Trastuzumab deruxtecan has shown efficacy in ABC pts with low HER2 positivity by immunohistochemistry (IHC) and a negative in situ hybridization (ISH), termed H-Low (HER2 1+, or 2+ with negative ISH). A better understanding of this heterogeneous group is needed.
This analysis from RegistEM study (NCT02819882) compares characteristics and outcomes of H-Low and H-0 pts diagnosed with ABC from Jan-16 to Dec-19. With a cut-off 14-Nov-22, and an ongoing database, 1232 HER2- pts were included, 713 H-0 and 519 H-Low (IHC1+ 54%, IHC2+ ISH- 46%). Pts were split in 4 groups based on HER2 and hormone receptor (HR). HER2 and HR were available from a tumor sample obtained before the 1st-line (1L).
Age, gender, race, menopausal status and ABC location (distant metastases and unresectable locally advanced disease) were similar between groups at ABC diagnosis. HER2 expression (accounting H-Low and HER2+) was higher in de novo metastatic vs early BC pts. Distribution according to bone, soft tissue and visceral metastases was similar in HR+ groups; more soft tissue and visceral metastases were reported in HR- groups. No. of metastatic locations was similar in H-0 pts regardless of HR status, but more pts with 2-3 organs involved were observed in the H-Low HR- group. No statistically significant differences were observed in PFS and OS between H-0 and H-Low (even considering IHC1+ and IHC2+ & ISH- separately), regardless of HR status. Looking at primary and metastatic paired tumors, a third of HR+ pts changed from H-0 to H-Low and vice versa, and nearly 50% of HR- pts changed from H-Low to H-0; HER2+ (HR+ or HR-) BC barely changed.
Our results show that H-Low have similar characteristics and outcomes than H-0 BC pts. In HER2- pts, the disease behavior is conditioned by HR status in absence of therapies targeted to H-Low population.
NCT02819882.
GEICAM, Spanish Breast Cancer Group Research.
Roche Farma, S.A.; Novartis Farmacéutica, S.A.; Celgene, S.L. (a BMS company); Pfizer, S.L.U.; AstraZeneca Farmacéutica Spain, S.A. in alliance with Daiichi Sankyo Spain, S.A.U.; Lilly, S.A.U.; Seagen, S.L.U.; Gilead Sciences, S.L.
I. Alvarez Lopez: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Novartis, Roche, Gilead; Financial Interests, Personal, Funding: AstraZeneca, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Meetting travel and inscription expenses: Pfizer, Roche, Eisai, Eli Lilly. A.L. Guerrero Zotano: Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Pierre Fabre, Exact Science Novartis; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer, Novartis, Gilead; Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Exact Science, Pierre Fabre. S. Antolín-Novoa: Financial Interests, Personal, Other, Consulting fees: Gilead. A. Tibau: Financial Interests, Personal, Other, Honoraria: Lilly, Novartis. M. Corbellas Aparicio: Financial Interests, Other, Travel, accommodations, expenses: GSK. J. Cruz Jurado: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Lilly, Glaxo, Eisai, Pierre Fabre, PharmaMar, Daiichi, AstraZeneca, Glaxo, Seagen, Gilead; Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Novartis, Lilly, Glaxo, Eisai, Pierre Fabre, PharmaMar, Daiichi, AstraZeneca, Glaxo, Seagen, Gilead. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Roche, Pfizer, Pierre Fabre, Lilly, Seagen, Daiichi Sankyo, Gilead Sciences, MSD, GlaxoSmithKline, Stemline, Menarini and Veracyte. F. Rojo: Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca, BMS, Daiichi Sankyo, Janssen, Pierre Fabre, Roche, Novartis, Pfizer, Merck. All other authors have declared no conflicts of interest.