New Treatment for Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer Approved

Introduction

On November 16, 2023, the U.S. Food and Drug Administration approved capivasertib (Truqap) for use in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer in patients with one or more PIK3CA/AKT1/PTEN alterations. The approval followed disease progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy. The FoundationOneCDx assay received approval as a companion diagnostic device to identify patients with breast cancer for treatment with capivasertib with fulvestrant.

Improvement in Progression-Free Survival

A significant improvement in progression-free survival was observed in the capivasertib group in the overall population and among patients with PIK3CA/AKT1/PTEN alteration. The median progression-free survival was 7.3 months (95% CI = 5.5–9.0 months) in the capivasertib group vs 3.1 months (95% CI = 2.0–3.7 months) in the control group (hazard ratio = 0.50, 95% CI = 0.38–0.65, P < .0001).

Recommended Dosage

The recommended capivasertib dose is 400 mg twice daily for 4 days followed by 3 off days until disease progression or unacceptable toxicity. Dosage modifications, including dose reduction, for adverse reactions are provided in the product labeling.

Avoid Concomitant Use with Strong CYP3A Inhibitors and Inducers

Concomitant use with strong CYP3A inhibitors (eg, clarithromycin, erythromycin, fluconazole) and strong and moderate CYP3A inducers (eg, glucocorticoids, rifampin, phenobarbital) should be avoided.

Adverse Events and Safety

Safety data for capivasertib are from 155 patients in the capivasertib group and 133 patients in the control group in CAPItello-291 who had PIK3CA/AKT1/PTEN alteration. The most common adverse events of any grade in the capivasertib group occurring at an incidence at least 3% higher than in the control group were:

Diarrhea (77% vs 19%)
Cutaneous adverse reactions (56% vs 16%)
Fatigue (38% vs 27%)
Nausea (35% vs 14%)
Stomatitis (25% vs 5%)

The most common grade 3 or 4 adverse events in the capivasertib group included cutaneous adverse events (15%), diarrhea (12%), and renal injury (2.6%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (11%) and increased random glucose (9%).

Serious adverse events occurred in 18% of patients in the capivasertib group, most commonly cutaneous adverse events (3.9%), diarrhea (2.6%), and pneumonia (2.6%). Adverse events led to the discontinuation of capivasertib in 10% of patients, most commonly cutaneous adverse events (6%). Fatal adverse events occurred in 1.3%, including sepsis (0.6%) and acute myocardial infarction (0.6%).

Warnings/Precautions

Capivasertib has warnings/precautions for hyperglycemia, diarrhea, cutaneous adverse reactions, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving capivasertib.

Conclusion

The approval of capivasertib for the treatment of hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer in patients with one or more PIK3CA/AKT1/PTEN alterations is a significant advancement in breast cancer treatment. Clinicians and patients must be aware of the potential adverse events and appropriate intercourse with strong CYP3A inhibitors and inducers. The approval of the FoundationOneCDx assay as a companion diagnostic will help identify patients who could benefit most from this new treatment modality.

Originally Post From https://ascopost.com/issues/july-10-2024/capivasertib-with-fulvestrant-for-previously-treated-advanced-hormone-receptor-positive-her2-negative-breast-cancer/

Capivasertib combined with Fulvestrant shows promise for advanced Hormone Receptor-positive patients