Randomized phase II trial of weekly vs. every 2 weeks vs. every 3 weeks nanoparticle albumin-bound paclitaxel with bevacizumab as first-line chemotherapy for metastatic breast cancer Journal Article
| Authors: | Seidman, A. D.; Conlin, A. K.; Bach, A.; Moynahan, M. E.; Lake, D.; Forero, A.; Wright, G. S.; Hackney, M. H.; Clawson, A.; Norton, L.; Hudis, C. A. |
| Article Title: | Randomized phase II trial of weekly vs. every 2 weeks vs. every 3 weeks nanoparticle albumin-bound paclitaxel with bevacizumab as first-line chemotherapy for metastatic breast cancer |
| Abstract: | This randomized phase II trial tested nanoparticle albumin-bound paclitaxel (nab-P) in 3 different schedules: weekly, every 2 weeks (q2W), and every 3 weeks (q3W). Because bevacizumab prolonged progression-free survival in earlier trials with taxanes in metastatic breast cancer (MBC), all the patients received this agent. Weekly nanoparticle albumin-bound paclitaxel (nab-P) appeared to have the highest therapeutic index, but treatment was limited by sensory neuropathy. Background: Nanoparticle albumin-bound paclitaxel (nab-P) and bevacizumab have each demonstrated efficacy in patients with MBC. This trial was designed to further develop nab-P by evaluating its efficacy and safety using every 3 weeks (q3w), every 2 weeks (q2w), or weekly scheduling in combination with bevacizumab as first-line treatment of MBC. Patients and Methods: This open-label phase II study randomized patients to nab-P 260 mg/m2 q3w (arm A) vs. 260 mg/m2 q2w with filgrastim (arm B) vs. 130 mg/m2 weekly uninterrupted, all with bevacizumab (15 mg/kg q3w arm A, 10 mg/kg q2w arms B and C). The primary endpoints were overall response rate (ORR) and toxicity. Time to tumor progression (TTP) and overall survival were secondary endpoints. Results: Of 212 patients randomized, 208 (arm A, 75; arm B, 54; arm C, 79) were treated. Arm B was closed early due to toxicity, with more grade > 2 fatigue (arm A, 46%; arm B, 62%; arm C, 62%) and bone pain (arm A, 11%; arm B, 23%; arm C, 5%). Neurotoxicity grade > 2 was equivalent across the arms (> 50%) and reversible for most patients. Febrile neutropenia occurred in < 3% of patients in all arms. ORR was similar among the arms (arm A, 45%; arm B, 41%; arm C, 46%). Median TTP was slightly longer in arm C (9.0 months) vs. arms A (8.0 months) and B (5.8 months) (overall, P =.105). Conclusions: Significant antitumor activity was observed in all the arms. Weekly nab-P with bevacizumab appeared to have the highest therapeutic index. However, sensory neuropathy was treatment limiting, which suggests that a 3 weeks on and 1 week off schedule should be explored. © 2013 Elsevier Inc. All rights reserved. |
| Keywords: | adult; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; fatigue; neutropenia; bevacizumab; cancer combination chemotherapy; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; bone metastasis; paclitaxel; cancer patient; neurotoxicity; metastasis; drug eruption; phase 2 clinical trial; sensory neuropathy; breast cancer; anemia; nausea; neuropathy; randomized controlled trial; thrombocytopenia; peripheral neuropathy; bone pain; antineoplastic activity; arthralgia; febrile neutropenia; nail disease; lung metastasis; dosage schedule comparison; nail; visceral metastasis; open study; combination therapy; recombinant granulocyte colony stimulating factor; breast metastasis; epistaxis; taxanes; chemotherapy induced anemia; nanoparticle albumin-bound paclitaxel; human epidermal growth factor receptor 2 negative |
| Journal Title: | Clinical Breast Cancer |
| Volume: | 13 |
| Issue: | 4 |
| ISSN: | 1526-8209 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2013-08-01 |
| Start Page: | 239 |
| End Page: | 246 |
| Language: | English |
| DOI: | 10.10167i.clbc.2013.02.008 |
| PROVIDER: | scopus |
| PUBMED: | 23829890 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 November 2013" - "CODEN: CBCLB" - "Source: Scopus" |
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