Entry Detail
| General information | |
| Database: | DB01054 |
| Objective: | Paclitaxel in Combination with Lapatinib in human epidermal growth factor receptor 2Overexpressing Metastatic Breast Cancer |
| Authors: | Agnieszka JagielloGruszfeld |
| Title: | A singlearmphase II trial of firstline paclitaxel in combination with lapatinib in human epidermal growth factor receptor 2overexpressing metastatic breast cancer. |
| Journal: | Oncology |
| Year: | 2010 |
| PMID: | 21088439 |
| Trial Design | |
| Clinical Trial Id: | NCT00356811 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | paclitaxel + lapatinib |
| Study Type: | a phase II, openlabel, singlearm, multicenter study of lapatinib and paclitaxel as firstline therapy for MBC. |
| Key Patients Feature: | Patients with histologically confirmed, invasive, stage IV breast cancer who were fluorescence in situ hybridization (FISH)positive for human epidermal growth factor receptor 2 in primary or metastatic tissue and had previously untreated metastatic disease were eligible. Patients with estrogen receptor (ER)positive and/or progesterone receptor (PgR)positive, or unknown disease were eligible only if they had symptomatic visceral disease requiring chemotherapy, a rapidly progressing or lifethreatening disease, or were no longer benefiting from endocrine therapy. Prior adjuvant or neoadjuvant chemotherapy as well as hormonal therapy were permitted. A diseasefree interval of more than and equal to 12 months since the completion of a prior taxane regimen was required. Prior EGFR or human epidermal growth factor receptor 2targeted therapy in any setting was not permitted. Bisphosphonates were allowed if initiated prior to the first study dose. |
| Biomarker: | human epidermal growth factor receptor 2overexpressing |
| Biomark Analysis: | Firstline lapatinib plus paclitaxel for human epidermal growth factor receptor 2overexpressing MBC produced an encouraging ORR with manageable toxicities |
| Control Group Info: | NA |
| Treatment Info: | paclitaxel (80 mg/m 2 i.v. weekly for 3 weeks every 4 weeks) for 6 6 cycles plus daily lapatinib (1, 500 mg/day) until disease progression or until withdrawal due to toxicity or withdrawal of consent. Single dose reductions were permitted for both lapatinib and paclitaxel. Dose delays of up to 2 weeks for lapatinib were permitted for hematologic and nonhematologic toxicities, with the exception of cardiac toxicity where a 3week dose delay was allowed. Paclitaxel dose delays were also permitted for hematologic and nonhematologic toxicities. |
| Primary End Point: | the overall response rate (ORR). |
| Secondary End Point: | the duration of response (DoR), time to response, time to progression, progression free survival (PFS), overall survival, and the incidence and severity of adverse events. |
| Patients Number: | 57 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The IRCassessed ORR was 51% (29/57 patients with complete or partial response) while the investigatorassessed ORR was 77% (44/57). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS was 47.9 weeks (95% CI: 40.0 to NA) according to the IRC and 50.9 weeks (95% CI: 47.0- 64.3) as assessed by the investigator. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common toxicities were diarrhea (56%), neutropenia (44%), rash (40%), fatigue (25%), and peripheral sensory neuropathy (25%). |
| Conclusions: | Firstline lapatinib plus paclitaxel for human epidermal growth factor receptor 2overexpressing MBC produced an encouraging ORR with manageable toxicities. This combination may be useful in firstline treatment for patients with human epidermal growth factor receptor 2overexpressing MBC and supports the ongoing evaluation of this combination as firstline therapy in human epidermal growth factor receptor 2overexpressing MBC. |