Phase II trial of metronomic capecitabine and cyclophosphamide with lapatinib and trastuzumab in patients with HER2-positive metastatic breast cancer.

Abstract

e12508 Background: Metronomic chemotherapy is an emerging paradigm of cancer therapy in which low doses of chemotherapy are delivered at frequent intervals. Activity in patients with metastatic breast cancer (MBC) has been demonstrated in several phase II clinical trials. Methods: We proposed a regimen with metronomic chemotherapy and dual HER2 inhibition in HER2 positive patients with MBC. We hypothesized that this regimen will be highly active in MBC and have a favorable toxicity profile. Patients were treated on a 21-day cycle with capecitabine 1500mg PO daily, cyclophosphamide 50mg daily, lapatinib 1000mg PO daily and trastuzumab 6mg/kg IV once per 21-day cycle. This regimen was continued until disease progression or unacceptable toxicity. Primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety and tolerability of this regimen. Eligibility criteria were patients 18 years of age and older who had histologically confirmed HER2-positive metastatic breast cancer with prior trastuzumab use in the adjuvant or metastatic setting with no more than two prior regimens for MBC. Results: Ten patients were accrued from Jan 2014-Oct 2016. Median age was 52 (range 38 - 79) years. Median number of chemotherapy regimens for metastatic disease was 0.5 (range 0-2). Median PFS was 13.7 (95% CI: 2.6, 16.6) months. Median OS was 29.6 (95% CI: 11.8, 60.5+) months. ORR was 30%, and CBR was 70%. Grade 3 or 4 toxicities were identified in 6 patients. The most common toxicities of any grade were fatigue (100%), diarrhea (80%), anemia, neutropenia, ALT increase, nausea and hand-foot syndrome 50% each. One patient achieved CR for over 3 years and continues on treatment at time of this report. 8 patients progressed and 1 patient withdrew from study without response evaluation. The trial was closed due to lack of accrual. Conclusions: The proposed regimen of metronomic capecitabine and cyclophosphamide with lapatinib and trastuzumab appears to be active in patients with HER2 positive MBC but with significant toxicity. Clinical trial information: NCT01873833.