Pertuzumab Plus Trastuzumab in Patients With Endometrial Cancer With <i>ERBB2/3</i> Amplification, Overexpression, or Mutation: Results From the TAPUR Study.

Abstract

The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with <i>ERBB2</i> or <i>ERBB3 (ERBB2/3)</i> amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported. Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with <i>ERBB2/3</i> amplification, overexpression, or mutation. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+) duration. Secondary end points include safety, duration of response, duration of SD, progression-free survival (PFS), and overall survival (OS). Twenty-eight patients were enrolled from March 2017 to November 2019; all patients were evaluable for efficacy and toxicity. Seventeen patients had tumors with <i>ERBB2/3</i> amplification and/or overexpression, eight with both <i>ERBB2</i> amplification and <i>ERBB2/3</i> mutations, and three with only <i>ERBB2</i> mutations. Ten patients had DC (two partial response and eight SD16+); all 10 had <i>ERBB2</i> amplification, and 6 of the 10 patients with DC had >1 <i>ERBB2/3</i> alteration. DC and OR rates were 37% (95% CI, 21 to 50) and 7% (95% CI, 1 to 24), respectively; the median PFS and median OS were 16 weeks (95% CI, 10-28) and 61 weeks (95% CI, 24-105), respectively. One patient experienced a grade 3 serious adverse event (muscle weakness) at least possibly related to P + T. P + T has antitumor activity in heavily pretreated patients with EC with <i>ERBB2</i> amplification and warrants additional study.