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

Brandão, Mariana; Maurer, Christian; Ziegelmann, Patrícia Klarmann; Pondé, Noam; Ferreira, Arlindo R.; Martel, Samuel; Piccart, Martine; Azambuja, Evandro de; Debiasi, Márcio; Lambertini, Matteo

doi:10.1136/esmoopen-2020-000842

Cited by 19 publications

(13 citation statements)

References 47 publications

(62 reference statements)

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“…The cyclin‐dependent kinase (CDK) is a family of molecules that play a key role in the control of cell division and represent an important therapeutic target. Selective CDK4/6i have been approved for the treatment of patients with HR+/HER2‐negative (HER2‐) metastatic BC and are now the standard of care in first line, and a valid option in second or further lines in combination with endocrine therapy 25,26 . The CDK4/6i abemaciclib has been also FDA‐approved as monotherapy in patients with HR+/HER2‐ metastatic BC with disease progression to endocrine therapy and prior chemotherapy in the metastatic setting 27 .…”

Section: Cdk4‐6 Inhibition In Her2‐positive Breast Cancermentioning

confidence: 99%

CDK4/6 and PI3K inhibitors: A new promise for patients with HER2‐positive breast cancer

Agostinetto

Debien

Marta

et al. 2021

Eur J Clin Investigation

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Background HER2‐positive (HER2+) breast cancer represents a heterogeneous breast cancer subtype, including both oestrogen receptor (ER) positive and negative tumours. A deeper understanding of the crosstalk between ER and HER2 receptor pathways has led to the development of treatment strategies consisting of a simultaneous blockade of both signalling pathways, as a reasonable approach to prevent the onset of mechanisms of resistance. Methods This review was based on the material searched on PubMed, MEDLINE and Embase databases and on conference proceedings from major oncology conferences up to 15 December 2020. The search strategy included the following keywords: ‘HER2‐positive breast cancer’, ‘CDK4‐6 inhibitors’ and ‘PI3K inhibitors’, and was adapted for use with different bibliographic databases. Results CDK4/6 and PI3K inhibitors are two classes of agents already approved in patients with hormone receptor positive, HER2‐negative breast cancer. Recently, promising data with their use have been also shown in HER2+ disease. Results from preclinical and clinical studies are shedding light on the role of these classes of agents in HER2+ breast cancer, and are paving the road for a forthcoming change in clinical practice. Conclusions Treatment landscape for HER2+ breast cancer is rapidly changing, and CDK4/6 and PI3K inhibitors represent a new promising strategy to improve patients’ outcomes.

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Section: Cdk4‐6 Inhibition In Her2‐positive Breast Cancermentioning

confidence: 99%

CDK4/6 and PI3K inhibitors: A new promise for patients with HER2‐positive breast cancer

Agostinetto

Debien

Marta

et al. 2021

Eur J Clin Investigation

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“…CDK4/6 inhibitors (CDK4/6is) have been approved for the treatment of patients with HRþ/HER2À locally advanced and metastatic BCs, and are now the standard of care in first line, and also a valid treatment option in second line, in combination with ET. 4,5 With the aim to assess the efficacy of CDK4/6is at earlier treatment lines, several ongoing studies, focusing on different populations and with differing treatment strategies, are currently evaluating the addition of CDK4/6is to adjuvant ET for patients with HRþ/HER2À EBC. Thus far, results from these studies have been heterogenous, and therefore the role of CDK4/6is in EBC has been the topic of an intense academic discussion.…”

Section: Introductionmentioning

confidence: 99%

CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

et al. 2021

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Background: The combination of cyclin-dependent kinases 4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is standard of care for patients with hormone receptor-positive (HRþ), HER2-negative (HER2À) advanced breast cancer (BC). However, studies evaluating adjuvant CDK4/6is provided contradictory results thus far. Materials and methods: We conducted a systematic review and meta-analysis to assess if the addition of CDK4/6is to adjuvant ET impacts on survival's outcomes and safety of patients with HRþ/HER2À early BC (EBC). This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and was registered in the PROSPERO database (ID: CRD42020218597). A systematic review of PubMed, Cochrane and EMBASE databases and major conference proceedings was performed up to 15 December 2020. All randomized controlled trials including patients with HRþ/HER2À EBC treated with CDK4/6is plus ET versus ET alone in the adjuvant setting were included. Pooled hazard ratios (HRs) and odds ratios (ORs) for survival and safety outcomes, respectively, were calculated with 95% confidence intervals (95% CIs) using random effect models. Results: With data available from three studies (N ¼ 12 647), the addition of CDK4/6is to adjuvant ET showed a trend for a benefit in terms of invasive disease-free survival (IDFS; HR 0.85, 95% CI 0.71-1.01; P ¼ 0.071). No significant improvement in distant relapse-free survival was observed (HR 0.83, 95% CI 0.58-1.19; P ¼ 0.311). The risk of allgrade toxicities and early treatment discontinuation increased significantly with the addition of CDK4/6is to ET (OR 9.36, 95% CI 3.46-25.33, P < 0.001, and OR 22.11, 95% CI 9.45-51.69, P < 0.001, respectively). Conclusion: The administration of adjuvant CDK4/6is to patients with HRþ/HER2À EBC showed a trend for an IDFS benefit and an increase in the risk of toxicities and treatment discontinuation. The role of adjuvant CDK4/6is remains controversial and a longer follow-up of these randomized controlled trials is needed before supporting a straightforward change in clinical practice.

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“…In fact, we previously demonstrated the absence of significant difference between ET + TT and chemotherapy and the clear superiority of ET combined with novel CDK4/6-inhibitors (CDK4/6i) or PIK3CA/mTOR axis inhibitors compared to standard ET, in terms of both response rates and progression-free survival (PFS) [ 19 ]. However, previous network meta-analyses comparing all first-/second-line treatment options [ 19 , 20 , 21 , 22 ] were unable to evaluate the efficacy of these novel treatment strategies in specific clinical subsets (endocrine-resistant or endocrine-sensitive patients, patients with visceral or bone-only disease, pre-menopausal patients, etc.) and did not provide overall survival (OS) data.…”

Section: Introductionmentioning

confidence: 99%

Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis

Schettini

Giuliano

Giudici

et al. 2021

Cancers

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A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) ± target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making.

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

Cited by 19 publications

References 47 publications

CDK4/6 and PI3K inhibitors: A new promise for patients with HER2‐positive breast cancer

CDK4/6 and PI3K inhibitors: A new promise for patients with HER2‐positive breast cancer

CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis

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