Abstract 246P
Background
Molecular Tumor Boards (MTBs) foster access to biomarker-based anticancer therapies and improve outcomes in patients (pts) with actionable genetic alterations. The effectiveness of MTBs in the management of metastatic breast cancer (mBC) remains to be proven.
Methods
Clinical and genomic data of consecutive pts with mBCs referred to the IEO MTB were reviewed. Genetic alterations were classified by ESCAT. Outcomes of pts showing actionable alterations and receiving molecular-matched therapy (MMT) were compared to those receiving standard therapy (ST). Real-world progression-free survival (rwPFS) and overall survival (OS) were assessed by Kaplan-Meier method and Cox models
Results
From Aug 2019 to Dec 2023, 96 pts with mBC were discussed: 58 hormone receptor-positive (HR+), 37 triple-negative BC (TNBC) and 1 HER2+ cases. After MTB, genetic counseling was performed in 26/96 (27%) pts, while additional molecular analyses were requested in 24/96 (25%); 74 pts (77%) displayed at least one actionable alteration for whom a MMT was recommended. For pts with available follow-up (n=50), 32 (64%) received MMTs, including agents targeting biallelic inactivation of HRD genes (n=27), ERBB2 mutations (n=2), NF1 deletion (n=1), PIK3CAmutation (n=1) and TMB-high (n=1). Pts in the MMT group had a numerically higher proportion of TNBCs (45% vs 35%), brain (18% vs 6%) and liver (64% vs 41%) metastases. The median number of previous therapies was 4 (range 1-15) for both groups. At a median follow-up of 14.4 months (range 2.5-not estimable (NE)), no difference in median rwPFS and 12-month OS rate was observed between the MMT and ST groups (4.1 [95%CI 2.1-8.3] vs 3.1 months [95% CI 1.5-NE], P=0.8; 58% [95%CI 43-78] vs 57% [95%CI 34-97), P=0.9). Pts who received a MMT according to ESCAT I had longer rwPFS (25/32, 5.8 months [95%CI 3.1-8.4]) compared to those with ESCAT II (3/32, 2.1 months [95%CI 1.6-NE]) and ESCAT III (4/32, 2.1 months [95%CI 2-NE]; P=0.09). Median growth modulation index in pts receiving MMT was 0.69, with 24% of pts showing a PFS2/PFS1 ratio >1.3
Conclusions
MTB can provide additional treatment opportunities for pts with mBC, with higher ESCAT Tiers yielding the greatest clinical benefit. MTBs also has utility to identify cases for additional genetic counseling and molecular analyses
Legal entity responsible for the study
European Institute of Oncology.
Funding
Has not received any funding.
Disclosure
A. Marra: Financial Interests, Personal, Advisory Board: Menarini/Stemline; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Travel Support: AstraZeneca. M. Repetto: Financial Interests, Personal, Other, Travel Support: Sanofi. M. Barberis: Financial Interests, Personal, Advisory Role: MSD Oncology, Roche/Genentech, AstraZeneca, GSK, Thermofisher Scientifics, Illumina. N. Fusco: Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme (MSD), AstraZeneca, Daiichi Sankyo, GSK, Gilead, Novartis, Roche, Menarini, Lilly, Sysmex; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme (MSD), AstraZeneca, Menarini; Financial Interests, Personal and Institutional, Research Grant: Novartis, Sysmex, Veracyte. D. Trapani: Other, EMA Healthcare Professional Working Party (HCPWP), member: European Medicines Agency (EMA); Other, EML Cancer Medicines Working Group (CMWG), member: World Health Organization (WHO); Other, Strategic Advisory Group of Experts on In Vitro Diagnostics (SAGE IVD), chair: World Health Organization (WHO). C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. E. Guerini Rocco: Financial Interests, Personal, Invited Speaker: AstraZeneca, AstraZeneca, Exact Sciences, GSK, Illumina, Novartis, Roche, Thermo Fisher Scientific; Financial Interests, Personal, Other, travel accommodation and expenses: AstraZeneca, Exact Sciences, GSK, Illumina, Novartis, Roche, Thermo Fisher Scientific; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Novartis, Roche; Financial Interests, Institutional, Funding: AstraZeneca, GSK; Financial Interests, Personal and Institutional, Research Grant: Thermo Fisher Scientific; Non-Financial Interests, Institutional, Product Samples: Thermo Fisher Scientific, Illumina, Agilent Technologies, Diatech Pharmacogenetics S.r.l., Biocartis. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO; Non-Financial Interests, Member of Board of Directors, Chair of Clinical Practice Guidelines Committee: ESMO. All other authors have declared no conflicts of interest.