Ibrance (palbociclib)

P=N/A, N=1, Completed, Pfizer | Active, not recruiting --> Completed | N=580 --> 1 | Trial completion date: Aug 2024 --> Apr 2024 | Trial primary completion date: Aug 2024 --> Apr 2024

Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation.

P=N/A, N=688, Completed, Pfizer | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Feb 2024 | Trial primary completion date: Aug 2023 --> Feb 2024

P2, N=49, Active, not recruiting, National Cancer Institute (NCI)

There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC.

Curcumin alone led to dose-dependent responses and when combined with BYL719, positive effects were revealed, as they were when it was combined with MK-1775 or PD-0332991, suggesting a potential use of some of these combinations for HPV+ OPSCC.

In 2L, 12 of the 21 (57.1%) patients received CDK4/6i + ET, of which 58.3% received abemaciclib. The two-year overall survival (95% CI) was 97.4% (92.4, 100.0), and the median (range) follow-up was 28.7 (3.4-67.6) months. Despite the limitations inherent in real-world studies and a limited number of patients, these AI-extracted data complement previous studies, demonstrating the effectiveness of CDK4/6i + ET in the Canadian real-world 1L, with most patients receiving palbociclib as CDK4/6i in 1L.

As a monotherapy, palbociclib has been shown to decrease the expression of MDR-1 in doxorubicin-resistant cells, and when used in combination with doxorubicin, it has been shown to increase the accumulation of doxorubicin in the cell and consequently induce apoptosis. This is the first report that proposes the Palbociclib as a candidate for combination therapy to limit the Doxorubicin resistance in different cancer origins in clinics.

P1/2, N=1126, Recruiting, Amgen | Trial primary completion date: Sep 2026 --> Dec 2026

Clinical Trial Registration Number: NCT02448420

P3, N=500, Not yet recruiting, AstraZeneca

Although the AEs of palbociclib and abemaciclib affected the treatment considerably, the treatment duration and RDI were similar. CDK4/6 inhibitors should be selected based on the tolerability and manageability of each AE.

P3, N=500, Not yet recruiting, American Society of Clinical Oncology

The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

P1/2, N=15, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2025 --> Apr 2024

P2; Active, not recruiting --> Completed

Although grade 3-4 toxicity and dose reductions occurred frequently, most were expected and managed by dose reductions, showing that palbociclib is generally well tolerated and thus represents a valuable treatment option in the older population.

P2, N=550, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Overall, GSS offers a framework for better understanding of correlation between senescence and GC, which might provide new insights into the development of novel therapeutics in GC.

In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to positive controls Palbociclib, with GI50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 were the most potent compounds against CDK6/cyclin D3 kinase, with IC50 values of 0.135±0.041 μM, its activity is about 1/3 of the positive control Palbociclib.

We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.

P1/2, N=36, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Palbociclib+letrozole was the most frequently prescribed treatment (36.8%). Most patients presented hematologic toxicity but to a low degree. The probability of survival increases with treatment.

This review provides key background information on the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Additionally, special consideration should be given to populations at higher risk for polypharmacy, such as older patients with greater comorbidities. These interactions and patient characteristics should be considered when developing individual treatment plans with CDK4/6 inhibitors.

P2, N=47, Recruiting, City of Hope Medical Center | Active, not recruiting --> Recruiting | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

Deve-lopment of selective CDK4/6 inhibitors including palbociclib revolutionized the treatment of advanced HR+/HER2- breast cancer...There is now emerging evidence that the increased cell size is a cause rather than consequence of the cell cycle arrest. This review aims to summarize recent advances in our understanding of senescence induction, in particular that resulting from treatment with CDK4/6 inhibitors.

As palbociclib has been approved by the FDA for the treatment of breast cancer, these findings demonstrate the sensitivity of DSRCT to palbociclib and support immediate clinical investigation of palbociclib for treating this aggressive pediatric cancer. EWSR1::WT1 is essential for desmoplastic small round cell tumors and upregulates the cyclin D-CDK4/6-RB axis that can be targeted with palbociclib, providing a targeted therapeutic strategy for treating this deadly tumor type.

Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

P3, N=20, Terminated, Hoffmann-La Roche | Completed --> Terminated; The decision to not open the Phase III portion was based on a strategic sponsor decision and not driven by any safety concerns.

P=N/A, N=150, Recruiting, Fudan University

P=N/A, N=28, Completed, Pfizer | Active, not recruiting --> Completed | N=42 --> 28 | Trial completion date: Nov 2025 --> Sep 2023 | Trial primary completion date: Nov 2025 --> Sep 2023

P=N/A, N=1170, Completed, Pfizer | Recruiting --> Completed

Gedatolisib plus palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of-care therapies and had an acceptable safety profile.

These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men.

In HPV-negative HNSCC, CDK4/6 inhibitor shows promising anti-tumor effects, which exhibits a synergistic effect when combined with EGFR inhibitor only in specific drug concentration and mouse model.

In this systematic review, data from RCTs showed that palbociclib was effective, well tolerated, and maintained QoL in older patients with HR+/HER2- a/mBC. Palbociclib treatment in older patients in real-world settings was associated with similar clinical benefit as in RCTs.

Furthermore, the clinical-grade CDK4/6 inhibitor palbociclib exhibited a potent anti-tumor effect in xenograft mouse models, especially when combined with gemcitabine. In summary, our study firmly establishes MYC as an oncogene with prognostic significance in ENKTL and highlights CDK4 inhibition as a promising therapeutic strategy for treating ENKTL with MYC overexpression.

P1, N=31, Active, not recruiting, Eisai Inc. | Trial completion date: Mar 2024 --> Aug 2024

P1, N=256, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting

Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

P=N/A, N=1939, Completed, Pfizer | Recruiting --> Completed | Trial completion date: Mar 2024 --> Nov 2023 | Trial primary completion date: Mar 2024 --> Nov 2023

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Jul 2024