Goldstein LJ, et al. – This Phase I/II study was carried out to appraise the toxicity and response rate after treatment with suberoylanilide hydroxamic acid (SAHA) and trastuzumab in patients with HER2–overexpressing metastatic breast cancer with trastuzumab–resistant progressive disease. No dose-limiting toxicity (DLT) with SAHA 200 mg twice daily combined with trastuzumab were noticed in these patients. However, results shed light on insufficient statistical evidence that adding SAHA reversed trastuzumab resistance in these patients.

Methods

• In order to detect the dose level at which 0 or 1 patients experienced a dose-limiting toxicity (DLT) during the first cycle of therapy, the SAHA dose was modified in cohorts of 3–6 patients, in Phase I.
• Furthermore, response to the recommended dose identified in Phase I was based on the response evaluation criteria in solid tumors, in the Phase II study.
• Additionally, experts assessed overall survival and time to progression.

Results

• As per the observations, the recommended dose was determined to be 200 mg twice a day on days 1–14 and IV trastuzumab 6 mg/kg on day 1 of a 21-day cycle (n = 6).
• When the pre-planned efficacy evaluation found that none of the patients in the primary analysis set responded to combination SAHA and trastuzumab treatment, the Phase II study (n = 10) was terminated.