Ibrance (palbociclib)

Moreover, dalpiciclib is being investigated in HR+/HER2- BC treatment. This article will summarize clinical efficacy, recommendations, and differences in toxicity profile between palbociclib, ribociclib, and abemaciclib and will also discuss the possibility of using dalpiciclib in the treatment of breast cancer.

In routine US clinical practice, palbociclib + AI was associated with significantly prolonged OS versus AI alone in 1L treatment of patients aged ≥ 65 years with de novo HR+/HER2- mBC, adding to the growing body of evidence on the survival benefit of palbociclib + AI in this patient population.

The study concluded that palbociclib did not significantly improve survival outcomes in the overall population. Exploratory post-hoc analyses suggested a trend towards better iDFS outcome in patients with lobular breast cancer receiving palbociclib.

In this real-world study, rwPFS in HR+/HER2- MBC patients was maintained irrespective of dose adjustments. However, dose adjustments were associated with extended treatment duration and OS.

Patients receiving ribociclib or palbociclib were evaluated for the development of ILD. The incidence of CDK4/6 inhibitor-associated ILD in Turkish breast cancer patients appears higher than previously reported in clinical trials. More robust, long-term studies are necessary to identify potential risk factors and mitigate ILD-related mortality.

Taken together, we describe CDK4/6i-dependent mechanisms resulting in early-onset resistance to CDK4/6i + ET, using clinically relevant drug concentrations, in preclinical breast cancer cell models. The characterization of these preclinical models post progression on CDK4/6 inhibitor + ET treatment highlights the potential that the specific sequencing of CDK4/6 inhibitors could offer to overcome acquired resistance to CDK4/6i + ET. Abemaciclib + fulvestrant is currently under clinical investigation in patients with HR+, HER2- breast cancer and progression on prior CDK4/6i + ET (NCT05169567, postMONARCH).

In the PALLAS trial, addition of palbociclib did not decrease adherence to adjuvant ET. Though numbers declined over time, daily adherence for palbociclib and ET remained relatively high at each cycle.

Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.

Elevated TK1 activity after six months of CDK4/6i and an increase in TK1 concentration from baseline to six months under CDK4/6i significantly correlated with a decreased PFS. These results indicate a possible value of TK1 concentration and activity before and during CDK4/6i for HR+/HER2- mBC patients to guide treatment that warrants further investigation.

P1/2, N=65, Recruiting, Tianjin Medical University Second Hospital

Materials and A retrospective analysis of 120 patients with HR+/HER2- MBC treated with ribociclib or palbociclib in combination with letrozole or fulvestrant was performed. In our study, while the mPFS was not statistically significant in both arms, the 3-year OS rate was higher in the ribociclib arm and statistically significant. Our findings were confirmed in randomized studies comparing both agents head-to-head.

This update included 82 unique studies, 42.7% for palbociclib, 7.3% for ribociclib, and 3.7% for abemaciclib; 46.3% assessed multiple CDK4/6i. These data are important to guide clinical decision-making, as they include patients who are not adequately represented in clinical trials. Studies with longer follow-up are needed to assess long-term benefits of all three CDK4/6i therapies in HR+/HER2- A/MBC.

Consistent with this observation, 18F-FLT PET was able to differentiate the resistance to Palbociclib from sensitivity to PF-06873600 (CDK2/4/6 inhibitor) and PF-07104091 in OVCAR-3 model. This work highlights the utility of 18F-FLT PET as a quantitative, non-invasive biomarker which provides whole-body information. 18F-FLT PET has potential to be a biomarker in novel CDK inhibitor clinical trials to evaluate Palbociclib resistance and identifying responding and non-responding patients.

P1, N=12, Completed, Children's Oncology Group | Active, not recruiting --> Completed

This case highlights the potential benefits of CDK4/6 inhibitors combined with endocrine therapy in the management of HR+, HER2-negative metastatic breast cancer, particularly in cases with skin involvement. These agents have reshaped the therapeutic landscape, providing prolonged disease control and improved patient outcomes.

P1, N=111, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2025 --> Dec 2027 | Trial primary completion date: Sep 2025 --> Dec 2027

We performed adisproportionality analysis to evaluate CDKI-related adverse events (AEs) inolder adults administered abemaciclib, palbociclib, and ribociclib. Our results aligned with clinicalobservations, emphasizing possible CDKI-related AEs. Conducting future clinicalresearch is essential to confirm AE-related differences among CDKIs in olderindividuals.

This extended follow-up analysis of PROs in PALOMA-2 shows continued QoL maintenance for patients with ER+/HER2- mBC receiving long-term palbociclib plus letrozole treatment.

P1, N=34, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2025 --> Dec 2025

Moreover, we showed that the CDK6 inhibitor palbociclib effectively suppresses the pro-growth and chemoresistant effects induced by IGF2BP3 overexpression. These results suggested that the IGF2BP3/m6A/CDK6 axis plays a pivotal role in bladder cancer progression and chemoresistance, and that targeting this pathway with CDK6 inhibitors such as palbociclib may offer a promising therapeutic strategy for overcoming cisplatin resistance in bladder cancer.

In patients with heavily pretreated metastatic RCC, abemaciclib monotherapy had no clinically meaningful activity without new toxicity signals. This data will offer important insight into interpretation of results for ongoing trials exploring CDK4/6 inhibition in combination with HIF-2α inhibitors and immunotherapy.

P2, N=96, Recruiting, Abramson Cancer Center at Penn Medicine | Trial primary completion date: Nov 2024 --> Jul 2027

Given the tumor's limited sensitivity to chemotherapy, she was treated with neoadjuvant endocrine therapy (ET) using fulvestrant, palbociclib, and leuprolide. This case supports the potential role of endocrine-based targeted therapy in managing pediatric LGSOC, offering a viable alternative for patients with limited treatment options. Further research is needed to optimize treatment strategies and improve survival outcomes in this rare population.

P=N/A, N=1443, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Mar 2029 --> Mar 2039

Replicative, mitotic, oxidative, and genotoxic forms of TIS were induced in p16-null/p53-proficient, BAX-deficient, and BRCA1-mutant cancer cells using mechanistically distinct TIS-inducing cancer therapeutics, including palbociclib, alisertib, doxorubicin, bleomycin, and olaparib...Furthermore, regardless of senescence-inducing therapeutic, stable/transient senescence acquisition, or genetic context, all TIS phenotypes shared a variable but significant senolytic response to the BCL-xL-selective BH3 mimetic A1331852. These findings may help to rethink the traditional assumption of the primed apoptotic landscape of TIS cancer cells. BCL-xL is a conserved anti-apoptotic effector of the TIS BCL2/BH3 interactome that can be exploited to maximize the efficacy of "one-two punch" senogenic-senolytic strategies.

P1, N=265, Active, not recruiting, Relay Therapeutics, Inc. | Trial completion date: Jul 2024 --> May 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

P3, N=405, Active, not recruiting, ETOP IBCSG Partners Foundation | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> Jan 2029 | Trial primary completion date: Jan 2025 --> Jan 2026

P2, N=220, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Jun 2025

P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Dec 2027

P=N/A, N=68, Active, not recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Mar 2021 --> Mar 2026

The sensitivity of three common drugs (homoharringtonine, lapatinib, and palbociclib) in LUAD could be evaluated by the CR-relevant risk model. Ultimately, the experimental results confirmed that the expression trends of CDK1 and HLA-DMA in our collected clinical samples were in line with the expression trends in the TCGA-LUAD dataset. In conclusion, a CR-relevant risk model based on CDK1 and HLA-DMA was constructed by using bioinformatics analysis, which might supply a new insight into the improved prognosis of LUAD.

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

The phase 2 NA-PHER2 trial (NCT02530424) investigated chemo-free preoperative HER2 blockade (trastuzumab + pertuzumab) and CDK4/6 inhibition (palbociclib) with or without endocrine therapy (fulvestrant) in HER2+ER+ breast cancer. The LowLow group exhibited a Luminal A phenotype by the end of treatment. This study expands our understanding of drivers and dynamics of HER2+ER+ tumour response, towards treatment tailoring.

P=N/A, N=36, Recruiting, Fudan University

P1, N=54, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Dec 2024 --> Aug 2025

In summary, zanidatamab has shown significant tumor response, progression-free survival, disease control, and improved quality of life in early trials, however, the lack of long-term safety and efficacy data remains a key limitation, requiring further research.

In the group with high CDH18 expression, the IC50 values for (5Z)-7-Oxozeaenol, AG-014699, CEP-701, Mitomycin C, PD-0325901, PD-0332991, PHA-665752, SL 0101-1, and SN-38 were notably elevated. CDH18 is a novel promising biomarker in UCEC, uniquely associating tumor progression, immune modulation, and chemotherapy resistance, offering enhanced prognostic accuracy and guiding individualized therapeutic strategies for improved patient outcomes.

P1, N=181, Active, not recruiting, Genentech, Inc. | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

Post-treatment analysis indicated a negative correlation between KNSTRN levels and the efficacy of CDK4/6i or combination therapy, whereas TRPC4AP levels positively correlated with treatment response. These findings offer critical insights into the mechanisms of PARPi resistance in EOC and suggest that combining PARPi with CDK4/6i is a promising therapeutic strategy to overcome this resistance and improve outcomes for patients with EOC.

P1/2, N=54, Recruiting, Memorial Sloan Kettering Cancer Center

Dose reduction had no impact on progression-free survival (PFS) (p = 0.114 for first-line treatment, p = 0.528 for second and subsequent-line treatment; p > 0.05). Regarding the absence of disparity in progression-free survival between patients with dose reduction and those without, dose reduction should not be avoided in certain patient groups to ensure therapy continuity and mitigate potential adverse effects.

We report herein real-world and preclinical evidence that ESR1 mutations, particularly Y537S and D538G, can drive resistance to CDK4/6 inhibitors.