Comparative efficacy of different targeted therapies plus fulvestrant for advanced breast cancer following progression on prior endocrine therapy: a network meta-analysis

Zhang, Tingting; Feng, Fubin; Wei, Zhao; Yao, Yan; Tian, Jinhui; Zhou, Chao; Zang, Chuanxin; Liu, Cun; Wang, Xue; Sun, Changgang

doi:10.2147/cmar.s176172

Cited by 12 publications

(13 citation statements)

References 45 publications

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“…Most of the published network meta-analyses assessing the efficacy of ET-based regimens in HR+/HER2− advanced breast cancer only included patients with endocrine-sensitive, [71][72][73] or with endocrine-resistant disease. [74][75][76] Of the network meta-analyses that have included both groups of patients, one specifically compared palbociclib+ET to different single-agent ET, 77 another compared everolimus+exemestane to several chemotherapy regimens 78 and the third evaluated palbo-ciclib+ET versus chemotherapy, 79 making them difficult to compare with our results. Another recent and very large network meta-analysis has evaluated all chemotherapy and ET-based treatments in postmenopausal women with HR+/HER2− metastatic breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis

et al. 2020

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BackgroundSeveral endocrine therapy (ET)-based treatments are available for patients with advanced breast cancer. We assessed the efficacy of different ET-based treatments in patients with hormone receptor-positive/HER2-negative advanced breast cancer with endocrine-sensitive or endocrine-resistant disease.MethodsWe searched Medline and Cochrane Central Register of Controlled Trials up to 15 October 2019 and abstracts from major conferences from 2016 to October 2019. We included phase II/III randomised trials, comparing ≥2 ET-based treatments. Progression-free survival (PFS) and overall survival (OS) were analysed by network meta-analyses using MTC Bayesian models based on both fixed-effect and random-effect models; relative treatment effects were measured as HRs and 95% credibility intervals (CrI). All statistical tests were two-sided. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and this systematic review is registered in the PROSPERO database.Results55 publications reporting on 32 trials (n=12 293 patients) were included. Regarding PFS in the endocrine sensitive setting (n=5200; 12 trials), the combination of cyclin-dependent kinases (CDK)4/6-inhibitors (CDK4/6i)+fulvestrant 500 mg (F500) was likely the most effective treatment (surface under the cumulative ranking curve (SUCRA)=97.3%), followed by CDK4/6i+aromatase inhibitor ±goserelin; there was no significant difference between them (HR 0.82; 95% CrI 0.54–1.25). Regarding OS (n=2157; five trials), the most effective treatment was probably CDK4/6i+F500 (SUCRA=97.3%); comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.63–0.95). Regarding PFS in the endocrine-resistant setting (n=6635; 20 trials), CDK4/6i+F500 was likely the most effective treatment (SUCRA=95.7%), followed by capivasertib+F500, without significant difference between them (HR 0.91; 95% CrI 0.60–1.36). For OS (n=4377; 11 trials), the most effective treatments were capivasertib+F500 (SUCRA=84.7%) and CDK4/6i+F500 (SUCRA=69.9%). Comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.67–0.89).ConclusionsCDK4/6i+F500 is likely the best treatment option in both endocrine-sensitive and endocrine-resistant diseases for PFS, and in endocrine-sensitive patients for OS. Concerning OS in endocrine-resistant patients, capivasertib+F500 and CDK4/6i+F500 are likely the best treatments.PROSPERO registration numberCRD42018104628.

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Section: Discussionmentioning

confidence: 99%

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis

et al. 2020

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“…This broad range of targets is the mechanistic basis for the antiproliferative and antiangiogenic effects of dovitinib observed in preclinical studies [6][7][8]. In the clinic, dovitinib has demonstrated promising activity in a number of cancers, including as a single agent in gastrointestinal stromal tumors [9] and in combination with fulvestrant in advanced breast cancer [10].…”

Section: Research Papermentioning

confidence: 97%

A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies

et al. 2020

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Background: Receptor tyrosine kinases (RTKs) play key roles in tumorigenesis. The multi-RTK inhibitor dovitinib has demonstrated promising antitumor activity in multiple cancers. Patients and Methods: In this phase 2, open-label, single-arm study, patients with advanced malignancies with RTK-pathway genetic aberrations whose disease progressed on/following standard treatment received dovitinib (500 mg/day; 5-dayson/2-days-off). The primary endpoint was clinical benefit rate (CBR; complete response, partial response [PR], or stable disease [SD] for ≥ 16 weeks). Results: Of 80 patients enrolled, common tumors included gastrointestinal stromal tumors (GIST; 20.0%), colorectal cancer (CRC; 18.8%), and ovarian cancer (10.0%). Patients were heavily pretreated (median prior lines = 4; 67.5% had ≥ 3 prior lines). Genetic aberrations included cKIT (28.8%), FGFR3 (15.0%), and RET (15.0%). The CBR was 13.8%; one PR (GIST) and 10 SD (adenoid cystic [n = 3]; ovarian [n = 3]; GIST [n = 2]; CRC [n = 1]; gastroesophageal junction [n = 1]). The most common treatment-related adverse events were fatigue, diarrhea, nausea, and vomiting. Conclusions: In this heterogeneous patient population, the safety profile was acceptable for dovitinib therapy. A subset of patients with RTK pathway-activated tumors experienced clinical benefit. However, the primary endpoint was not met, suggesting further refinement of predictive biomarkers is required.

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“…The oral highly selective CDK inhibitors like palbociclib, ribociclib which are approved the treatment of hormone receptor-positive HR + /HER2-or metastatic breast cancer, and recent studies suggest that palbociclib significantly improved clinical outcome when combined with letrozole as primary endocrine-based treatment in post-menopausal women or fulvestrant women with disease progression following an endocrine therapy. Also, abemaciclib which has the favorable effects of on prolonging survival of breast cancer patients have also been observed in clinical trials both for single-agent and combination strategy represent an important therapeutic advancement in breast oncology [19,20].…”

Section: Cyclin Dependent Kinasementioning

confidence: 99%

Highlights on Specific Biological Targets; Cyclin-Dependent Kinases, Epidermal Growth Factor Receptors, Ras Protein, and Cancer Stem Cells in Anticancer Drug Development

Hawash

2019

Drug Res (Stuttg)

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Cancer is the second leading cause of death in worldwide, because of that we need a great effort to discover, determine and understand the main pathways and mechanism of action of new novel anticancer drugs, which highly selective on the cancerous cells over the normal cells. The traditional approaches to the treat cancer depend on surgery, radiotherapy, and chemotherapy, according to the medicinal reports the chemotherapy is still the main procedure in the cancer cure or treatment till nowadays, and it is one of the main factors that drops the mortality of cancer in the last years. In the past decades the chemotherapeutic agents were used in the cancer treatment without clear understand on which target, protein, or enzyme that is working, and it was making the inhibition on the whole family of enzymes or receptors which lead to high toxicity and side effects, but nowadays the anticancer agents work with high selectivity on specific subtype of clear targets, and these targets usually present in high percentage in the cancerous cells. In this review article we will summarize some of these specific targets for anticancer drugs like Cyclin-dependent kinases (CDKs), epidermal growth factor receptors (EGFR), Ras protein, and Cancer stem cells, finally, we will mention some anticancer drugs which approved by FDA in 2018 which work on specific targets.

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Comparative efficacy of different targeted therapies plus fulvestrant for advanced breast cancer following progression on prior endocrine therapy: a network meta-analysis

Cited by 12 publications

References 45 publications

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis

A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies

Highlights on Specific Biological Targets; Cyclin-Dependent Kinases, Epidermal Growth Factor Receptors, Ras Protein, and Cancer Stem Cells in Anticancer Drug Development

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