Alpelisib (ALP) + fulvestrant (FUL) for patients with hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC): Management and time course of key adverse events of special interest (AESIs) in SOLAR-1

Rugo, Hope S.; André, Fabrice; Yamashita, Takashi; Cerda, Humberto; Toledano, I.; Stemmer, Salomon M.; Jurado, Josefina Cruz; Juric, Dejan; Mayer, Ingrid A.; Ciruelos, Eva; Iwata, Hiroji; Conte, Pier Franco; Campone, Mario; Wilke, Celine; Mills, David; Lorenzo, Innocenzo Di; Miller, Michelle C.; Loibl, Sibylle

doi:10.1093/annonc/mdz242.019

Cited by 6 publications

(10 citation statements)

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“…Therefore, in the SOLAR-1 trial evaluating alpelisib (BYL719), an α-specific PI3K inhibitor combined with fulvestrant, the most common grade 3 or 4 adverse events of special interest were hyperglycemia (high blood sugar), rash and diarrhea. 58 This toxic profile is similar to other PI3K inhibitors.…”

Section: Introductionsupporting

confidence: 58%

Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer

et al. 2020

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Recently many therapeutic classes have emerged in advanced hormone receptor-positive breast cancer, which is the leading cause of cancer death in women. In absence of visceral crisis, treatment relies on endocrine therapy combined with cyclin dependent kinase 4 and 6 inhibitor. Many mechanisms lead to resistance to endocrine therapy, including the activation of intracellular signaling pathways critical for cell survival. Approximately 70% of breast tumors harbor an alteration in the phosphoinositide 3 kinase (PI3K)/Akt pathway, leading to its hyper activation. This pathway is involved in the regulation of growth, proliferation and cell survival as well as in angiogenesis and is consequently a major target in the oncogenesis. An aberrant PIK3CA mutation is a common phenomenon in breast cancer and found in approximately 40% of patients with advanced hormone receptor-positive breast cancer. For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes).

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Section: Introductionsupporting

confidence: 58%

Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer

et al. 2020

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“…Редукция дозы потребовалась 62,1% пациенток [6]. При этом снижение дозы или отмена препарата влияли на эффективность лечения [9]. С учетом механизма действия алпелисиба наиболее частыми нежелательными эффектами, приводящими к отмене препарата или редукции дозы, являются гипергликемия, сыпь и диарея.…”

Section: рис 2 кт (февраль 2021 г): полная редукция опухолевых очаговunclassified

“…Результаты исследований SOLAR-1 и BYLieve продемонстрировали не только эффективность препарата, но и новые, свойственные этой терапии виды токсичности. На сегодняшний день разработаны рекомендации по профилактике и лечению наиболее частых нежелательных явлений, позволяющие использовать препарат максимально безопасно [9]. Результаты исследования расценены как стабилизация на фоне проводимого лечения, рекомендовано продолжение терапии с оценкой эффекта через три месяца.…”

Section: Introductionunclassified

The Use of Alpelisib in Metastatic Estrogen-Receptor-Positive HER2/Neu-Negative Breast Cancer

Yukalchuk¹,

Ponomarenko²,

Yukalchuk³

et al. 2022

EPh

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The clinical case presented in the article demonstrates the effectiveness of orange in combination with fulvestrant in metastatic estrogen receptor-positive HER2/neu-negative breast cancer with a mutation in the PIK3CA gene. The resistance of hormone therapy requires the search for new therapeutic options. The results of the SOLAR-1 and BYLieve studies have shown not only the effectiveness of alpelisib, but also new types of toxicity characteristic of this therapy. At the moment, recommendations have been developed for the prevention and treatment of the most frequent adverse events, allowing the drug to be used as safely as possible. With the introduction of alpelisib, the possibilities of non-chemotherapeutic treatment options for prognostically unfavorable patients have not only expanded, but there has also been a trend towards the use of personalized medicine and targeted therapy.

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“…PI3Ki-associated toxicities will generally be reversible if managed adequately. 79 Some of the commonly observed toxicities associated with PI3Ki treatment have included hyperglycemia, rash, and diarrhea. [65][66][67][68] Successful implementation of management strategies and monitoring schedules is vital for maximizing the clinical benefit to patients.…”

Section: Ae Management: Practical Considerationsmentioning

confidence: 99%

“…To reduce the frequency and severity of rash, prophylactic antihistamine treatment has been recommended, starting on the first day of PI3Ki treatment. 79 Guidance for rash management includes the use of topical steroids for lower grade events. Low-dose systemic corticosteroid treatment can be considered for managing grade 2 rash.…”

Section: Ae Management: Practical Considerationsmentioning

confidence: 99%

Targeting PIK3CA Alterations in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2–Negative Advanced Breast Cancer: New Therapeutic Approaches and Practical Considerations

Schwartzberg

Vidal

2020

Clinical Breast Cancer

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The phosphatidylinositol-3-kinase (PI3K) pathway is frequently dysregulated in human breast cancer. Approximately 30% of all patients with breast cancer will carry mutations of the PIK3CA gene, which encodes the PI3K catalytic subunit isoform p110a. Mutations in PIK3CA have been associated with resistance to endocrine therapy, HER2-directed therapy, and cytotoxic therapy. Early trials of pan-PI3K inhibitors showed little treatment benefit as monotherapy owing to disease resistance arising through enhanced estrogen receptor pathway signaling. Combining PI3K inhibition with endocrine therapy can help overcome resistance. Clinical trials of pan-PI3K inhibitors combined with endocrine therapy demonstrated modest clinical benefits but challenging toxicity profiles, facilitating the development of more selective PI3K-targeting agents. More recent trials of isoform-specific PI3K inhibitors in patients with PIK3CA mutations have shown promising clinical efficacy with a predictable, manageable safety profile. In the present review, we discuss the clinical relevance of mutations of PIK3CA and their potential use as a biomarker to guide treatment choices in patients with HR þ HER2 À advanced breast cancer.

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Alpelisib (ALP) + fulvestrant (FUL) for patients with hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC): Management and time course of key adverse events of special interest (AESIs) in SOLAR-1

Cited by 6 publications

References 0 publications

Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer

Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer

The Use of Alpelisib in Metastatic Estrogen-Receptor-Positive HER2/Neu-Negative Breast Cancer

Targeting PIK3CA Alterations in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2–Negative Advanced Breast Cancer: New Therapeutic Approaches and Practical Considerations

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