Entry Detail
| General information | |
| Database: | DB01046 |
| Objective: | Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Hormone ReceptorPositive Breast Cancer |
| Authors: | Harold J. Burstein |
| Title: | Endocrine therapy with or without inhibition of epidermal growth factor receptor and human epidermal growth factor receptor 2: a randomized, doubleblind, placebocontrolledphase III trial of fulvestrant with or without lapatinib for postmenopausal women with hormone receptorpositive advanced breast cancerCALGB 40302 (Alliance). |
| Journal: | journal of clinical oncology |
| Year: | 2014 |
| PMID: | 25348000 |
| Trial Design | |
| Clinical Trial Id: | NCT00390455 |
| 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: | 17 |
| Therapeutic Combination Content: | Endocrine therapy+laptinib |
| Study Type: | A Randomized, DoubleBlind, PlaceboControlledphase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer |
| Key Patients Feature: | Eligible women had estrogen receptor-positive and/or progesterone receptor-positive tumors, regardless of human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2) status, and prior aromatase inhibitor treatment. |
| Biomarker: | hormone receptorpositive |
| Biomark Analysis: | For human epidermal growth factor receptor 2positive tumors, lapatinib was associated with longer median PFS (5.9 v 3.3 months), but the differential treatment effect by human epidermal growth factor receptor 2 status was not significant (P = .53). |
| Control Group Info: | Fulvestrant plus placebo |
| Treatment Info: | fulvestrant 500 mg intramuscularly on day 1, followed by 250 mg on days 15 and 28 and every 4 weeks thereafter, and either lapatinib 1, 500 mg or placebo daily. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | toxicity, objective tumor response, and overall survival (OS). |
| Patients Number: | 295 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The incidence of objective response was 20% (95% CI, 13% to 29%) in the lapatinib arm compared with 9% (95% CI, 5% to 17%) in the placebo arm (P=.048) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 4.7 months for lapatinib plus fulvestrant and 3.8 months for placebo plus fulvestrant. TheHR(placebo to lapatinib) for PFS was 1.04 (95% CI, 0.82 to 1.33; onesided P= .37). |
| Median OS A vs. C: | The HR for OS was 0.91 (95% CI, 0.68 to 1.21; onesided P= .25). Median OS was 30 months for the lapatinib plus fulvestrant arm and 26.4 months for the placebo plus fulvestrant arm. |
| Adverse Event(agent arm): | No grade 4 or 5 adverse events were reported. More patients receiving lapatinib experienced grade 3 adverse events (19% v 5%; P < .001), most commonly acneiform rash, diarrhea, fatigue, and elevations in serum transaminases. Of 285 patients who completed protocol therapy, 20 (7%) ended treatment early because of toxicity, more frequently in the lapatinib arm (12% v 2%; P= .001), resulting in diarrhea, fatigue, and rash. No grade 3 or 4 cardiac toxicity was reported. |
| Conclusions: | Adding lapatinib to fulvestrant does not improve PFS or OS in advanced ERpositive breast cancer and is more toxic. |