Temsirolimus (T) in patients (pts) with colorectal cancer (CRC) with PIK3CA mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

Abstract

106 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with PIK3CA mutation treated with T are reported. Methods: Eligible pts had advanced CRC with PIK3CA mutation reported by a genomic test performed in a CLIA-certified, CAP-accredited site selected lab, no standard treatment options, measurable disease, ECOG performance status (PS) 0-2, and adequate organ function. Use of T was approved by the TAPUR Molecular Tumor Board in each case. After antihistamine pre-treatment, T was administered at 25 mg IV over 30-60 minutes weekly until disease progression. Primary endpoint was disease control (DC), defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease at 16+ weeks (SD 16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 has DC, 18 more pts are enrolled; otherwise, the study stops for futility. If ≥7 of 28 pts has DC, the null DC rate is rejected. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 10 pts (60% male) with CRC with PIK3CA mutation were enrolled from November 2017 to May 2020. All were eligible for efficacy and toxicity. Demographics and outcomes are summarized in Table. No objective responses (OR) were observed. 1 pt had SD of 16.1 wks duration for a DC rate of 10% (95% CI: 0%, 45%); the null DC rate of 15% was not rejected (p=0.80). 6 pts had at least one grade 3-4 adverse or serious adverse event (AE/SAE) at least possibly related to T, including acute kidney injury, dehydration, decreased platelet count hypertriglyceridemia, mucositis, neutropenia, and scrotal and penile edema. Conclusions: Monotherapy T does not have sufficient clinical activity in CRC pts with PIK3CA mutation for continued evaluation in this pt population. Other treatments should be considered for these pts, including treatments offered in clinical trials. Clinical trial information: NCT02693535. [Table: see text]