Abstract 191P
Background
Predictive biomarkers of response to HER2-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early changes in tumor standardized uptake values corrected for lean body mass (SULmax) on FDG-PET/CT predicted pathologic complete response (pCR) to neoadjuvant trastuzumab and pertuzumab (HP) in HER2-positive breast cancer (PMID:33999652). We hypothesized that early changes on FDG-PET/CT will predict RFS/OS.
Methods
Patients (pts) with stage II/III ER-negative/HER2-positive breast cancer received 4 cycles of neoadjuvant HP (n=88, accrued Jan 2014-Aug 2017); pCR after HP was 22% (18/83). Further neoadjuvant non-study therapy was administered in 28% (25/88). The majority received adjuvant therapy per physician discretion. FDG-PET/CT was performed at baseline and C1D15. Associations between early metabolic response on FDG-PET/CT (≥ 40% decline in SULmax between baseline and C1D15, or C1D15 SULmax value ≤3) and pCR, RFS and OS were summarized using the Kaplan-Meier method, and compared between subgroups using logrank tests. Due to small event numbers, Cox Regressions with likelihood ratio confidence intervals [CI] were used to evaluate covariate effects.
Results
Median follow-up was 53.7 months (83/88 evaluable), with 6 deaths and 14 RFS events. Estimated RFS and OS at 3 years was 84% (95% CI, 76%-92%) and 92% (95% CI, 87%-98%) respectively. D15 SULmax ≤3 (achieved in 57% pts) was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11-1.05; p=0.06) and OS (HR, 0.14, 95% CI, 0.01-0.85; p=0.03). The association of SULmax decline ≥ 40% (achieved in 59%) with RFS/OS did not reach statistical significance. pCR was associated with improved RFS (HR, 0.25; 95% CI, 0.01-1.24; P=0.10), although did not reach statistical significance.
Conclusions
For the first time, we report a potential association between early change in SULmax on FDG-PET/CT and RFS/OS outcomes in pts with ER-negative/HER2-positive breast cancer receiving neoadjuvant HER2-directed therapy. If confirmed this imaging-based biomarker may facilitate early individualization of therapy.
Clinical trial identification
NCT01937117.
Editorial acknowledgement
Legal entity responsible for the study
Translational Breast Cancer Research Consortium.
Funding
TBCRC and its foundation partners (The Breast Cancer Research Foundation and Susan G. Komen for the Cure) ASCO CCF CDA 2013 Genentech (ML28190) SKCCC Core Grant (P30-CA006973) AVON Center of Excellence (01-2017-007) NCI Quantitative Imaging Network (QIN) contract (5U01CA140204) Breakthrough Cancer Research.
Disclosure
J. Leal: Financial Interests, Personal, Advisory Role: PlenaryAI. L. Solnes: Other, Research Grant: Novartis; Other, Consultant: Lantheus; Other, Royalties: Elsevier. V. Abramson: Financial Interests, Advisory Role: Daiichi Sankyo, Novartis, AstraZeneca. L. Carey: Financial Interests, Personal, Royalties, immediate family member-royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme.: Falcon Therapeutics; Financial Interests, Institutional, Funding, research funding: Syndax, Immunomedics, Novartis, Nanostring Technologies, AbbVie, Seattle Genetics, Veracyte; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: sanofi, Novartis, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, AstraZeneca/ Daiichi Sankyo, Apitude Health, Exact Sciences. M.C. Liu: Other, Research Support: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Other, Advisory Board: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. M. Rimawi: Financial Interests, Personal, Advisory Board, Consulting: Genentech, Novartis, AstraZeneca, Seagen; Financial Interests, Personal, Advisory Board, Advisory Board: Macrogenics; Financial Interests, Institutional, Research Grant: Pfizer. J. Specht: Other, Institutional, Other, Research Funding: Merck, Genentech, Xencor, AbbVie, Seattle Genetics, Celcuity, Minerva Biotech, Myriad Pharmaceuticals; Other, Invited Speaker: Daiichi Sankyo, Binaytara Foundation; Other, Advisory Role: GE Healthcare, GlaxoSmithKline. A.M.V. Storniolo: Financial Interests, Personal, Other, DSMB/advisory: AstraZeneca. V. Valero: Financial Interests, Personal, Invited Speaker: Roche. C. Vaklavas: Financial Interests, Institutional, Other, Research Funding: Pfizer, SeaGen, H3 Biomedicine/EISAI, AstraZeneca, CytomX, Genentech, Roche, Pfizer, Incyte, Pharmacyclics, Novartis, TRACON Pharmaceuticals, Innocrin Pharmaceuticals, Zymeworks; Non-Financial Interests, Personal, Advisory Role: Guidepoint, Novartis, SeaGen, Daiichi Sankyo; Other, Personal, Advisory Role, Unpaid consultation: Genentech; Financial Interests, Personal, Invited Speaker, Participation in non-CME activity: Gilead, AstraZeneca; Financial Interests, Personal, Full or part-time Employment, (wife): Flatiron. E. Winer: Other, Consultant Honoraria: Carrick Therapeutics, Genentech/Roche, GSK, Jounce Therapeutics; Other, Honoraria: Genomic Health; Other, Advisory Board, Honoraria: Leap Therapeutics. I. Krop: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Macrogenetics, Taiho Oncology, Genentech/Roche, Seattle Genetics, AstraZeneca; Financial Interests, Personal, Other, DSMC: Novartis, Merck; Financial Interests, Institutional, Other: Roche, Macrogenics, Pfizer. A.C. Wolff: Financial Interests, Institutional, Research Grant, Research funding for a TBCRC trial: Pfizer. A. Cimino-Mathews: Financial Interests, Institutional, Other, Research Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb. R. Wahl: Financial Interests, Personal, Advisory Board: Clarity Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Voximetry; Financial Interests, Institutional, Other, Research contract: Bayer, Siemens; Financial Interests, Institutional, Other, Service contract: White Rabbit AI; Non-Financial Interests, Personal, Member of the Board of Directors: Society of Nuclear Medicine. V. Stearns: Other, Institutional, Research Grant: AbbVie, Biocept, Pfizer, Novartis, Puma Biotechnology; Other, Advisory Board: Novartis; Other, Member of data safety monitoring board: Immunomedics Inc, AstraZeneca; Other, Non-financial support: Foundation Medicine Study Assays. R.M. Connolly: Financial Interests, Institutional, Other, Research Funding: MSD Ireland, Pfizer, Daichii Sankyo, AstraZeneca; Financial Interests, Institutional, Other, Unrestricted Pfizer Education Grant: Pfizer. All other authors have declared no conflicts of interest.