Clinical Design and Primary Endpoint

The University of Miami-led FastER trial is a randomized behavioral intervention trial enrolling 260 participants across three U.S. sites, starting in September 2024 and with a primary completion expected in September 2028. As a non-pharmacologic behavioral intervention, it is not formally classified under a specific Phase and is currently recruiting. The 12-week intervention includes 12–14 hours of overnight fasting, three weekly sessions of moderate-to-vigorous aerobic and resistance exercise, a combination of both interventions, and a control group receiving health education. The primary endpoint is the change in fatigue measured by EORTC QLQ-C30, with PRO-CTCAE toxicity, psychological distress, physical function, and CT-based body composition tracked for 12 months to assess sustainability.

Target Population and Drug Regimen

The trial targets postmenopausal HR-positive, locally advanced or metastatic breast cancer patients who have started first- or second-line endocrine therapy and CDK4/6 inhibitors within 90 days. Permitted drugs include Pfizer’s Ibrance and palbociclib, Novartis’s Kisqali and ribociclib, and Eli Lilly’s Verzenio and abemaciclib, all of which inhibit CDK4 and CDK6. HER2-positive patients may also receive Roche’s Herceptin (trastuzumab) and Perjeta (pertuzumab) as HER2-targeted antibodies, and patients receiving PI3K inhibitors are included to reflect real-world treatment settings. The standard-of-care comparator is aromatase inhibitor- or fulvestrant-based endocrine therapy, with subsequent options including PIK3CA mutation-targeted PI3K/AKT pathway therapies and antibody-drug conjugates after disease progression.

Regulatory and Market Context

FDA granted accelerated approval for Ibrance on February 3, 2015, and full approval on March 31, 2017. Kisqali received approval on March 13, 2017, and Verzenio on September 28, 2017, for advanced HR-positive, HER2-negative breast cancer. As a non-drug trial, this behavioral intervention is not subject to FDA, EMA, or PMDA approvals or advisory committee votes, but rather aims to generate evidence for patient care. In 2025, Verzenio generated USD 5.723 billion in global sales, Kisqali USD 4.783 billion, and the combined CDK4/6 class reached USD 14.6 billion. Therefore, results that reduce fatigue and toxicity to prolong treatment duration could enhance real-world value and healthcare resource efficiency without altering the efficacy of existing drugs.

Clinical and Business Implications

Cancer-related fatigue can lead to dose reductions and treatment discontinuation, independently affecting long-term treatment outcomes and cost-effectiveness. FastER’s key innovation lies in testing a low-cost lifestyle intervention combined with remote coaching and Fitbit monitoring, offering a scalable operational model. However, fatigue is influenced by disease progression, anemia, sleep, and drug-specific toxicities, so the intervention effects must be clearly differentiated in randomized controlled trials and 12-month follow-ups. If positive, the results are more likely to influence supportive care guidelines, digital coaching services, and cancer survivorship programs than directly impact head-to-head competition among CDK4/6 inhibitors.