| General information |
| Database: | DB01025 |
| Objective: | Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant onceperweek paclitaxel followed by dosedense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triplenegative breast cancer |
| Authors: | William M. Sikov |
| Title: | Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant onceperweek paclitaxel followed by dosedense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triplenegative breast cancer: CALGB 40603 (Alliance). |
| Journal: | journal of clinical oncology |
| Year: | 2015 |
| PMID: | 25092775 |
| Trial Design |
| Clinical Trial Id: | NCT00861705 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | addition of carboplatin and/or bevacizumab to neoadjuvant onceperweek paclitaxel followed by dosedense doxorubicin and cyclophosphamide |
| Study Type: | a randomized, openlabelphase II study. After stratification by baseline clinical stage (II v III), patients had an equal probability of assignment to any of the four treatment arms. |
| Key Patients Feature: | Eligible patients had operable, biopsyconfirmed, previously untreated, clinical stage II to III noninflammatoryinvasive breast cancer, with ER and PgR expression less than and equal to 10% and human epidermal growth factor receptor 2 negativity, defined by immunohistochemical (IHC) staining 0 to 1+ or fluorescence in situ hybridization ratio<2.0 if IHC 2+or IHC not performed. Adequate hematologic, renal, and hepatic function, normal cardiac function by echocardiogram or radionuclide ventriculogram, and a negative pregnancy test in women of childbearing potential were required. patients were excluded for grademore than and equal to 2 neuropathy or contraindications to treatment with bevacizumab, including uncontrolled hypertension. |
| Biomarker: | triplenegative |
| Biomark Analysis: | NA |
| Control Group Info: | Arm 1: wPddAC; Arm 2: wPddAC + Bev; Arm 3: wPCarboddAC; Arm 4: wPCarboddAC + Bev |
| Treatment Info: | Patients (N=443) with stage II to III TNBC received paclitaxel 80mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. |
| Primary End Point: | The overall study was designed to detect increases in the pCR breast rate from 35% in the control group to 55% for either carboplatin or bevacizumab (onesided ¦Á of 0.05). |
| Secondary End Point: | pCR breast/axilla, treatment delivery, treatmentrelated toxicities (as defined byCommon Toxicity Criteria for Adverse Events, version 4.0), RCB, conversion from clinically nodepositive to pathologically nodenegative status, and conversion from BCSineligible to BCSeligible status after treatment. Patients will be monitored for RFS, time to first failure, and OS for 10 years. |
| Patients Number: | 454 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Adding either agent significantlyincreased thepCRbreast rate;60%of patients who received carboplatin achieved pCR breast compared with 46% of those who did not (odds ratio [OR], 1.76; P = .0018). Patients treated with a bevacizumabcontaining regimen had a pCR breast rate of 59% compared with 48% of those who were not (OR, 1.58; P= .0089). Patients assigned to both agents (arm four) had the highestpCRbreast rate (67%), withnosignificant interactionbetween their effects (P= .52). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Incidence of grade 3 to 4 neutropenia and thrombocytopenia was higher with the addition of carboplatin; however, incidence offebrile neutropenia, was significantly higher only in arm four. Patients assigned to bevacizumab were more likely to develop grade3hypertension(10%to12%v0%to2%), andtheonlyonstudy death was attributed to uncontrolled hypertension. |
| Conclusions: | In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapsefree or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent. |