Ibrance (palbociclib)

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (such as palbociclib, ribociclib, and abemaciclib) exert their effects by arresting the cell cycle at the G1/S checkpoint. From the perspective of laboratory medicine, we further emphasize the importance of biomarker detection, therapeutic target assessment, and precision molecular subtyping in identifying patients most likely to benefit from CDK4/6 inhibitor-based therapies. In addition, we discuss the role of these agents in remodeling the TIME, evaluate current combination strategies aimed at overcoming resistance, and highlight future directions for advancing this rapidly evolving field.

Together, these findings position palbociclib as a versatile therapeutic backbone in CRC. By simultaneously targeting cell cycle and oncogenic signaling networks, palbociclib-based combinations induce synergistic and durable responses, offering a compelling rationale for tailored therapeutic strategies in molecularly defined CRC.

 Switching CDK4/6i and ET conferred a statistically significant improvement of PFS in patients with progression or recurrence on prior CDK4/6i-containing therapy. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.

P1/2, N=1132, Recruiting, Hoffmann-La Roche | N=792 --> 1132

mRNA sequencing reveals an FASTIS-associated transcriptomic profile that overlaps between ACC and FASN inhibitors yet differs significantly from that of other mechanistically diverse TIS inducers, including bleomycin, alisertib, doxorubicin, and palbociclib. The FASTIS phenomenon is a therapeutic outcome through which cancer cells adapt to survive clinical-grade lipogenesis inhibitors. The cholesterol-addicted FASTIS fate can be rationally exploited as a collateral sensitivity in "one-two punch" senogenic-(immuno)senolytic strategies.

A transcriptional signature associated with SARM sensitivity was identified, primarily driven by proliferation-related processes, consistent with a significant decrease in S-phase cell cycle proteins upon treatment in EP0062-sensitive models. In some EP0062-resistant tumors, the combination with palbociclib enhanced the antitumor effect of EP0062, suggesting a potential strategy for metastatic patients with acquired ET resistance.

We retrospectively analyzed 332 patients with hormone receptor-positive/HER2-negative metastatic breast cancer who received first-line ribociclib or palbociclib plus endocrine therapy between 2018 and 2023. These findings suggest a potential association between BMI and clinical outcomes in this treatment setting. Prospective studies that integrate body composition and pharmacokinetics are required for validation.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, ribociclib, and palbociclib, are used in combination with ET as a standard of care first-line option in HR+, HER2- advanced disease to improve survival outcomes...Abemaciclib has also been shown to be effective when combined with a variety of ET options, including aromatase inhibitors, tamoxifen, fulvestrant, imlunestrant, or as monotherapy, and has shown efficacy regardless of prior CDK4/6 inhibitor exposure, ESR1 or PI3K pathway mutational status, menopausal status, and in both endocrine-sensitive and endocrine-resistant breast cancer. Importantly, the safety profile of abemaciclib has been consistent across trials and allows the administration of the drug over long periods of time when needed, particularly if dose-reduction strategies are employed. Together, the data summarized in this publication help inform clinical decision making regarding the role of abemaciclib in the treatment of patients with both early and metastatic HR+, HER2- breast cancer.

Six cycles of systemic chemotherapy with epirubicin and cyclophosphamide at three-week intervals were administered, followed by endocrine therapy with letrozole. Almost four years later, palbociclib became available and it was added to the patient's treatment...As this is a single-case clinical observation, any conclusions have limited generalizability. Given the rarity of primary metastatic ulcerative breast cancer there are no specific evidence-based treatment guidelines available and published studies have high heterogeneity and low level of evidence, necessitating multidisciplinary approach on a case-by-case basis.

P1/2, N=435, Active, not recruiting, Stemline Therapeutics, Inc. | Recruiting --> Active, not recruiting

PADMA is the first randomized multicenter study to show that palbociclib + ET as first-line treatment compared with CT also leads to improvements in TTF and PFS in predominantly postmenopausal patients with HR-positive/HER2-negative mBC.