Phase 1 trial of exercise as first-line therapy for hormone receptor (HR)–positive advanced breast cancer (TBCRC 054).

Abstract

1088 Background: Observational studies show post-diagnosis exercise is associated with reduced risk of cancer death in patients with HR-positive breast cancer. We conducted a phase 1a dose-finding trial of exercise therapy as first-line treatment for HR-positive advanced breast cancer (TBCRC 054). Methods: This multicenter trial was conducted using a patient-centric, decentralized platform (NCT03988595). Non-exercising patients receiving first line endocrine plus CDK4/6 inhibitor therapy were allocated using an adaptive continual reassessment design to one of four escalated exercise therapy dose levels (range: 90 to 300 min/week) of individualized, moderate-intensity treadmill walking for 6 consecutive months. The trial was later amended to add a fifth dose level of 375 min/week and to allow dose cohort backfilling. Exercise therapy sessions were conducted remotely in patient’s homes with real-time monitoring. The primary objective was to identify the recommended phase 2 dose (RP2D) as determined by feasibility and preliminary clinical efficacy. Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if ≥70% of patients achieved a REDI ≥75%. One-year progression free survival (PFS) rates were assessed by the Kaplan-Meier method. Results: Fifty-four women (median age 53 [46 to 63] years) were enrolled between August 2019 and April 2024; 23 (43%) had visceral metastases, 43 (80%) received an aromatase inhibitor, 11 (20%) received fulvestrant, and 53 (98%) received a CDK4/6 inhibitor. The proportion of patients with REDI ≥75% in each dose level was: 90 min/week (n = 10): 80%, 150 min/week (n = 10): 60%, 225 min/week (n = 11): 82%, 300 min/week (n = 13): 62%, and 375 min/week (n = 10): 40%. Among the two feasible dose levels (90, 225 min/week), 1-year PFS rate was 70% (95% CI, 47% to 100%) in the 90 min/week dose level and 91% (95% CI 75% to 100%) in the 225 min/week dose level. No serious adverse events were observed. Overall, 225 min/week (~ 45 minutes per treatment at 5 times weekly) was selected as the RP2D. Conclusions: This multicenter phase 1 trial showed that exercise therapy doses of 90 and 225 min/week are feasible and safe in patients receiving first line endocrine-based therapy. These data also support the rationale for a phase 2 trial testing the preliminary clinical efficacy of exercise at the RP2D of 225 min/week in HR-positive advanced breast cancer. Clinical trial information: NCT03988595 .