Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: A multicentre, open-label, randomised phase 2 trial

Lam, Siu W.; Groot, S.M. de; Honkoop, Aafke H.; Jager, Agnes; Tije, Albert J. ten; Bos, Monique M.E.M.; Linn, SC; Bosch, Jackie; Kroep, Judith R.; Braun, J. J.; Tinteren, Harm van; Boven, Epie

doi:10.1016/j.ejca.2014.10.008

Cited by 30 publications

(28 citation statements)

References 33 publications

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“…Because only 15% of patients in the BOOG trial had TNBC, no efficacy data were reported for this subset of individuals. However, in the overall population, the median PFS was 11.2 months with the triplet induction regimen followed by the combination regimen of capecitabine and bevacizumab and the ORR was 58% …”

Section: Discussionmentioning

confidence: 99%

“…Recently, results were published from the randomized phase 2 Dutch Breast Cancer Research Group (BOOG) trial evaluating bevacizumab plus weekly paclitaxel with or without capecitabine as first-line therapy for patients with locally recurrent/MBC. 25 The triplet treatment regimen differed from the A-TaXel regimen with respect to the schedule of capecitabine administration (825 mg/m 2 twice daily on days 1-14 vs our weekly schedule) and the paclitaxel dose (90 mg/m 2 vs 80 mg/m 2 in the A-TaXel trial). However, an important similarity was the relatively short paclitaxel exposure (6 cycles of 3 weeks in our study vs 8 cycles of 3weeks in the BOOG trial) followed by maintenance therapy with bevacizumab either alone or combined with capecitabine.…”

Section: Discussionmentioning

confidence: 99%

“…However, in the overall population, the median PFS was 11.2 months with the triplet induction regimen followed by the combination regimen of capecitabine and bevacizumab and the ORR was 58%. 25 An alternative approach to improve tolerability, evaluated in a German randomized phase 3 trial, was to replace the combination regimen of a taxane and capecitabine with a vinorelbine and capecitabine doublet combined with bevacizumab. The PFS was slightly (but not significantly) improved with the addition of vinorelbine to capecitabine plus bevacizumab, with a more pronounced effect observed in patients with TNBC (median PFS, 7.0 months).…”

Section: Discussionmentioning

confidence: 99%

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Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first‐line therapy for triple‐negative, metastatic, or locally advanced breast cancer: Results from the GINECO A‐TaXel phase 2 study

Ferrero

Hardy‐Bessard²,

Capitain³

et al. 2016

Cancer

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BACKGROUND The current study was performed to determine the efficacy and safety of first‐line combination therapy with bevacizumab, paclitaxel, and capecitabine for triple‐negative, locally advanced/metastatic breast cancer (LA/MBC). METHODS Patients with measurable triple‐negative LA/MBC who had received no prior chemotherapy for their disease received 4‐weekly cycles of paclitaxel (80 mg/m2 on days 1, 8, and 15 for up to 6 cycles) combined with capecitabine (800 mg/m2 twice daily on days 1‐5, 8‐12, and 15‐19) and bevacizumab (10 mg/kg on days 1 and 14) repeated every 4 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was the objective response rate; secondary endpoints were progression‐free survival, duration of response, overall survival, and safety. RESULTS Between April 2010 and March 2012, 62 eligible patients were enrolled. The median age of the patients was 57 years, 74% had received adjuvant chemotherapy, and 65% had visceral metastases. Patients received a median of 6 cycles (range, 1‐45 cycles). The objective response rate was 77% (95% confidence interval [95% CI] 66%‐88%), including complete response in 19% of patients. The median duration of response was 5.6 months (range, 1.3‐27.6 months). The median progression‐free survival was 7.6 months (95% CI, 6.3‐9.0 months) and the median overall survival was 19.2 months (95% CI, 17.4‐20.9 months). The most common grade ≥3 adverse events were hypertension (35% of patients) and neutropenia (23% of patients); 5% of patients experienced febrile neutropenia. Grade ≥2 hand‐foot syndrome, alopecia, and nail toxicity each occurred in 40% of patients (adverse events were recorded before every cycle and graded according to Common Terminology Criteria for Adverse Events [version 4.0]). Treatment was interrupted because of toxicity in 22% of patients. CONCLUSIONS A triplet regimen of paclitaxel, capecitabine, and bevacizumab followed by maintenance therapy with capecitabine and bevacizumab demonstrated high activity and manageable safety in this difficult‐to‐treat population. Cancer 2016;122:3119–26. © 2016 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first‐line therapy for triple‐negative, metastatic, or locally advanced breast cancer: Results from the GINECO A‐TaXel phase 2 study

Ferrero

Hardy‐Bessard²,

Capitain³

et al. 2016

Cancer

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“…Study details and clinical findings have been described in detail in ref. (15 , and capecitabine (825 mg/kg orally twice daily on days 1-14) every 3 weeks for 8 cycles, followed by the same dose of bevacizumab and capecitabine every 3 weeks afterwards (ATX). Treatment was continued until disease progression, unmanageable toxicities or withdrawal of consent.…”

Section: Patients and Study Designmentioning

confidence: 99%

Angiogenesis- and Hypoxia-Associated Proteins as Early Indicators of the Outcome in Patients with Metastatic Breast Cancer Given First-Line Bevacizumab-Based Therapy

Lam

Nota

Jager³

et al. 2016

Clinical Cancer Research

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Purpose: We examined whether pretreatment levels of angiogenesis-or hypoxia-related proteins and their changes after one cycle of first-line bevacizumab-based therapy were associated with response, PFS, or OS in patients with metastatic breast cancer.Experimental Design: We included 181 patients enrolled in the phase II ATX trial evaluating first-line paclitaxel and bevacizumab without or with capecitabine (NTR1348). Plasma samples were analyzed for VEGF-A, soluble VEGFR2 (sVEGFR2), angiopoietin 2 (ANG2), soluble TIE2 (sTIE2), IL6, IL8, and carbonic anhydrase 9 (CA9). Baseline serum CA15-3 was documented. HR was adjusted for confounding factors. Where appropriate, an optimal cut-off value defining a high and a low group was determined with Martingale residuals.Results: At baseline, multiple proteins were significantly associated with PFS (ANG2, IL6, IL8, CA9, CA15-3) and OS (ANG2, sTIE2, IL6, IL8, CA9, CA15-3). After one cycle, VEGF-A, ANG2, sTIE2, and IL8 significantly decreased, while sVEGFR2 and CA9 significantly increased. The relative change in sVEGFR2 (P ¼ 0.01) and IL8 (P ¼ 0.001) was associated with response. Defining optimal cut-off, patients with a high CA9 rise (>2.9%) had better PFS (HR 0.45) and OS (HR 0.54) than those with low/no rise.Conclusions: Multiple angiogenesis-or hypoxia-related proteins were prognostic for PFS and OS. Molecular agents targeting these proteins might be beneficial in patients with high levels. Changes in IL8 or sVEGFR2 levels at second cycle appear predictive for response. Changes in CA9 levels during bevacizumabbased therapy for prediction of PFS and OS merit further study.

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“…The study population included 188 women with HER2-negative MBC, who were previously enroled in the multicenter, randomised, phase II ATX trial (BOOG2006-06; EudraCT number 2006-006058-83) (Lam et al , 2014). Pharmacogenetic analysis, a preplanned part of the original trial design, was approved by the institutional review board of all participating hospitals and was conducted in accordance with the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients

Lam¹,

Frederiks

Straaten

et al. 2016

Br J Cancer

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Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: A multicentre, open-label, randomised phase 2 trial

Cited by 30 publications

References 33 publications

Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first‐line therapy for triple‐negative, metastatic, or locally advanced breast cancer: Results from the GINECO A‐TaXel phase 2 study

Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first‐line therapy for triple‐negative, metastatic, or locally advanced breast cancer: Results from the GINECO A‐TaXel phase 2 study

Angiogenesis- and Hypoxia-Associated Proteins as Early Indicators of the Outcome in Patients with Metastatic Breast Cancer Given First-Line Bevacizumab-Based Therapy

Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients

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