93MO - Optimal 18F-FDG PET/CT (FDG-PET) cut-off for pathological complete response (pCR) prediction in HER2-positive [HER2+] early breast cancer (EBC) patients (pts) treated with neoadjuvant trastuzumab (T) and pertuzumab (P) in PHERGain trial

Background

PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy (CT) de-escalation in HER2-positive, stage I-IIIA, invasive, operable breast cancer with at least one breast lesion evaluable by FDG-PET. Based on data from NeoALTTO study, FDG-PET “responders” were defined as those pts with maximum standardized uptake value (SUV_max) reduction of at least 40% in all their target lesions after two cycles of T and P. Of the 285 patients included in T+P arm, 227 pts were FDG-PET responders and received a total of 8 cycles of T+P. pCR, defined as pT0/isN0, reached 37.9% (86/227 pts). Here we describe secondary preplanned analysis of the best cut-off of SUV_max reduction for pCR prediction.

Methods

ROC analysis was applied to research the most appropriate deltaSUV_max cut-off in HER2+ EBC pts treated exclusively with neoadjuvant T and P (± endocrine therapy).

Results

The delta SUV_max capability of predicting pCR in terms of AUC was 72.1% (95%CI, 65.1-79.2). The optimal SUV_max reduction cut-off was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity for prediction of pCR. Yet, using this cut-off, 32.6% (74/227 pts) would be classified as FDG-PET responders increasing the pCR rate from 37.9% (cut-off ≥40%) to 59.5% (44/74 pts) (p<0.01). With this optimized cut-off 19.4% (44/227 pts) would avoid chemotherapy to achieve a pCR. Subgroup analysis in pts with HER2 immunohistochemistry score 3+ will be reported.

Conclusions

Increased deltaSUV_max cut-off (≥77%) after two cycles of exclusive T+P achieves a pCR rate in the range of control arm with CT+TP in PHERGain (59,5% vs. 57,7%, respectively) selecting a subgroup of pts with HER2 addicted tumors. However, the original cut-off (≥40%) maximizes the number of pts who could avoid CT. The definitive value of pCR in the absence of CT should be confirmed by final DDFS results from PHERGain trial.

Legal entity responsible for the study

Medica Scientia Innovation Research (MEDSIR) Barcelona, Spain and Ridgewood, New Jersey.

Funding

Has not received any funding.

Disclosure

G. Gebhart: Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Funding: Roche. M. Keyaerts: Financial Interests, Institutional, Funding, Precirix; Financial Interests, Personal, Stocks/Shares, Abscint. S. Escriva de Romani: Financial interests, Personal, Invited Speaker: Daiichi Sankyo/AstraZeneca, Pfizer, Roche. Financial interests, Personal, Advisory Board: Daiichi Sankyo/AstraZeneca, Roche, Seagen. Financial interests, Insitutional, Other, Local PI: Byondis, Lilly, MedSIR, Roche, Synthon. M.A. Colleoni: Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pfizer, OBI Pharma, Celldex; AstraZeneca; Financial Interest, Personal, Research Grant: Roche. M. Atienza de Frutos: Financial Interests, Personal, Full or part-time Employment: Lilly; Financial Interests, Personal, Stocks/Shares: Lilly. M. Sampayo-Cordero: Financial Interests, Personal, Other: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Advisory Board: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Speaker’s Bureau: MEDSIR, Syntax for Science, Nestle, Roche; Financial Interests, Personal, Funding: MEDSIR, Syntax for Science, Nestle, Roche. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, LEUKO, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Zymeworks, Gemoab, Gilead, Menarini, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires, Roche, Ariad Pharmaceuticals, AstraZeneca, Bayer Healthcare, Eisai, Guardanth Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly; Financial Interests, Personal, Expert Testimony: Eisai. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MEDSIR, Initia-Research; Financial Interests, Personal, Advisory Board: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, Genomic Health, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Institutional, Funding: Roche, Foundation Medicine, Pierre Fabre, Agendia; Financial Interests, Personal, Other: Roche, Lilly, Novartis, Pfizer, AstraZeneca. All other authors have declared no conflicts of interest.