Drug combination shows promise in metastatic breast cancer
Drug combination shows promise in metastatic breast cancer
14 Jul 2015The combination of lapatinib (Tykerb) and trastuzumab (Herceptin) is active and well-tolerated when given to breast cancer patients, a new non-randomized phase 2 study shows. The results relate to patients with human epidermal growth factor receptor 2-positive (HER2) metastatic breast cancer (MBC) who have received up to two lines of therapy for advanced disease.
What's more, early metabolic imaging by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) appears to provide the key to selecting patients who can be treated with targeted regimens and spared the toxicity of chemotherapy, Nancy U. Lin, MD, Susan F. Smith Center for Women's Cancers, Dana-Farber Cancer Institute, Boston, Ma., and colleagues reported.
“Most of the patients achieved clinical benefit”
In the study, two cohorts of patients with MBC at the Susan F. Smith Center for Women's Cancers were enrolled between May 2007 and October 2010. Of the 87 patients registered, 85 were evaluable for efficacy.
Patients in cohort one had no prior trastuzumab for MBC and had at least one year from adjuvant trastuzumab. Patients in cohort two had received 1-2 lines of chemotherapy including trastuzumab for MBC and/or recurrence of less than one year from adjuvant trastuzumab.
Initially, patients received lapatinib 1,000 mg orally once per day and intravenous trastuzumab at 2 mg/kg (following a 4-mg/kg loading dose) once per week. In July 2009, the study was amended to allow trastuzumab 6 mg/kg (after an 8-mg/kg loading dose) once every three weeks.
In all, according to study author, the analysis of the results showed that:
- 57% of patients in cohort one and 40.0% of patients in cohort two achieved clinical benefit
- The confirmed objective response rate was 50.0% in cohort one and 22.2% in cohort two
- In addition, the study demonstrated that lack of metabolic response by 18F-FDG-PET/CT at week one was highly predictive of poor response for cohort one and 91% for cohort two.
Reported reasons for discontinuation
The median follow-up for all surviving patients was 37.1 months (maximum 72.8 months). The reasons for discontinuation of protocol therapy were:
- Progression in non-CNS only
- Isolated CNS progression
- Progression in both non-CNS and CNS
- Treatment-related toxicity
- Physician or patient decision or
- Review of baseline biopsy indicating the patient did not have MBC
10% of the patients in cohort one remained on protocol therapy for more than three years after study entry, said Lin. Among the 85 patients evaluable for efficacy, there were 49 deaths.
No treatment recommendations yet
"Use of early metabolic imaging as a clinically relevant biomarker merits additional investigation, particularly in studies with molecularly targeted therapies," said Lin. She noted that molecular correlative analyses of metastatic specimens are now underway to elucidate mechanisms of HER2 resistance.
Lin acknowledged that the 18F-FDG-PET/CT analyses are exploratory and will need to be confirmed before early metabolic response can influence treatment recommendations.
Source: MedPage Today