Abstract 169P
Background
Deep genomic sequencing aids understanding tumor biology and personalized therapy. The Breast Cancer Unit at Institut Català d'Oncologia l'Hospitalet in collaboration with Vall d'Hebron Institute of Oncology initiated a molecular pre-screening program in 2017. Our goal was to assess the clinical utility of the program and to facilitate patient access to genome-driven cancer therapy (GDT).
Methods
We used AMPLICON or VHIO-Card-300-v4 sequencing to analyse genomic profiles, CNA (NANOSTRING_FUSION), and tumor mutational burden (TMB) in FFPE tumor samples in patients (pts) with ABC. Eligibility criteria included age 18-79, PS ≤1, preserved organ function and preferable hormone receptor-positive (HR+)/HER2-neg subtype. Observational analysis included pts characteristics, tumor mutations (mut) or alterations, use of GDT and survival outcomes.
Results
Between December 2017 and March 2023, successful tumor sequencing was achieved in 232 of 273 pts (84.98%). Median age was 55 (27-79); pts received a median of 1 prior lines (1-5), and most tumors were HR+/HER2- (91.4%). The tumor samples were from primary breast tumors (46.7%) or metastatic sites (53.3%). Median follow-up was 21 months. Somatic mut were identified in 192 pts (83.13%), mostly in: PIK3CA (38.3%), TP53 (15,5%), FGFR (12.2%), ESR1 (11.8%), PTEN (5.4%), BRCA2 (5.4%), AKT (3,6%), ERBB2 (3,6%) and BRCA1 (2.2%). TMB high was found in 8 pts (6,6%). Long-term survivors n=63 (≥5 years since metastasis diagnosis) were associated with fewer TP53 mut (93,7 vs 73,4%; p=0.06) and with no common mut (17,2 vs 28,6%; p=0.06). Among pts treated with CDK 4/6 inhibitors, 112 (66.6%) progressed in ≤24 months, there were more FGFR1 gains (22.4 vs 7.3%; p=0.007) CDKN2A loss (5.2% vs 0%; p=0.017) and a non-significant increase in ESR1 mut (10.9 vs 17.2%; p=0.336). Only 11% of pts received GDT.
Conclusions
We have demonstrated that molecular pre-screening is feasible in the management of ABC, and the somatic mutations identified are consistent with the existing literature. The potential of GDT is clear, and with increased funding for targeted drugs, its benefits will be fully realized.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
Institut Catala d’Oncologia L’Hospitalet.
Funding
Institut Catala d’Oncologia and Vall d’Hebron Institut d’Oncologia.
Disclosure
D. Lluís Garulo: Financial Interests, Personal, Training: Novartis.A.C. Vethencourt Casado: Financial Interests, Personal, Invited Speaker, Presentation in clinical or research sessions as a speaker: Novartis, Eisai; Non-Financial Interests, Personal, Project Lead, GEICAM Grant “Balil-Pelegrí” 2021-2022, sponsored by the Spanish breast cancer research group: GEICAM; Non-Financial Interests, Personal, Affiliate: SOLTI; Non-Financial Interests, Personal, Leadership Role, Participation in the TransGEICAM group, which is part of the Spanish breast cancer research group GEICAM (Not Paid): GEICAM; Other, Personal, Other, Travel, Accommodations, Support for attending meetings: Pfizer, Lilly, Novartis, Roche. A. Stradella: Financial Interests, Personal, Advisory Board, Advisory about CAPITELLO 291 trial: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory on new activities for residents: Novartis; Financial Interests, Personal, Invited Speaker, Trastu-Deruxtecan clinical case meeting: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, meeting on new data on cyclin inhibitors: Novartis. R. Villanueva Vazquez: Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Congress attendance registration: Pfizer, Novartis, Eisai. M.A. Bergamino: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Funding, Travel funding for congress: Novartis; Financial Interests, Personal, Funding, Travel funding for congresses: Eisai. B. Fullana Grimalt: Financial Interests, Personal, Invited Speaker, Invited Speaker: Eisai. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Myers Squibb, Roche, Incyte. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann-La Roche Ltd., Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Pharma, Sanofi-Aventis, Seagen, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Innoup, Millennium; Financial Interests, Personal, Other, SC: Byondis B.V., Glaxo, Macrogenics, Menarini, Merus, Synthon Biopharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GSK, Menarini Ricerche, Immunomedics, Innoup Pharma, Macrogenics, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Personal, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Personal, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). M.J. Gil: Financial Interests, Personal, Advisory Role: Novartis, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Pfizer, Daiichi Sankyo, Roche, Guardant, Lilly. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca, Daiichi Sankyo, Pierre Fabre, Pfizer; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi Sankyo; Non-Financial Interests, Personal, Member of Board of Directors: SOLTI. All other authors have declared no conflicts of interest.
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