1116P - Long term outcome of complete responders to immune checkpoint inhibitors (ICI) or target therapy (TT) in advanced melanoma

Background

Achieving a CR with ICI or with TT is associated with long-term survival in advanced melanoma pts. This is a retrospective study of the characteristics and long-term outcome of complete responders to ICI or TT.

Methods

Clinical data were collected between October 2010 and July 2022. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox multivariate proportional hazard regression model was applied to analyze association between clinical characteristics and PFS.

Results

A CR was achieved by 197 pts after ICI (anti-PD-1+/-anti-CTLA-4) for 168 (85.3%) and TT (anti-BRAF+/-anti-MEK) for 26 (13.2%) pts respectively. Median follow-up (FU) was 72 months (mos) [range=8;132]. Median duration of treatment (tx) was 11.1 mos [IQR=5.9;19.3] with ICI and 19.4 mos [IQR=8.5;30.4] with TT. Median duration to achieve the 1st CR was 9 mos with ICI and 13.9 mos with TT. Median duration of response was not reached (NR) with ICI and 2.28 mos [95%CI=1.15;NA] with TT. Relapses occurred in 38 (22.6%) and 16 (61.5%) of pts respectively, meaning a significantly higher relapse risk with TT than with ICI (HR=2.58 [95%CI=1.23 ;5.43], p=0.012). Median PFS was NR with ICI and 2.97 mos [95%CI=2.65;NA] with TT. PFS rate at 72 mos was 73.3% with ICI [95%CI=65.84;81.67] and 33.9% with TT [95%CI=18.27;63.21]. Number of lines, LDH, BRAF/NRAS mutation status were not statistically associated with relapse. Relapse occurred during tx in 6 (16.2%) and 8 (53.3%) pts and after tx discontinuation in 31 (83.8%) and 7 (46.4%) pts with ICI and TT respectively. The brain was a site of relapse in 2.9 % and 19.2% of responders to ICI and TT respectively (p: 0.0046, Fisher exact test). Among relapsing pts, 23 pts were rechallenged with ICI and 5 with TT, a new CR occurring in 3 and 2 pts respectively. Median OS was NR in both groups. After a median FU of 72 mos, 87.1% [95%CI=81.38;93.40] pts and 64.6% [95%CI=45.23;92.31] were alive respectively.

Conclusions

In this real life long-term study of patients in CR, 6 year PFS rates were 73.3% with ICI vs 33.9% with TT and 87.2% vs 64.6 % were alive with ICI and TT respectively. Brain relapses were significantly more frequent in the TT responder group than with ICI.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Caroline Robert.

Funding

Has not received any funding.

Disclosure

C. Boutros: Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: MSD; Financial Interests, Personal, Other, conference fee: Pierre Fabre; Financial Interests, Personal, Other, conference fees: Viatris. E. Routier: Financial Interests, Personal and Institutional, Other, conference fees: BMS, Pierre Fabre; Financial Interests, Personal and Institutional, Other, conference fee: Novartis; Financial Interests, Personal and Institutional, Other, compensation: BMS, Pierre Fabre, Novartis. C. Robert: Financial Interests, Personal and Institutional, Advisory Role: BMS, Pierre Fabre, Novartis, MSD, Roche, Sanofi, AstraZeneca, Merck; Financial Interests, Personal and Institutional, Other, cofounder: Ribonexus. All other authors have declared no conflicts of interest.