5058 Bevacizumab (Bev) combined with either capecitabine (X) or weekly paclitaxel (Pac) as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer (LR/MBC): the CECOG phase III TURANDOT trial

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m2 followed 24 hours later by paclitaxel 220 mg/m2) or FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non–anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P = .032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P = .034]; overall survival 23.3 months v 18.3 months [P = .013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P < .001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

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Trebananib (AMG 386) plus weekly paclitaxel with or without bevacizumab as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer: A phase 2 randomized study

The Breast ◽

10.1016/j.breast.2014.11.003 ◽

2015 ◽

Vol 24 (3) ◽

pp. 182-190 ◽

Cited By ~ 32

Author(s):

Véronique Diéras ◽

Hans Wildiers ◽

Jacek Jassem ◽

Luc Y. Dirix ◽

Jean-Paul Guastalla ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Randomized Study ◽

Metastatic Breast ◽

Phase 2 ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Amg 386 ◽

Locally Recurrent

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Phase III study of taxane chemotherapy with lapatinib or trastuzumab as first-line therapy for women with HER2/neu-positive metastatic breast cancer (BC) (NCIC Clinical Trials Group (NCICCTG)MA.31/GSK EGF 108919).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.tps108 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. TPS108-TPS108 ◽

Cited By ~ 3

Author(s):

W. Parulekar ◽

J. W. Chapman ◽

S. Aparicio ◽

Y. Murray ◽

F. M. Boyle ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Phase Iii ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Phase Iii Study ◽

Taxane Chemotherapy

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Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.18_suppl.lba671 ◽

2012 ◽

Vol 30 (18_suppl) ◽

pp. LBA671-LBA671 ◽

Cited By ~ 35

Author(s):

Karen A. Gelmon ◽

Frances Boyle ◽

Bella Kaufman ◽

David Huntsman ◽

Alexey Manikhas ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Phase Iii ◽

Rank Test ◽

Her2 Status ◽

P Value ◽

First Line ◽

First Line Therapy ◽

Line Therapy

LBA671 Background: The relative efficacy of L vs T when combined with Tax chemotherapy in the first-line setting of metastatic breast cancer (BC) is unknown. Methods: MA.31 compares Tax-based therapy, paclitaxel 80mg/m2 wkly or docetaxel 75mg/m2 3 wkly for 24 wks in combination with L or T. The L dose was 1,250 mg po daily with Tax followed by 1,500 mg daily (LTax/L). After a loading dose, the T dose was 2 mg/kg wkly or 6 mg/kg 3 wkly + Tax followed by T 6 mg/kg 3 wkly (TTax/T). Stratification was by prior neo/adjuvant HER2 therapy, prior neo/adjuvant Tax, planned Tax (paclitaxel vs docetaxel), and liver metastases. The primary endpoint is ITT progression-free survival (PFS), defined as time from randomization to objective progressive disease based on RECIST criteria or death from any cause. The protocol-specified IA was performed after observing 333 PFS events; the trial was to stop if the 2-sided p-value from the stratified log-rank test was less than 0.03. The NCIC CTG’s independent DSMC reviewed IA results and recommended disclosure because the superiority boundary was crossed. A secondary analysis utilized central laboratory-confirmed HER2 + status. Results: Between July 17 2008 and Dec 1 2011, 652 pts were accrued. Data from 636 pts (525 HER2 centrally confirmed) were included in the IA with clinical cutoff date of Nov 7 2011 and database lock of Apr 13 2012. Median follow-up was 13.6 mos, 12.9 mos for LTax/L pts and 14.0 mos for TTax/T patients. In the ITT analysis, PFS was inferior with LTax/L compared to TTax/T hazard ratio (HR) =1.33; 95% CI 1.06-1.67; p=0.01. LTax/L had median PFS 8.8 mos (95% CI 8.3-10.6) compared to TTax/T 11.4 mos (95% CI 10.8-13.7). PFS in the centrally confirmed HER2+ had HR 1.48 (95%CI 1.15-1.92; p=0.003) (LTax/L to TTax/T). No difference in overall survival was detected (LTax/L to TTax/T) HR= 1.1 (95% CI 0.75-1.61; p=0.62). More grade 3-4 diarrhea and rash was observed with LTax/L (p<0.001). Conclusions: LTax/L therapy is associated with a shorter PFS compared to TTax/T as first line therapy for HER2+ metastatic BC. ClinicalTrials.gov: NCT00667251. CCSRI grant: 021039. Supported by GlaxoSmithKline.

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