Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial.
The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort.



Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0.



Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline.



In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.
German Breast Group, Neu-Isenburg, , Germany
S
S
Loibl
Department of Obstetrics & Gynecology, Sana Klinikum, Offenbach, Germany.
C
C
Jackisch
National Center for Tumor Diseases, University Hospital, Heidelberg, , Germany.
A
A
Schneeweiss
Breast Cancer Center, Elisabeth Krankenhausx, Weinbergstraße 7, Kassel, Germany.
S
S
Schmatloch
Department of Gynecology & Obstetrics, University Women's Hospital Essen, Essen, Germany.
B
B
Aktas
Department of Pathology, University Hospital Charité, Berlin, Germany.
C
C
Denkert
Gynecology, St. Barbara-Klinik Hamm-Heessen, Hamm, Germany.
H
H
Wiebringhaus
Breast Unit, Interdisziplinäres Brustzentrum an den Kliniken Essen-Mitte, Essen, Germany.
S
S
Kümmel
Breast Unit, Brustzentrum im Krankenhaus Köln-Holweide, Köln, Germany.
M
M
Warm
Women's Clinic, Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Frauenheilkunde, München, Germany.
S
S
Paepke
Oncology, Onkologische Schwerpunktpraxis Bielefeld, Germany.
M
M
Just
Women's Clinic, Klinikum zum Roten Kreuz, München, Germany.
C
C
Hanusch
Breast Unit, Marien Hospital Witten, Witten, Germany.
J
J
Hackmann
Women's Clinic, Klinik für Gynäkologie am Campus Charité Mitte, Berlin, Germany.
J-U
JU
Blohmer
Women's Clinic, Klinikum Mutterhaus der Borromäerinnen, Trier, Germany.
M
M
Clemens
Department of Gynecology, Universitäts-Frauenklinik, Magdeburg, Germany.
S
S
Dan Costa
Women's Clinic, Universitäts-Frauenklinik, Rostock, Germany.
B
B
Gerber
Department of Pathology, Zentrum für Pathologie, Zytologie und Molekularpathologie Neuss, Germany.
K
K
Engels
German Breast Group, Neu-Isenburg, , Germany
V
V
Nekljudova
German Breast Group, Neu-Isenburg, , Germany
G
G
von Minckwitz
Department of Gynecology and Obstetrics, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
M
M
Untch
D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D018943:Anthracyclines / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000068878:Trastuzumab / Q000008:administration & dosage
D000418:Albumins; D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D015251:Epirubicin; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C520255:130-nm albumin-bound paclitaxel; C508053:ERBB2 protein, human; C485206:pertuzumab
early breast cancer; neoadjuvant chemotherapy; pertuzumab; trastuzumab