Alpesib

Alpesib is indicated in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CAmutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models.

In breast cancer cell lines, Alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, Alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer.

PI3K inhibition by Alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of Alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines.

Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models.

In breast cancer cell lines, Alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, Alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer.

PI3K inhibition by Alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of Alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines.

Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models.

In breast cancer cell lines, Alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, Alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer.

PI3K inhibition by Alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of Alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines.

Alpelisib is contraindicated in patients with severe hypersensitivity to it or any of its components.

• Severe allergic reactions
• Diarrhea
• Severe skin reactions
• Lung problems (pneumonitis)
• High blood sugar levels (hyperglycemia)

Pregnancy: Based on animal data and mechanism of action, Alpelisib can cause fetal harm when administered to a pregnant woman.

Lactation: There is no data on the presence of Alpelisib in human milk, its effects on milk production, or the breastfed child. Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with Alpelisib and for 1 week after the last dose.

Infertility: Based on findings from animal studies, Alpelisib may impair fertility in males and females of reproductive potential.

Severe Hypersensitivity: Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue Alpesib in the event of severe hypersensitivity.

Severe Cutaneous Reactions: Severe cutaneous reactions, including Stevens-Johnson Syndrome (SJS) and Erythema Multiforme (EM) were reported in patients treated with Alpesib. Advise patients of the signs and symptoms of severe cutaneous reactions (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions or progressive skin rash).

Hyperglycemia: Before initiating treatment with Alpesib, test FPG, HbA1c, and optimize blood glucose. After initiating treatment with Alpesib, monitor blood glucose and/or FPG at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinically indicated. Based on the severity of the hyperglycemia, Alpesib may require dose interruption, reduction, or discontinuation.

Pneumonitis: Permanently discontinue Alpesib in all patients with confirmed pneumonitis. Advise patients to immediately report new or worsening respiratory symptoms.

Diarrhea: Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking Alpesib.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, Alpesib can cause fetal harm when administered to a pregnant woman.

No clinically significant differences in the pharmacokinetics of Alpesib were predicted based on age (21 to 87 years), sex, race/ethnicity (Japanese or Caucasian), body weight (37 to 181 kg), mild to moderate renal impairment (CrCl 30 to < 90 mL/min based on the Cockcroft-Gault formula), or mild to severe hepatic impairment (Child-Pugh Class A, B, and C). The effect of severe renal impairment (CrCl < 30 mL/min) on the pharmacokinetics of Alpesib is unknown.

Pediatric Use: The safety and efficacy of Alpesib in pediatric patients have not been established

Geriatric Use: No overall differences in effectiveness of Alpesib were observed between patients ≥65 years of age compared to younger patients. There are an insufficient number of patients ≥75 years of age to assess whether there are differences in safety or effectiveness.

Renal Impairment: The effect of severe renal impairment (CLcr <30 mL/min) on Alpesib pharmacokinetics is unknown. No dose adjustment is recommended for patients with mild to moderate renal impairment (CLcr 30 to <90 mL/min).

Cytotoxic Chemotherapy

Cytotoxic Chemotherapy