 3.0 yrs (range, 0.05-11). Pts received neoadjuvant ICI (N=610; 169 PD1 alone, 351 PD1+CTLA4, 59 PD1+LAG3, 27 PD1+other IO, 4 CTLA4 alone), BRAF/MEK (N=88), or ICI + Target Therapy (TT) (N=120). The MPR and RFS rates (for pts who underwent TLND or index node resection), and EFS rates (for total population) differed by treatment regimen (Table); OS data is still maturing. Within the ICI cohort, 3-yr EFS was 64% (95% CI 55-7367) with PD1 alone, 76% (95% CI 72-81) with PD1+CTLA4, and 82% (95% CI 70-95) with PD1+LAG3. For pts with PD1+other IO (median follow-up, 1.7 yrs [range, 0.7-3.2]), 1.5-yr EFS was 95% (95% CI 86-100). Additional correlations will be presented. [Formula presented] CONCLUSIONS: Neoadjuvant combination ICI provides an unprecedented and lasting survival benefit to pts with resectable stage >=IIIB melanoma, particularly those who achieve MPR. Those with pNR, and likely pPR, will need alternative approaches.