Abstract 412P
Background
The phase 3 TROPiCS-02 study demonstrated clinically meaningful improvement on survival outcomes associated with SG, a Trop-2–directed antibody-drug conjugate, over chemotherapy in pretreated HR+/HER2- mBC. We describe an exploratory analysis into the prognostic and predictive value of ctDNA.
Methods
Patients (pts) were randomized 1:1 to receive SG or chemotherapy until disease progression or unacceptable toxicity. Longitudinal plasma samples were collected at baseline (BSL) and cycle 2 day 1 (C2D1) and tested using Infinity RUO ctDNA panel. ctDNA molecular response (MR) was calculated as the ratio of C2D1 mean variant allele fraction (mVAF) to BSL mVAF to reflect on-treatment ctDNA changes and clinical outcomes were correlated with ctDNA.
Results
Of 543 pts in the intent-to-treat (ITT) population, 210 (39%) had ctDNA MR data available with BSL and C2D1 visits. BSL ctDNA mVAF levels were prognostic; the below median BSL mVAF subgroup showed improved mPFS and mOS in both SG and TPC arms (Table). Longitudinal ctDNA from BSL to C2D1 show decreased mVAF in both SG and TPC arms (median reduction of 64% and 56%, respectively). Percent change of mVAF correlated with best overall response (BOR). Pts with partial response (PR) had the largest decrease; pts with progressive disease (PD) had the smallest. Percent change of mVAF was associated with survival outcomes. Pts with a ≥ 50% ctDNA reduction had significantly longer PFS and OS than pts who had <50% ctDNA reduction from BSL to C2D1 (Table).
Conclusions
BSL ctDNA mVAF and changes from BSL to C2D1 were associated with survival outcomes and BOR in both treatment arms. Pts with below median BSL mVAF and >=50% reduction have the best outcome. Benefit with SG over TPC was observed regardless of ctDNA BSL or changes. Our findings contribute to the understanding of ctDNA as an early surrogate marker for long term outcomes in HR+/HER2- mBC pts. Table: 412P
| Efficacy | BSL mVAF | Changes from BSL -C2D1 | ||||||
| TPC (n=97) | SG (n=113) | TPC (n=97) | SG (n=113) | |||||
Clinical trial identificationNCT03901339. Editorial acknowledgementLegal entity responsible for the studyGilead Sciences, Inc. FundingGilead Sciences, Inc. DisclosureH.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc.; Financial Interests, Institutional, Coordinating PI: OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. Y. Zhang: Financial Interests, Personal, Full or part-time Employment, I'm a full time employee at Gilead Sciences: Gilead Sciences; Financial Interests, Personal, Stocks/Shares, I hold stocks from Gilead Sciences: Gilead Sciences; Financial Interests, Personal, Stocks/Shares, I hold stocks from Allogene therpeutics: Allogene Therapeutics. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Stemline Menarini; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Pfizer, Roche, Gilead, Eisai, MSD, Seagen, Lilly; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Roche. J. Cortés: Financial Interests, Personal, Advisory Board, consulting/advisor: Roche, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Lilly, MERCK SHARP& DOHME, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo, Astrazeneca, Gilead, Steamline Therapeutics; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, Astrazeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Queen Mary University of London, Iqvia; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, Astrazeneca, Steamline Therapeutics; Other, travel cost and expenses: Merck Sharp&Dhome. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: ARC Therapeutics, Daichii Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, Seagen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma, Hengrui USA; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Sumitovant Biopharmaceuticals, OncXerna, Umoja Biopharma, Zentalis, Natera; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol-Myers Squibb; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory board/consulting: Jazz Pharma; Financial Interests, Personal, Advisory Board: Tango Therapeutics, Systimmune, eFFECTOR, Cullinan Oncology, Arvinas; Financial Interests, Institutional, Funding, And steering committing: AstraZeneca; Financial Interests, Institutional, Funding, And steering committee: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Bristol Myers Squibb, Eisai, Merck, Novartis; Financial Interests, Personal and Institutional, Steering Committee Member: CytomX; Financial Interests, Institutional, Funding, and steering committee: Gilead, Genentech/Roche; Financial Interests, Institutional, Local PI: Stemline/Menarini. S. Tang: Financial Interests, Institutional, Full or part-time Employment, Working as a bioinformatics research scientist in Gilead Sciences: Gilead Sciences, Inc.; Financial Interests, Institutional, Stocks/Shares: Gilead Sciences, Inc. O.K. Yoon: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences; Financial Interests, Personal, Stocks/Shares: Gilead Sciences. W. Verret: Financial Interests, Institutional, Full or part-time Employment, I am a paid employee of Gilead Sciences: Gilead Sciences. M. Das Thakur: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences; Financial Interests, Institutional, Stocks/Shares: Gilead Sciences; Financial Interests, Institutional, Funding: Gilead Sciences; Non-Financial Interests, Project Lead: Gilead Sciences. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Coordinating PI: Genentech, Novartis, Pfizer, Merck, Sanofi, Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly, Menarini; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. 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