Norikazu Masuda1, Masato Takahashi2, Kazuhiko Nakagami3, Yasuhiro Okumura4, Takahiro Nakayama5, Nobuaki Sato6, Kazumitsu Kanatani7, Kosei Tajima7, Masahiro Kashiwaba8. 1. Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka. 2. Department of Breast Surgery, Hokkaido Cancer Center, Sapporo. 3. Department of Surgery, Shizuoka General Hospital, Shizuoka. 4. Departments of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto. 5. Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka. 6. Department of Surgery, Niigata Cancer Center Hospital, Niigata. 7. Chugai Pharmaceutical Co. Ltd, Tokyo. 8. Department of Surgery, Iwate Medical University, Morioka, Japan.
Abstract
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.
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.
Authors: Laura Pizzuti; Domenico Sergi; Isabella Sperduti; Luigi Di Lauro; Marco Mazzotta; Claudio Botti; Fiorentino Izzo; Luca Marchetti; Silverio Tomao; Paolo Marchetti; Clara Natoli; Antonino Grassadonia; Teresa Gamucci; Lucia Mentuccia; Emanuela Magnolfi; Angela Vaccaro; Alessandra Cassano; Ernesto Rossi; Andrea Botticelli; Valentina Sini; Maria G Sarobba; Maria Agnese Fabbri; Luca Moscetti; Antonio Astone; Andrea Michelotti; Claudia De Angelis; Ilaria Bertolini; Francesco Angelini; Gennaro Ciliberto; Marcello Maugeri-Saccà; Antonio Giordano; Maddalena Barba; Patrizia Vici Journal: Cancer Biol Ther Date: 2018-02-16 Impact factor: 4.742