Nature Cancer, Год журнала: 2025, Номер 6(1), С. 24 - 40
Опубликована: Янв. 30, 2025
Язык: Английский
Cancer Medicine, Год журнала: 2024, Номер 13(10)
Опубликована: Май 1, 2024
Abstract Background Cyclin‐dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard‐of‐care for patients with hormone receptor‐positive, human epidermal growth factor receptor‐2 negative (HR+/HER2−) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 remains unclear. This study aimed to evaluate efficacy and safety of abemaciclib switching ET versus chemotherapy prior palbociclib‐based in Chinese HR+/HER2− MBC. Methods From 414 consecutive MBC who had been treated palbociclib from September 2018 May 2022 Peking University Cancer Hospital, we identified 80 received or palbociclib, matched age, original stage at diagnosis, disease‐free interval, tumor burden 1:1 ratio. The primary endpoint was progression‐free survival (PFS) compared using Kaplan–Meier method. A Cox proportional hazard model performed identify clinical factors associated PFS group. Results median 6.0 months (95% confidence interval [CI]: 3.94–8.06) group 4.0 CI, 2.52–5.49) ( p = 0.667). And, there no difference between sequential nonsequential arm (6.0 vs. months) though fewer lines systemic longer arm. as first‐line a significantly ≥2nd‐line (11.0 5.0 months, 0.043). Based multivariable analysis, ER+/PR+ an independent PFS. There significant overall groups 0.069). Conclusion Our findings indicate that might be one feasible treatment options addition chemotherapy.
Язык: Английский
Процитировано
4
Heliyon, Год журнала: 2024, Номер 10(11), С. e31583 - e31583
Опубликована: Май 21, 2024
BackgroundIn recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged a new research focus in treatment hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. This network meta-analysis aimed to systematically evaluate efficacy and safety CDK4/6 inhibitors combined ET for HR+/HER2- cancer.MethodsA systematic search was conducted across PubMed, Web Science, Cochrane Library, GeenMedical databases identify randomized controlled trials investigating use The period spanned from inception each database up February 29, 2024. Data analysis using Stata 14.0 R 4.1.0 software.ResultsA total 20 (RCTs) were included this study, effectiveness four inhibitors—Abemaciclib, Dalpiciclib, Ribociclib, Palbociclib—when results indicated that Abemaciclib+ET, Dalpiciclib+ET, Palbociclib+ET, Ribociclib+ET exhibited similar therapeutic effects terms improving objective response rate (ORR), disease control (DCR) reducing occurrence fatigue, all which superior alone. However, prolonging progression-free survival (PFS) overall (OS), Dalpiciclib+ET significantly improved PFS compared Ribociclib+ET, Abemaciclib Palbociclib. OS Palbociclib+ET. Regarding adverse reaction events (AREs), had higher incidence Ribociclib+ET. neutropenia caused by Abemaciclib, Abemaciclib+ET demonstrated worst profile concerning diarrhea.ConclusionAbemaciclib+ET likely represents most effective option effects, but it is prone causing diarrhea fatigue. On other hand, demonstrates best exhibits poorest profile, particularly relation neutropenia. Therefore, clinicians should exercise increased vigilance monitoring managing when prescribing Dalpiciclib+ET.
Язык: Английский
Процитировано
4
Current Oncology, Год журнала: 2025, Номер 32(1), С. 53 - 53
Опубликована: Янв. 20, 2025
Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown. Methods: We conducted a systematic review and network meta-analysis (NMA) phase-II/-III randomized trials ER + MBC post CDK4/6i ET progression. calculated the hazard ratio (HR) for progression-free survival (PFS) overall (OS) using generic inverse variance odds ratios (ORs) Mantel–Haenszel method adverse events (AEs) with Review-Manager version-5.4. NMA was executed WINBUGS (Microsoft Excel). Three molecular subgroups were analyzed: HER2-low, PI3K/AKT/mTOR, ESR1 mutation subgroup selective receptor degrader (SERD). Results: A total 14 studies included. In HER2-low group, Sacituzumab govitecan trastuzumab deruxtecan had similar efficacy (HR, 95% CI): PFS (0.98; 0.63–1.43) OS (1.08; 0.76–1.55). PI3K/AKT/mTOR-altered cases, capivasertib superior to alpelisib (0.77; 0.53–1.12), (0.80; 0.48–1.35). SERDs worse versus ongoing CDK 4/6i (ribociclib). Conclusion: No therapy emerged as unequivocal choice in post-CDK domain unselected subgroups. population, different toxicity spectrum seen. AKT-altered tumors, less toxic than alpelisib. PROSPERO ID: CRD4202236412.
Язык: Английский
Процитировано
0
Опубликована: Янв. 28, 2025
The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy has revolutionized treatment for hormone receptor-positive (HR+) metastatic breast cancer. However, the emergence resistance in most patients often leads to discontinuation with no consensus on effective second-line therapies. therapeutic benefits maintaining CDK4/6i or incorporating CDK2 (CDK2i) after disease progression remain unclear. Here, we demonstrate that sustained therapy, either alone combined CDK2i, significantly suppresses growth drug-resistant HR + Continued induces a non-canonical pathway retinoblastoma protein (Rb) inactivation via post-translational degradation, resulting diminished E2F activity delayed G1 progression. Importantly, our data highlight CDK2i should be effectively suppress overcome resistance. We also identify cyclin E overexpression as key driver inhibition. These findings provide crucial insights into overcoming cancer, supporting continued use strategic incorporation improve outcomes.
Язык: Английский
Процитировано
0
Nature Cancer, Год журнала: 2025, Номер 6(1), С. 24 - 40
Опубликована: Янв. 30, 2025
Язык: Английский
Процитировано
0