First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2–Positive and Hormone Receptor–Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial

Rimawi, Mothaffar F.; Ferrero, Jean-­Marc; Haba-Rodríguez, Juan de la; Poole, Christopher; Placido, Sabino De; Osborne, C. Kent; Hegg, Roberto; Easton, Valerie; Wohlfarth, Christine; Arpino, Grazia

doi:10.1200/jco.2017.76.7863

Cited by 181 publications

(161 citation statements)

References 21 publications

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“…Results showed an improvement in PFS with the 3-drug combination (18.9 vs 15.8 months; HR, 0.65; 95% CI, 0.48-0.89). 108 Grade 3 or higher adverse events observed were higher with trastuzumab and pertuzumab versus pertuzumab alone (50% vs 39%). Of note, about half of women received induction therapy with a taxane for 18 to 24 weeks before the start of endocrine therapy.…”

Section: Systemic Therapy For Recurrent or Stage IV Hr-positive Her2mentioning

confidence: 90%

“…Of note, about half of women received induction therapy with a taxane for 18 to 24 weeks before the start of endocrine therapy. Based on the results of the PERTAIN trial, 108 the NCCN panel notes that if treatment was initiated with chemotherapy and trastuzumab plus pertuzumab and the chemotherapy was stopped, endocrine therapy may be added to the trastuzumab plus pertuzumab.…”

Section: Systemic Therapy For Recurrent or Stage IV Hr-positive Her2mentioning

confidence: 99%

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Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Gradishar

Anderson

Abraham

et al. 2020

Journal of the National Comprehensive Cancer Network

1,013

602

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Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.

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Section: Systemic Therapy For Recurrent or Stage IV Hr-positive Her2mentioning

confidence: 90%

Section: Systemic Therapy For Recurrent or Stage IV Hr-positive Her2mentioning

confidence: 99%

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Gradishar

Anderson

Abraham

et al. 2020

Journal of the National Comprehensive Cancer Network

1,013

602

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show abstract

“…1. Among the nine studies [13,20,[27][28][29][30][31][32][33] included in this study, a total of involving 3,374 cases, including 8 phase III trials and 1 phase II trial. Of the nine studies, there were four studies comparing lapatinib, three studies comparing pertuzumab, and two studies comparing trastuzumab.…”

Section: Eligible Studies and Inclusion Characteristicsmentioning

confidence: 99%

Review A meta-analysis of the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancers

Chen

Shen

et al. 2020

Preprint

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Background The purpose of this study was to analyze the efficacy and safety of additional anti-HER2 (human epidermal growth factor receptor 2)-targeting drugs in HER2-positive advanced breast cancers.Methods For this study, the following databases were searched for articles published from its inception until December 2019: PubMed, Web of Science, EBSCO, and Cochrane library, of which the main outcomes were the progression-free survival (PFS) and overall survival (OS).Results We conducted a meta-analysis and the results showed that additional anti-HER2-targeting drugs improved the HER2-positive advanced breast cancer patients’ PFS (HR: 0.66, p < 0.001), OS (HR: 0.77, p < 0.001), respectively. In terms of drug types, the efficacy of lapatinib was the most (HR: 0.53, 95% Cl: 0.39–0.67, p < 0.001), followed by pertuzumab (HR: 0.72, 95% Cl: 0.55–0.89, p = 0.001). Trastuzumab benefited the least, with no difference statistical significance (HR: 0.87, 95% Cl: 0.31–1.44, p = 0.594). In terms of treatment regimen, first-line treatment (HR: 0.67, 95% Cl: 0.52–0.82, p < 0.001) had a greater benefit than non-first-line treatment (HR: 0.82, 95% Cl: 0.71–0.94, p = 0.004). The main adverse events (AEs) observed were diarrhea and the main cardiotoxicity observed was decreased ejection fraction.Conclusions Additional anti-HER2-targting drugs may improve long-term prognosis in HER2-positive advanced breast cancers. Moreover, the AEs were safe and tolerable. Besides, lapatinib had the best benefit, and pertuzumab followed by, trastuzumab had the least benefit in terms of drug selection. From the aspect of treatment, it recommended significantly to use anti-HER2-targeting drugs in first-line therapy based on our research in HER2-positive advanced breast cancers.

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“…In addition to the high proportion of cancers with PI3K pathway mutations, PI3K activity has been implicated in mediating signals from other driver mutations including RAS (9)(10)(11) and RTKs, such as the human epidermal growth factor receptor, HER2 (12,13). PI3K activation has also been suggested as a mechanism of tumor escape from HER2targeted therapies (14)(15)(16), and combination inhibition of PI3K with HER2 has improved efficacy in preclinical models leading to clinical trials of the combination (17). The first clinical trial to report on this combination used buparlisib, a pan-PI3K inhibitor, with trastuzumab, a HER2 inhibitor, and was only able to resensitize trastuzumab-resistant breast cancers in 10% of cases (18).…”

Section: Pi3k As An Oncogenementioning

confidence: 99%

Treating cancer with phosphatidylinositol-3-kinase inhibitors: increasing efficacy and overcoming resistance

Paddock¹,

Field²,

Cantley³

2019

Journal of Lipid Research

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Cell growth and proliferation in higher organisms such as humans normally depends on instructive signals provided by growth factors. These signals are transduced Abstract The discovery of the phosphatidylinositol-3-kinase (PI3K) pathway was a major advance in understanding growth factor signaling. The high frequency of PI3K pathway mutations in many cancers has encouraged a new field targeting cancer driver mutations. Although there have been many successes, targeting PI3K itself has proven challenging, in part because of its multiple isoforms with distinct roles. Despite promising preclinical results, development of PI3K inhibitors as pharmacologic anticancer agents has been limited by modest single-agent efficacy and significant adverse effects. If we could overcome these limitations, PI3K inhibitors would be a powerful cancer-fighting tool. Data from phase III clinical trials yields insight into some of the problems with PI3K inhibitors. Recent advances have shed light on the mechanisms of tumor resistance to PI3K inhibitors via feedback pathways that cause elevated insulin levels that then activate the same PI3K pathways that are the targets of inhibition. Improving our understanding of the complex regulatory feedback pathways that activate in response to PI3K inhibition will reveal ways to increase the efficacy of PI3K inhibitors and reduce adverse effects, increasing the usefulness of this class as a treatment option for multiple cancer types.-Paddock, M. N., S. J. Field, and L. C. Cantley. Treating cancer with phosphatidylinositol-3-kinase inhibitors: increasing efficacy and overcoming resistance. J. Lipid Res. 2019. 60: 747-752.

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First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2–Positive and Hormone Receptor–Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial

Abstract: PERTAIN met its primary PFS end point. Pertuzumab plus trastuzumab and an AI is effective for the treatment of HER2-positive MBC/LABC. The safety profile was consistent with previous trials of pertuzumab plus trastuzumab.

Cited by 181 publications

References 21 publications

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Review A meta-analysis of the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancers

Treating cancer with phosphatidylinositol-3-kinase inhibitors: increasing efficacy and overcoming resistance

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