PET/CT Predicts Response to Drug Combo in HER2-Positive Breast Cancer

The combination of lapatinib plus trastuzumab for patients with metastatic HER2-positive breast cancer resulted in high response rates when used early. Additionally, undergoing [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) 1 week into therapy could predict response to this treatment.

These results from the phase II Translational Breast Cancer Research Consortium (TBCRC) 003 trial were published in the Journal of Clinical Oncology.

The objective response rate among first-line patients was 50.0%, and 22.2% among second- and third-line patients combined. The clinical benefit rate for first-line patients was 57.5%, and 40.0% for second- and third-line patients.

The non-randomized trial recruited 41 first-line patients who had not previously received trastuzumab for their metastatic breast cancer. A separate cohort of 45 second- and third-line patients did receive prior lines of trastuzumab in the metastatic setting.

Median progression-free survival was 7.4 months in the first-line group and 5.3 months in the second- and third-line group. The 3-year survival rates were 61.7% and 38.6% in the first-line group and second- and third-line group, respectively.

An [18F]FDG-PET/CT scan at 1 week was able to discern whether a patient would respond to treatment. [18F]FDG-PET/CT, in contrast to CT imaging alone, is able to detect tumor metabolism. A lack of an [18F]FDG-PET/CT response at 1 week was associated with a failure to achieve an objective response as measured by Response Evaluation Criteria in Solid Tumors (RECIST). The negative predictive value was 91% for both the previously treated and untreated cohorts.

“While these results are not practice-changing given their exploratory nature, we believe that they strongly support further investigation of this and other molecular imaging techniques in the context of prospective trials,” said study author Nancy U. Lin, MD, of Dana-Farber Cancer Institute in Boston. “Our hope is that such techniques may allow for more personalized tailoring of treatment regimens in the future.”

Frequent adverse events included diarrhea, fatigue, and rash. Grade 3 diarrhea occurred in less than 10% of patients. Four patients (5%) had a decrease in left ventricular ejection fraction (LVEF) to below 50%, but all four recovered their LVEF and continued on therapy. There were no high-grade cardiac events reported on the trial. Dose reductions or holding back of dosing were needed in less than 10% of patients, mostly for rash and diarrhea.

Since the registration of this trial, between 2007 and 2010, the US Food and Drug Administration (FDA) has approved novel therapies for metastatic HER2-positive breast cancer, including pertuzumab and trastuzumab emtansine (T-DM1). First-line standard of care for metastatic HER2-positive disease is trastuzumab plus pertuzumab and a taxane, while second-line therapy is typically T-DM1. Lapatinib plus trastuzumab is currently included in the American Society of Clinical Oncology (ASCO) clinical practice guidelines as a third-line or later therapy, Lin told Cancer Network.

“Whole-exome sequencing was also performed on some tumor specimens and these are now being analyzed and linked to patients’ outcomes,” said Lin. “Because of the unique study design including required biopsy at study entry and targeted-only treatment without chemotherapy, we believe this trial affords a unique opportunity to hone in on mechanisms of resistance to HER2-directed therapy.”