Ibrance (palbociclib)

P3, N=603, Active, not recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 --> Jan 2026

Real-world data reveal drug- and age-specific toxicity differences. Ribociclib and abemaciclib pose higher risks in older adults compared to palbociclib, supporting the need for personalized treatment and careful monitoring in older patients.

Patients with metastatic HR+HER2- IBC demonstrated a shorter time on treatment suggesting shorter duration of response on CDKI + HT, which is markedly inferior to reported data for non-IBC patients from phase III trials.

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P=N/A, N=42, Completed, Pfizer | N=28 --> 42

At a WTP threshold of $150,000 per evLY, ribociclib demonstrated an approximately 100% probability of being cost-effective relative to palbociclib. Ribociclib improved health outcomes with a minimal relative cost increase and is therefore a highly cost-effective 1 L treatment option vs. palbociclib in patients with HR+/HER2- aBC from the Medicare perspective.

To overcome these limitations, we propose a senescence-primed ferroptosis strategy using a metal-organic framework (MOF)-based nanoplatform (ZPG) that codelivers CDK4/6 inhibitor (palbociclib) and ferroptosis inducer (gallium ions, Ga3+) to enhance antitumor efficacy...Leveraging ZPG for the codelivery of therapeutic agents, the synergistic mechanism resulted in markedly enhanced antitumor efficacy both in vitro and in vivo, with minimal off-target toxicity. Collectively, the ZPG-enabled senescence-primed ferroptosis strategy provides a promising and mechanistically rational approach for improving cancer therapy.

We assessed ctDNA with the RaDaR assay in NeoRHEA (NCT03065621), a single-arm, phase II neoadjuvant palbociclib plus endocrine therapy trial over 4 months (4 × 28-day cycles)...Baseline ctDNA predicted poor response to this regimen, supporting ctDNA as a biomarker to guide treatment in HR + /HER2-negative disease. Trial registration: EU Clinical Trials Register (EudraCT 2016-000879-24; registered 15 February 2017).

P1/2, N=45, Recruiting, West China Hospital | Not yet recruiting --> Recruiting | Trial completion date: Apr 2028 --> Sep 2028 | Initiation date: Apr 2025 --> Sep 2025 | Trial primary completion date: Apr 2027 --> Sep 2027

In the two cases we reported, first-line palbociclib therapy shows adequate and timely responses for premenopausal HR+/HER2- metastatic breast cancer patients. Although not widely utilized, frontline therapy with palbociclib combined with endocrine treatments may be a choice for HR+/HER2- metastatic breast cancer patients experiencing severe visceral metastasis.

Combining palbociclib, trastuzumab, and ET was safe and improved significantly PFS, compared to TPC in previously treated HER2-positive, PAM50 luminal A/B ABC patients.

CDK4/6 inhibitors have distinct toxicity profiles. Effective AE management and dose adjustments are crucial for maintaining efficacy, emphasizing the need for AE prediction models to optimize CDK4/6i use in HR + HER2 - aBC.