Entry Detail
| General information | |
| Database: | DB01058 |
| Objective: | Lapatinib plus Letrozole as FirstLine Therapy for HER2+ Hormone Receptor-Positive Metastatic Breast Cancer |
| Authors: | LEE S. SCHWARTZBERG |
| Title: | Lapatinib plus letrozole as firstline therapy for HER2+ hormone receptorpositive metastatic breast cancer. |
| Journal: | The Oncologist |
| Year: | 2010 |
| PMID: | 20156908 |
| Trial Design | |
| Clinical Trial Id: | NCT00073528 |
| 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 plus letrozole |
| Study Type: | a randomized, doubleblind, controlled, parallelgroup, multicenter, phase III study with stratification by interval since completion of prior adjuvant antiestrogen therapy (at least 6 months or no prior therapy versus <6 months) and location of metastatic sites (soft tissue or visceral versus boneonly disease). |
| Key Patients Feature: | Postmenopausal women with ER+ or progesterone receptor-positive (i.e., HR+), histologically confirmed, advanced breast cancer or MBC(stage IIIb/c or stage IV) were enrolled |
| Biomarker: | HER2+ hormone receptorpositive |
| Biomark Analysis: | The addition of lapatinib to letrozole is well tolerated and leads to a significantly greater PFS time, ORR, and CBR than with letrozole alone in women with MBC who coexpress HR and HER2. |
| Control Group Info: | letrozole plus placebo |
| Treatment Info: | oral treatment with letrozole (2.5 mg) plus lapatinib (1, 500 mg) versus letrozole (2.5 mg) plus placebo |
| Primary End Point: | progression free survival (PFS) in HER2+ patients |
| Secondary End Point: | NA |
| Patients Number: | 219 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The ORR was also significantly higher in lapatinibtreated patients (28%, versus 15%; odds ratio [OR], 0.4; 95% CI, 0.2-0.9; p = .021) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS times in HR+ HER2+ patients were 3.0 months in the letrozole plus placebo group and 8.2 months in the letrozole plus lapatinib group. The HR for the risk for progression was 0.71 favoring the lapatinib group (95% confidence interval [CI], 0.53-0.96; p = .019) |
| Median OS A vs. C: | the median OS times were 32.3 months in the letrozole plus placebo group and 33.3 months in the letrozole plus lapatinib group. |
| Adverse Event(agent arm): | Adverse events were reported in 77% of patients in the letrozole plus placebo group and in 96% of patients in the letrozole plus lapatinib group. In both groups, adverse events were primarily grade 1 and 2. The most common adverse events in the letrozole plus lapatinib group were diarrhea (68%), rash (46%), nausea (27%), fatigue (22%), and arthralgia (18%), and in each case, with the exception of arthralgia, the incidence was greater than in the letrozole plus placebo group. |
| Conclusions: | The addition of lapatinib to letrozole is well tolerated and leads to a significantly greater PFS time, ORR, and CBR than with letrozole alone in women with MBC who coexpress HR and HER2. |