Entry Detail
| General information | |
| Database: | DB01064 |
| Objective: | Lapatinib Plus NabPaclitaxel As First And Second Line Therapy In human epidermal growth factor receptor 2+ MBC |
| Authors: | Denise A. Yardley |
| Title: | Phase II study evaluating lapatinib in combination with nabpaclitaxel in human epidermal growth factor receptor 2overexpressing metastatic breast cancer patients who have received no more than one prior chemotherapeutic regimen. |
| Journal: | Breast Cancer Res Treat |
| Year: | 2013 |
| PMID: | 23224144 |
| Trial Design | |
| Clinical Trial Id: | NCT00709761 |
| 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: | lapatinib + nabpaclitaxel |
| Study Type: | an openlabel, singlearm, multicenter, phase II study (NCT0070976I) to evaluate the efficacy and safety of nabpaclitaxel plus lapatinib in women with human epidermal growth factor receptor IIpositive MBC who had received no more than one prior chemotherapeutic regimen in the metastatic setting. |
| Key Patients Feature: | Female patients C18 years of age with histologically confirmed human epidermal growth factor receptor 2positive invasive breast cancer (defined as human epidermal growth factor receptor 2 positive score [[2.2] by fluorescence in situ hybridization or 3 amplification by immunohistochemistry) who presented with de novo stage IV disease or had stage IV disease at a relapse after curativeintent surgery were enrolled in the study. patients were required to have received no more than one prior chemotherapeutic regimen in the metastatic setting. |
| Biomarker: | human epidermal growth factor receptor 2overexpressing |
| Biomark Analysis: | Lapatinib 1, 000 mg with nabpaclitaxel 100 mg/m(2) IV is feasible with manageable and predictable toxicity and an ORR of 53 % comparing favorably with other human epidermal growth factor receptor 2based combinations in this setting. |
| Control Group Info: | single arm |
| Treatment Info: | initial doses ofnabpaclitaxel (125 mg/m2 IVonDay 1, 8, and 15 every 28 days) in combination with lapatinib (1, 250 mg orally once daily on a continuous basis) in a 4week cycle for a planned minimum of six cycles was performed. however, during the ongoing safety review of the first five patients, Grade 3 toxicities were observed in all five patients (four with neutropenia and one with neutropenic fever and diarrhea) and the decision was made to reduce the dose of both study drugs. All subsequent patients (n = 55) received nabpaclitaxel (100 mg/m2 IV on Day 1, 8, and 15 every 28 days) in combination with lapatinib (1, 000 mg orally once daily on a continuous basis) in a 4week cycle for a minimum of six cycles. |
| Primary End Point: | the overall response rate (ORR). |
| Secondary End Point: | progression free survival (PFS), overall survival, duration of response (DoR), time to response (TTR), and time to progression (TTP). |
| Patients Number: | 60 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Investigatorassessed ORR was 53 % (n = 32, 95 % confidence interval (CI): 40.7-66.0). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 39.7 weeks (95 % CI 34.1-63.9) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most commonly reported AEs were diarrhea, fatigue, nausea, and rash. The maximum toxicity grade of the majority of frequently reported AEs was Grade 1 or 2. Grade 3 diarrhea was reported at a frequency of 20 %, contributing to a high overall frequency (62 %) of AEs with a maximum toxicity Grade of 3. AEs of neutropenia also reached a maximum toxicity Grade of 3 for 22 % of patients. A total of five patients (8 %) experienced Grade 4 events (diarrhea, nausea, fatigue, febrile neutropenia, and hypokalemia) and all these AEs were considered treatmentrelated. |
| Conclusions: | The data in this study are consistent with those reported for other studies of lapatinib in combination with paclitaxel. Although this study was not designed for inference testing, the results suggest a promising signal of efficacy and no new safety signals. |