An open label, phase II, multicenter, study to evaluate the efficacy and safety of pertuzumab (P) in chemotherapy naïve patients (pts) with hormone refractory prostate cancer (HRPC)

Abstract

4609 Background: P is the 1st of a new class of targeted therapeutics known as HER-dimerization inhibitors (HDI). P is a human monoclonal antibody that blocks ligand-associated heterodimerization of HER2 with other HER kinase family members, thereby inhibiting intracellular signaling. Preclinical activity of P in prostate cancer xenografts has been demonstrated. Methods: P was administered IV once every 3 weeks at 420 mg (with a loading dose of 840 mg) or 1050 mg (without a loading dose) in consecutive cohorts. An interim analysis was performed for each cohort after inclusion of 23 evaluable pts. In case of > 3 responses, 27 additional pts were to be enrolled in that cohort. The 1050 mg cohort was only to be opened, if the 420 mg cohort showed ≤ 3 responses. Eligibility criteria were: progressing chemotherapy naïve HRPC, LVEF ≥ 50%. The primary endpoint in this study was PSA (prostate specific antigen) response rate (RR) at 24 weeks after start of single agent P. Secondary endpoints were safety profile, overall RR by RECIST, time to tumor progression (TTP), and overall survival (OS). Results: 23 evaluable pts in each cohort were included in the interim analysis. No PSA responses were observed with a median TTP (PSA) of 5 weeks. One unconfirmed 75% decrease in PSA was found after the interim analysis. P was well tolerated. Most common adverse event in the 46 pts was grade 1 & 2 diarrhea (48%). Nausea was reported for the 420 mg- and 1050 mg dose level respectively in 22 & 9% and asthenia in 35 & 13%. No LVEF decreases of ≥ 15% and to below 50% were observed in either cohort. No congestive heart failure was reported. Conclusions: P is safe and well tolerated. No difference in toxicity was observed between the two dose levels. There is insufficient evidence of activity in this prostate cancer study. A combination (either chemo or hormonal) or pt selection strategy may be investigated in the future. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche AstraZeneca, Boehringer Ingleheim, Celgene, Novartis