A randomized phase 2 study exploring the role of bevacizumab and a chemotherapy-free approach in HER2-positive metastatic breast cancer: The HAT study (BOOG 2008-2003), a Dutch Breast Cancer Research Group trial.
BACKGROUND
To explore the role of bevacizumab and a chemotherapy-free approach, the authors evaluated the combination of bevacizumab, trastuzumab, and paclitaxel (HAT) and the regimen of trastuzumab and bevacizumab (HA) with the addition of paclitaxel after progression (HA-HAT) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.


METHODS
In a noncomparative phase 2 trial, patients were randomized between HAT and HA-HAT. The primary endpoint was the progression-free rate at 1 year (1-year PFR). In the HA-HAT group, progression-free survival (PFS) was separately established for HA (PFS1) and HAT (PFS2).


RESULTS
Eighty-four patients received HAT (n = 39) or HA-HAT (n = 45). The 1-year PFR was 74.4% (95% confidence interval [CI], 61.8%-89.4%) and 62.2% (95% CI, 49.6%-89.4%) in the HAT and HA-HAT arms, respectively. The median PFS was 19.8 months (95% CI, 14.9-25.6 months) in the HAT arm and 19.6 months (95% CI, 12.0-32.0 months) in the HA-HAT arm. In the HA-HAT arm, the median PFS1 was 10.4 months (95% CI, 6.2-15.0 months), and the median PFS2 was 8.2 months (95% CI, 7.0-12.6 months). The number and severity of adverse events were comparable between the arms.


CONCLUSIONS
Both HAT and HA-HAT have promising activity in patients with HER2-positive metastatic breast cancer. In particular, starting with only targeted agents and delaying chemotherapy is worth further exploration. Cancer 2016;122:2961-2970. © 2016 American Cancer Society.
Department of Medical Oncology, Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Rotterdam, the Netherlands. j.drooger@ikazia.nl.|Department of Medical Oncology, Ikazia Hospital, Rotterdam, the Netherlands. j.drooger@ikazia.nl.
Jan C
JC
Drooger
Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Harm
H
van Tinteren
Comprehensive Cancer Center of the Netherlands, Amsterdam, the Netherlands.
Steffen M
SM
de Groot
Department of Medical Oncology, Amphia Hospital, Breda, the Netherlands.
Albert J
AJ
Ten Tije
Department of Medical Oncology, Leeuwarden Medical Center, Leeuwarden, the Netherlands.
Hiltje
H
de Graaf
Department of Medical Oncology, Haga Hospital, the Hague, the Netherlands.
Johanneke E A
JE
Portielje
Department of Medical Oncology, Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Rotterdam, the Netherlands.
Agnes
A
Jager
Department of Medical Oncology, Isala Clinic, Zwolle, the Netherlands.
Aafke
A
Honkoop
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Sabine C
SC
Linn
Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Judith R
JR
Kroep
Department of Medical Oncology, Orbis Medical Center, Sittard, the Netherlands.
Frans L G
FL
Erdkamp
Department of Medical Oncology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
Paul
P
Hamberg
Department of Medical Oncology, Deventer Hospital, Deventer, the Netherlands.
Alex L T
AL
Imholz
Department of Medical, Oncology, Vlietland Hospital, Schiedam, the Netherlands.
Quirine C
QC
van Rossum-Schornagel
Department of Medical Oncology, Amphia Hospital, Breda, the Netherlands.
Joan B
JB
Heijns
Dutch Breast Cancer Research Group, Amsterdam, the Netherlands.
A Elise
AE
van Leeuwen-Stok
Department of Medical Oncology, Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Rotterdam, the Netherlands.
Stefan
S
Sleijfer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D000068878:Trastuzumab / Q000008:administration & dosage
D000068258:Bevacizumab; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
bevacizumab; human epidermal growth factor receptor 2; metastatic breast cancer; paclitaxel; trastuzumab