LBA41 Long-term survival with neoadjuvant therapy in melanoma: Updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)

Long GV, Blank CU, Amaria RN, Hieken TJ, Sandhu SK, Barros MJ, Mitchell TCC, Eroglu Z, Samoylenko IV, Rutkowski P, Johnson D, Pires da Silva I, Perry KA, Tawbi HA, Block MS, Ascierto PA, Burton E, van Akkooi ACJ, Scolyer RA, Menzies AM. Annals of Oncology, 35(Sep 24 2024): S1232, doi:10.1016/j.annonc.2024.08.2282.

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.

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.