| General information |
| Database: | DB01083 |
| Objective: | This multicenterphase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed human epidermal growth factor receptor 2+ inflammatory breast cancer. |
| Authors: | Cristofanilli M, et al |
| Title: | A randomizedphase II study of lapatinib + pazopanib versus lapatinib in patients with human epidermal growth factor receptor 2+ inflammatory breast cancer. |
| Journal: | Breast Cancer Res Treat. |
| Year: | 2013 |
| PMID: | 23239151 |
| Trial Design |
| Clinical Trial Id: | NCT00243503 |
| Agent: | lapatinib, pazopanib
|
| Target: | NA
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | human epidermal growth factor receptor 2+ inflammatory breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | lapatinib + pazopanib |
| Study Type: | A randomizedphase II study |
| Key Patients Feature: | Women aged more than and equal to 18 years with histologically or cytologically confirmed relapsed or refractory human epidermal growth factor receptor 2 overexpressing or amplified IBC were enrolled in two cohorts. Eligible patients had received prior chemotherapy including prior trastuzumab where available. |
| Biomarker: | human epidermal growth factor receptor 2 |
| Biomark Analysis: | NA |
| Control Group Info: | lapatinib alone |
| Treatment Info: | In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1, 500 mg + placebo or lapatinib 1, 500 mg + pazopanib 800 mg (doubleblind) once daily until disease progression, unacceptable toxicity, or death. Due to highgrade diarrhea observed with this dose combination in another study (VEG20007), Cohort 1 was closed. The protocol was amended such that an additional 88 patients (Cohort 2) were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1, 500 mg, lapatinib 1, 000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, respectively. |
| Primary End Point: | overall response rate (ORR). |
| Secondary End Point: | duration of response, progression free survival (PFS), overall survival, and safety. |
| Patients Number: | 76 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | In Cohort 1, ORR for the lapatinib (n = 38) and combination (n = 38) arms was 29 and 45 %, respectively; In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In Cohort 1, median PFS was 16.1 and 14.3 weeks;In cohort 2, median PFS was 16.0, 16.0, and 11.4 weeks, respectively. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | In cohort 1, Grade more than and equal to 3 adverse events (AEs) were more frequent in the combination arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 %, respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). In cohort 2, In the lapatinib, combination, and pazopanib therapy arms, grade more than and equal to 3 AEs were reported for 17, 50, and 46 % of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 %, respectively. |
| Conclusions: | The lapatinibpazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with singleagent lapatinib was confirmed in this population. |