First-line bevacizumab plus paclitaxel in Japanese patients with HER2-negative metastatic breast cancer: subgroup results from the randomized Phase III MERiDiAN trial.
BACKGROUND
In the double-blind placebo-controlled randomized Phase III MERiDiAN trial (ClinicalTrials.gov NCT01663727), adding bevacizumab to paclitaxel for HER2-negative metastatic breast cancer (mBC) significantly improved progression-free survival (PFS; stratified hazard ratio [HR] 0.68, 99% confidence interval [CI], 0.51-0.91). We assessed the efficacy and tolerability of first-line bevacizumab-paclitaxel in the subset of Japanese patients in MERiDiAN.


METHODS
Eligible patients had HER2-negative mBC previously untreated with chemotherapy. Plasma vascular endothelial growth factor (VEGF)-A was measured before randomization to paclitaxel 90 mg/m2 on Days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on Days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were: baseline plasma VEGF-A level, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary endpoints were investigator-assessed PFS in the intent-to-treat (ITT) population and in the subgroup with high plasma VEGF-A. This exploratory analysis evaluated efficacy and safety in the subpopulation treated in Japanese centers.


RESULTS
Of 481 patients randomized in MERiDiAN, 54 (11%) were Japanese. The stratified PFS HR in the Japanese subgroup was 0.64 (95% CI, 0.29-1.40). Median PFS was 9.2 months with placebo-paclitaxel (n = 30) versus 12.7 months with bevacizumab-paclitaxel (n = 24). Bevacizumab was associated with increased incidences of Grade ≥3 neutropenia, peripheral sensory neuropathy and hypertension, but there was no Grade ≥3 proteinuria, bleeding or gastrointestinal perforation.


CONCLUSIONS
Bevacizumab-paclitaxel efficacy in Japanese patients was consistent with the MERiDiAN ITT population. No new safety signals were seen and tolerability was consistent with previous experience.
Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka.
Norikazu
N
Masuda
Department of Breast Surgery, Hokkaido Cancer Center, Sapporo.
Masato
M
Takahashi
Department of Surgery, Shizuoka General Hospital, Shizuoka.
Kazuhiko
K
Nakagami
Departments of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto.
Yasuhiro
Y
Okumura
Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka.
Takahiro
T
Nakayama
Department of Surgery, Niigata Cancer Center Hospital, Niigata.
Nobuaki
N
Sato
Chugai Pharmaceutical Co. Ltd, Tokyo.
Kazumitsu
K
Kanatani
Chugai Pharmaceutical Co. Ltd, Tokyo.
Kosei
K
Tajima
Department of Surgery, Iwate Medical University, Morioka, Japan.
Masahiro
M
Kashiwaba
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D028761:Withholding Treatment
D000068258:Bevacizumab; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A
Japanese; VEGF-A; bevacizumab; metastatic breast cancer