Efficacy of PI3K inhibitors in advanced breast cancer

Cortés, Javier; Bachelot, Thomas; Varga, Andrea; Arnedos, Mónica

doi:10.1093/annonc/mdz381

Cited by 166 publications

(142 citation statements)

References 95 publications

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“…Recent SOLAR-1 trial leading to FDA approval of the first PI3K inhibitor, alpelisib in combination with Fulvestrant, has revolutionized BC therapy for postmenopausal women and men with HR+/HER2-, PIK3CA mutated advanced or metastatic BC's which have progressed on or after endocrine therapy. Combination of alpelisib with fulvestrant showed that the specificity of alpelisib against the p110α catalytic isoform provided additional efficacy and a better toxicity profile [ 48 ]. The finding is very important in our cohort which was dominated by HR+ive cases and HR+ive HER2-ive patients with alteration in PI3KCA/AKT/PTEN as common genetic event.…”

Section: Discussionmentioning

confidence: 99%

Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

Ghosh

Naik

Lingaraju

et al. 2021

Translational Oncology

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Breast cancer (BC) is a heterogeneous disease. Numerous chemotherapeutic agents are available for early stage or advanced/metastatic breast cancer to provide maximum benefit with minimum side effects. However, the clinical outcome of patients with the same clinical and pathological characteristics and treated with similar treatments may show major differences and a vast majority of patients still develop treatment resistance and eventually succumb to disease. It remains an unmet need to identify specific molecular defects, new biomarkers to enable clinicians to adopt individualized treatment for every patient in terms of endocrine, chemotherapy or targeted therapy which will improve clinical outcomes in BC. Our study aimed to identify frequent hotspot mutation profile in BC by targeted deep sequencing in cancer-related genes using Illumina Truseq amplicon/Swift Accel-Amplicon panel and MiSeq technology in an IRB-approved prospective study in a CLIA compliant laboratory. All the cases had pathology review for stage, histological type, hormonal status and Ki-67. Data was processed using Strand NGS™. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis.

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Section: Discussionmentioning

confidence: 99%

Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

Ghosh

Naik

Lingaraju

et al. 2021

Translational Oncology

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“…Many preclinical models have been used to attempt to elucidate the mechanisms of endocrine resistance. At present, researchers have established that disorder of the PI3K/AKT/mTOR axis and CDK/Rb/E2F pathway is the critical mechanism leading to endocrine resistance [ 64 ] In this meta-analysis, fulvestrant combined with palbociclib, abemaciclib, alpelisib, buparlisib, everolimus, or capecitabine showed efficacy in prolonging PFS for patients with ET resistance compared with fulvestrant alone. Although there was no significant difference between the 2 PI3K inhibitors, the efficacy of alpelisib was slightly better than that of buparlisib.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Network Meta-Analysis

Liu

Sun

et al. 2020

J Breast Cancer

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We aimed to explore what kind of endocrine treatments are optimal for hormone receptor-positive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

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“…PIK3CA mutations represent one of the most frequent genetic aberrations in luminal breast cancer and were shown to be associated with a favorable prognosis. However, PIK3CA-mutated HER2-positive breast cancer was demonstrated to be associated with worse prognosis [20]. The frequency of these mutations and the biological relevance of the pathway render PIK3CA a promising therapy target.…”

Section: Molecular Profiling Of Advanced Breast Cancermentioning

confidence: 99%

Molecular profiling in breast cancer—ready for clinical routine?

Tendl

Bagó-Horváth

2020

memo

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The herald of genomic testing opened novel diagnostic and therapeutic possibilities for many tumor entities. For breast cancer, molecular profiling has become an integral part of disease management on multiple levels. Genetic testing allows for the identification of hereditary cancer syndromes in patients with a family history of malignancies and contributes to the successful prevention of breast cancer. In early breast cancer, several prospective randomized trials demonstrated the prognostic significance of commercially available mRNA-based gene expression analyses, which now have become part of standard of care in the adjuvant setting. In advanced breast cancer, testing for targetable mutations ensures personalized cancer treatment. Poly-ADPribose polymerase (PARP) inhibitors provide the first targeted alternative for patients with BRCA 1/2-associated breast cancer. In advanced breast cancer of luminal type, the detection of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutations provides a novel treatment option with alpelisib, a PIK3CA inhibitor. Further targetable mutations include NTRK3 in rare cases of secretory breast carcinoma and human epidermal growth factor receptor 2 (HER2). Recent data support the importance of the analysis of circulating tumor cells and cell-free DNA. These "liquid biopsies" open novel possibilities of molecular profiling. However, clinical benefit of such analyses remains to be confirmed.

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Efficacy of PI3K inhibitors in advanced breast cancer

Cited by 166 publications

References 95 publications

Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Network Meta-Analysis

Molecular profiling in breast cancer—ready for clinical routine?

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