A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program DOI Creative Commons
Carlo Palmieri,

A. E. Musson,

Catherine Harper‐Wynne

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(5), P. 852 - 860

Published: July 19, 2023

The Ibrance® Patient Program was established to provide access palbociclib for UK National Health Service (NHS) patients with metastatic breast cancer (MBC), pending a funding decision.Non-interventional cohort study involving retrospective medical record review of commenced on between April and December 2017 at eight centres. Primary outcomes included clinicopathological characteristics, treatment patterns, clinical selected adverse events.Overall, 191 were identified, median age 57.0 years (range 24.3-90.9); 30% diagnosed de novo MBC; 72% received first-line 10% as ≥ second-line treatment. Median progression-free survival (95% CI) 22.8 months (16.5-not reached [NR]) in first-line; NR 7.8 (6.8-NR) (median follow-up: 24 months). overall (OS) the cohort; OS rate 74.2% (67.1-81.9%) 82.1% (72.6-92.8%) 55.0% (37.0-81.8%) second-line. Forty-seven per cent developed grade 3-4 neutropenia; 3% febrile neutropenia.This supports effectiveness demonstrates benefit early schemes that bridge gap regulatory approval NHS new medicines.Clinical trial: ClinicalTrial.gov:NCT03921866.

Language: Английский

Efficacy of CDK4/6 inhibitors combined with endocrine therapy in HR+/HER2− breast cancer: an umbrella review DOI Creative Commons

Dongqing Pu,

Debo Xu,

Yue Wu

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(1)

Published: Jan. 1, 2024

The use of Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors has profoundly changed the challenge endocrine therapy (ET) resistance in hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer. However, there is currently no comprehensive evaluation evidence for efficacy CDK4/6 inhibitors. We conducted an umbrella review to explore impact inhibitor combined with ET on cancer by summarizing assessing meta-analysis (MA) systematic (SR) evidence.

Language: Английский

Citations

7
Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials DOI Open Access
Francisco Cézar Aquino de Moraes, Gustavo de Oliveira Almeida,

Vinícius Freire Costa Alves

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(5), P. 464 - 464

Published: April 27, 2024

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2−) early-stage (esBC) is still to be confirmed. Methods: We performed a systematic review and meta-analysis investigate the CDK4/6i esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free (DRFS), overall (OS). only phase III randomized controlled trials. used RStudio version 4.2.3, we considered p < 0.05 statistically significant. Results: Four studies were selected, including 14,168 patients, which 7089 treated 7079 received monotherapy. Regarding patient characteristics, 6828 (48.2%) premenopausal. Compared alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; = 0.034) significantly favor ET. However, there no significant differences DRFS 0.79; 0.58, 1.07; 0.132) nor OS 0.96; 0.69, 1.35; 0.829). Conclusions: Our results show that addition associated benefit HR+/HER2− esBC patients iDFS. More longer follow-up needed assess benefits.

Language: Английский

Citations

6
Targeting KRAS in Colorectal Cancer: A Bench to Bedside Review DOI Open Access
Fernand Bteich, Mahshid Mohammadi,

T. Li

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12030 - 12030

Published: July 27, 2023

Colorectal cancer (CRC) is a heterogeneous disease with myriad of alterations at the cellular and molecular levels. Kristen rat sarcoma (KRAS) mutations occur in up to 40% CRCs serve as both prognostic predictive biomarker. Oncogenic KRAS protein affect proliferation survival, leading tumorigenesis through RAS/MAPK pathways. Until recently, only indirect targeting pathway had been investigated. There are now several allele-specific inhibitors late-phase clinical trials, many newer agents strategies undergoing preclinical early-phase testing. The adequate treatment KRAS-mutated CRC will inevitably involve combination therapies due existence robust adaptive resistance mechanisms these tumors. In this article, we review most recent understanding findings related CRC, inhibitors, well evolving for patients.

Language: Английский

Citations

14
Targeting sex steroid biosynthesis for breast and prostate cancer therapy DOI
Matti Poutanen, Malin Hagberg Thulin, Pirkko Härkönen

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(10), P. 686 - 709

Published: Sept. 8, 2023

Language: Английский

Citations

12
mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation DOI Creative Commons
Ye Hu, Fengxi Chen, Siwen Sun

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 25, 2024

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients HER2-low metastatic breast cancer (MBC). We performed a systematic review investigate treatment concept field MBC utilized series cases identified literature illustrate concept. Here we reported two clinical whose disease progressed after prior MTAs such as docetaxel vincristine. When rechallenged disitamab vedotin ((RC48-antibody-drug conjugate (ADC), monomethyl auristatin (MMAE) MTA)), both achieved partial response final progression-free survival (PFS) was 13.5 9 months, respectively. Genomic profiling detected PIK3CA H1047R mutation patients. The were treated everolimus before being RC48, which may lead better response. further summarizes analyzes mechanism PI3K-AKT signaling pathway MTA resistance reveals that be molecular marker for prediction mTOR inhibitors, providing new insights therapeutic strategies application

Language: Английский

Citations

4
Oral SERDs alone or in combination with CDK 4/6 inhibitors in breast cancer: Current perspectives and clinical trials DOI Open Access

Kleoniki Apostolidou,

Eleni Zografos,

Maria Alkistis Papatheodoridi

et al.

The Breast, Journal Year: 2024, Volume and Issue: 75, P. 103729 - 103729

Published: April 4, 2024

Over the past few decades, first-line therapy for treating advanced and metastatic HR+/HER2-breast cancer has transformed due to introduction of adjuvant endocrine with cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). However, there is an unmet need novel classes superior efficacy improve treatment outcomes overcome CDK4/6i resistance. New generation selective estrogen receptor degraders (SERDs), orally administered higher bioavailability, could potentially be compounds meet this emerging need. In paper, we review accredited clinical studies on combining effects CDK4/6 oral SERDs, report data when available, provide a framework future research focusing these promising agents.

Language: Английский

Citations

4
Molecular changes driving low-grade serous ovarian cancer and implications for treatment DOI Creative Commons
Lucy Kelliher, Roni Yoeli‐Bik, Lisa Schweizer

et al.

International Journal of Gynecological Cancer, Journal Year: 2024, Volume and Issue: 34(10), P. 1630 - 1638

Published: July 1, 2024

Low-grade serous ovarian cancer was previously thought to be a subtype of high-grade cancer, but it is now recognized as distinct disease with unique clinical and molecular behaviors. The may arise de novo or develop from borderline tumor. Although more indolent than most patients have advanced metastatic at diagnosis recurrence common. Recurrent low-grade often resistant standard platinum–taxane chemotherapy, making difficult treat the options currently available. New targeted therapies are needed, their development contingent on deeper understanding specific biology disease. known drivers tumors strong hormone receptor expression, mutations in mitogen-activated protein kinase (MAPK) pathway (KRAS, BRAF, NRAS), genes related MAPK (NF1/2, EIF1AX, ERBB2). However, inhibitors shown only modest responses. Based discovery CDKN2A cyclin-dependent kinases 4 6 (CDK4/6) being tested trials combination therapy. Additional seen smaller population include USP9X, ARID1A, PIK3CA, no targeting them been clinically. This review summarizes clinical, pathologic, features they understood introduces potential therapeutic targets new avenues for research.

Language: Английский

Citations

4
A Canadian real-world, multi-center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2-negative advanced breast cancer DOI Creative Commons
Catherine Doyle, Ana Elisa Lohmann,

Nayyer Iqbal

et al.

Breast Cancer Research and Treatment, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Language: Английский

Citations

0
A novel formula to improve the accuracy and prognostic ability of determining the survival time after recurrent breast cancer DOI
Reiki Nishimura, Yasuaki Sagara,

Reiko Mitsueda

et al.

Breast Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Language: Английский

Citations

0
Association between trastuzumab treatment interruption and survival in HER2-positive metastatic breast cancer patients: a retrospective study DOI
Ludmila Andrade Alves Ferreira, Mário Jorge Sobreira da Silva, Patrícia Ribeiro Portella de Araújo

et al.

Journal of Chemotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: April 2, 2025

This retrospective study analyzed the effect of trastuzumab treatment interruption on overall survival (OS) and progression-free (PFS) within two years after diagnosis in women with HER2-positive metastatic breast cancer. Sociodemographic, clinicopathological, therapeutic variables were collected from medical records patients diagnosed between 2013 2017 at a comprehensive cancer care center Brazil. Survival estimates performed using Kaplan-Meier method log-rank test. The Cox Regression model was used to estimate risk outcomes. average OS 20.2 months, PFS 13.1 months. Interruption associated an increase time compared continued (22.5 months; 95% CI: 21.8 - 23.3 vs. 17.7 15.9 19.4; P = 0.001). adjusted revealed that therapy independently 2.86-fold increased mortality.

Language: Английский

Citations

0