Ibrance (palbociclib)

P3, N=315, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2027 --> Sep 2028

While generally well tolerated, their toxicity profiles differ, with palbociclib and ribociclib more commonly associated with hematologic toxicity and abemaciclib with gastrointestinal adverse effects such as diarrhea...We report a 65-year-old woman with metastatic HR+ breast cancer who presented with a two-week history of watery diarrhea (10-12 episodes/day), abdominal cramping, and a 5-pound weight loss while receiving palbociclib, fulvestrant, and denosumab...Although biopsy later demonstrated cytomegalovirus (CMV) positivity, antiviral therapy was deferred given negative CMV PCR and complete clinical resolution. This case highlights an uncommon presentation of palbociclib-induced pancolitis and underscores the importance of careful clinical evaluation and contextual interpretation of histologic findings to avoid unnecessary treatment.

Ribociclib and abemaciclib may provide superior rwPFS and OS compared to palbociclib in HR+/HER2- mBC patients with bone metastases..

P3, N=920, Recruiting, Eli Lilly and Company | N=274 --> 920

To achieve cost-effectiveness at WTP thresholds of $100,000, $150,000, and $200,000 per QALY, the per-cycle price of inavolisib would need to be reduced to 59.5%, 72.0%, and 86.5% of its current price, respectively.ConclusionFor patients with PIK3CA-mutated HR+/HER2- ABC, the inavolisib regimen is not cost-effective in the U.S. healthcare setting. Negotiating price reductions and adjusting decision thresholds based on patient characteristics may be viable strategies to meet the extensive treatment demand in the U.S.

Functional assays in BRCA cells were performed to evaluate the effects of MYO1B on cell proliferation, apoptosis, and sensitivity to tamoxifen and palbociclib. Mechanistically, MYO1B activated the Pi3k-AKT signaling pathway. Our study suggests that MYO1B promotes the progression of BRCA and may serve as a new target for overcoming endocrine therapy resistance.

Pexidartinib inhibited macrophage activity, suppressed STAT3 phosphorylation, reduced ARG1 expression, and increased lymphocyte viability, thereby enhancing the antitumor efficacy of palbociclib in HR + /HER2- breast cancer. These findings reveal a previously unrecognized immunosuppressive mechanism induced by CDK4/6 inhibition and support CSF1R blockade as a promising combination strategy.

P1/2, N=217, Completed, Arvinas Estrogen Receptor, Inc. | Active, not recruiting --> Completed

The CDK4/6 inhibitors abemaciclib and palbociclib have demonstrated promising results in patient-derived xenograft models of PM...While some cells showed sensitivity to Bcl-xL inhibitors, neither navitoclax nor the specific Bcl-xL inhibitor A-1331852, nor other BH3 mimetics targeting Bcl-2 (venetoclax) or Mcl-1 (S63845) increased cell death when combined with palbociclib...Therefore, we employed inhibitors of these pathways, such as dasatinib, momelotinib or Torin-1, which did not synergise with palbociclib to kill the cells...The differential effects of palbociclib and cisplatin on permanent growth arrest were verified by sorting PM cells based on size and β-galactosidase activity. Our findings underscore the importance of understanding the nature of therapy-induced senescence when assessing the effectiveness of senolytics in different tumour models.

P2, N=57, Active, not recruiting, Royal Marsden NHS Foundation Trust | Recruiting --> Active, not recruiting | N=324 --> 57 | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Sep 2026 --> Jun 2027

P2, N=157, Active, not recruiting, Pfizer | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026