Abstract 1042P
Background
Pts with V600BRAF mutant MM have numerically higher rates of progression-free survival (PFS) and overall survival (OS) with 1st line IPI+PD1 vs PD1. Whether this is also true after BRAF/MEKi therapy is yet to be determined. We aimed to: (1) determine the efficacy and safety of PD1 vs IPI+PD1 after BRAF/MEKi; and (2) identify the subgroup of pts with >3 yrs OS with PD1+/-IPI after BRAF/MEKi.
Methods
MM pts treated with BRAF/MEKi who had subsequent PD1 or IPI+PD1 at 8 melanoma centres were included. The endpoints were objective response rate (ORR), PFS, OS & safety for PD1 vs IPI+PD1. Multivariate analysis (MVA) and backward elimination technique were used to build models to predict those pts with OS > 3 yrs with PD1+/-IPI after BRAF/MEKi.
Results
Of 200 MM pts treated with BRAF/MEKi, 115 (57%) had subsequent PD1 and 85 (43%) had IPI+PD1. Differences in baseline characteristics for PD1 vs IPI+PD1 included med. age (63 vs 54 yrs), ECOG PS >= 1 (62% vs 44%), time between BRAF/MEKi and PD1+/-IPI (0.5 vs 0.1 mo), M1C/M1D stage (72% vs 94%) and brain metastases (mets) (38% vs 65%). Med. follow-up from start of IPI+/-PD1 was 37.8 mo (CI 95% 33.9 – 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p>0.05). PFS rate at 1 yr was 34%; 33% with PD1 vs 34% with IPI+PD1 (med PFS 3.8 vs 4.2 mo, p>0.05). OS rate at 1 yr was 55%; 53% with PD1 vs 58% with IPI+PD1 (med OS 14.4 vs 20.5 mo, p>0.05). >=G3 toxicity was higher with IPI+PD1 (31%) vs PD1 (8%) (p<0.05). On MVA, ECOG PS=0 & >=G3 toxicity were associated with higher ORR. ECOG PS=0, elective BRAF/MEKi cessation & absence of liver metastases were associated with longer PFS and OS. OS was significantly longer with IPI+PD1 vs PD1 in non-V600E mutations (80% vs 51%), but no difference in V600E mutations (53% vs 53%). PFS and OS were numerically longer with IPI+PD1 vs PD1 across all other subgroups except for OS in females & III/M1A/M1B stages. 22% of pts had OS >3 yrs with PD1+/-IPI after BRAF/MEKi; the combination of ECOG PS=0, absence of liver metastases and normal LDH identify these pts (AUC=0.82).
Conclusions
IPI+PD1 appears superior to PD1 after BRAF/MEKi in most subgroups of pts, although is more toxic. A combination of clinical factors can accurately identify pts with >3 yrs OS with PD1+/-IPI after BRAF/MEKi.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Melanoma Institute Australia.
Funding
Has not received any funding.
Disclosure
I. Pires da Silva: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Travel Support: BMS; Financial Interests, Personal, Other, Travel Support: Roche. C. Allayous: Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Personal, Other, travel support: BMS ; Financial Interests, Personal, Other, travel support: Amgen. L. Zimmer: Financial Interests, Personal, Other, honoraria: Roche; Financial Interests, Personal, Other, honoraria: BMS ; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Other, honoraria: Pierre Fabre; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Sunpharma; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Travel support: BMS; Financial Interests, Personal, Other, Travel support: Pierre Fabre; Financial Interests, Personal, Other, Travel support: Sanofi; Financial Interests, Personal, Other, Travel support: Amgen; Financial Interests, Personal, Other, Travel support: Novartis; Financial Interests, Personal, Other, Travel support: Sunpharma. O.A. Michielin: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Pierre-Fabre; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Research Grant: Amgen. C. Lebbe: Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Other, honoraria: Amgen; Financial Interests, Personal, Other, honoraria: Avantis Medical Systems; Financial Interests, Personal, Other, honoraria: Pierre Fabre; Financial Interests, Personal, Other, honoraria: Pfizer; Financial Interests, Personal, Other, honoraria: Incyte; Financial Interests, Personal, Other, honoraria: Merck Serono; Financial Interests, Personal, Other, honoraria: Sanofi. J. Mangana: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers and Squibb ; Financial Interests, Personal, Advisory Board: Pierre Fabre ; Financial Interests, Personal, Other, travel support : Ultrasun; Financial Interests, Personal, Other, travel support : L’ oreal; Financial Interests, Personal, Other, travel support : Merck Sharp & Dohme; Financial Interests, Personal, Other, travel support : Bristol Myers and Squibb ; Financial Interests, Personal, Other, travel support : Pierre Fabre . P.A. Ascierto: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche-Genentech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Array; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Medimmune; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Syndax; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Idera; Financial Interests, Personal, Advisory Board: Ultimovacs; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Italfarmaco; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: Nouscom; Financial Interests, Personal, Advisory Board: Takis; Financial Interests, Personal, Advisory Board: Lunaphore; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Roche-Genentech; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal, Other, travel support : MSD. D. Johnson: Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Catalyst Biopharma; Financial Interests, Personal, Advisory Board: Iovance; Financial Interests, Personal, Advisory Board: Jansen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Research Grant: Bristol-Myers Squibb ; Financial Interests, Personal and Institutional, Research Grant: Incyte; Financial Interests, Personal, Advisory Board: Oncosec. M. Carlino: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Ideaya; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Qbiotics; Financial Interests, Personal, Other, honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Other, honoraria: Novartis. A.M. Menzies: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre-Fabre ; Financial Interests, Personal, Advisory Board: QBiotics. G.V. Long: Financial Interests, Personal, Advisory Board: Aduro Biotech Inc; Financial Interests, Personal, Advisory Board: Amgen Inc; Financial Interests, Personal, Advisory Board: Array Biopharma inc; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim International GmbH; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Highlight Therapeutics S.L; Financial Interests, Personal, Advisory Board: Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Board: Novartis Pharma AG; Financial Interests, Personal, Advisory Board: QBiotics Group Limited; Financial Interests, Personal, Advisory Board: Regeneron Pharmaceuticals Inc. All other authors have declared no conflicts of interest.