| General information |
| Database: | DB01071 |
| Objective: | Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive, Locally Advanced, or Metastatic Breast Cancer |
| Authors: | Kathy D. Miller |
| Title: | Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2positive, locally advanced, or metastatic breast cancer. |
| Journal: | journal of clinical oncology |
| Year: | 2014 |
| PMID: | 24733796 |
| Trial Design |
| Clinical Trial Id: | NCT00875979 |
| Agent: | Trastuzumab Emtansine
|
| Target: | human epidermal growth factor receptor 2 and microtubuleinhibitory
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | trastuzumab emtansine with pertuzumab |
| Study Type: | openlabel, singlearmphase Ib/IIa study |
| Key Patients Feature: | patients were at least 18 years old with histologically documented locally advanced breast cancer (defined as unresectable local or regional disease) or MBC with human epidermal growth factor receptor 2 gene amplification by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization and/or human epidermal growth factor receptor 2 protein overexpression by immunohistochemistry(IHC)3+. Patients in the advanced MBC expansion cohort must have disease that progressed following or while receiving human epidermal growth factor receptor 2directed therapy for known MBC. Patients in the firstline cohort were initially required to have received trastuzumab in the adjuvant or neoadjuvant setting; an amendment eliminated this requirement near the end of the enrollment period. Priortreatment withTDM1 or pertuzumab was not permitted. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, measurable disease, left ventricular ejection fraction (LVEF) of more than and equal to 55% by either echocardiogram (ECHO) or multiplegated acquisition scan (MUGA), and adequate hematologic and organ function. |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | Exploratory biomarker analyses demonstrated that patients with abovemedian tumor human epidermal growth factor receptor 2 mRNA levels had a numerically higher ORR than patients with belowmedian levels (44% v 33%, respectively). |
| Control Group Info: | single arm |
| Treatment Info: | 3.6 mg/kg TDM1 plus pertuzumab (840mg loading dose, then 420 mg subsequently) once every 3 weeks. |
| Primary End Point: | investigatorassessed objective response rate (ORR). |
| Secondary End Point: | NA |
| Patients Number: | 64 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The ORRwas41% overall, 33% in patients with advanced MBC, and 57% in firstline patients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survival was 6.6, 5.5, and 7.7 months, respectively. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade more than and equal to 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than40% after study drug discontinuation. |
| Conclusions: | TDM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the firstline and advanced MBC settings warrants further investigation. |