The FDA has recently approved two significant therapies for breast cancer, offering new hope for patients at different stages of the disease. Ribociclib (Kisqali) has been approved for adjuvant treatment of early-stage hormone receptor-positive, HER2-negative breast cancer, while inavolisib (Itovebi) has been approved for advanced or metastatic cases with specific genetic mutations. These approvals mark pivotal advancements in breast cancer care, providing clinicians with more targeted and effective tools to combat this prevalent disease. These approvals highlight the importance of personalized medicine and biomarker testing in tailoring treatment strategies for improved patient outcomes.
Kisqali Approved for Early-Stage Breast Cancer
Novartis' Kisqali, in combination with an aromatase inhibitor (AI), has received FDA approval for the adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) stage II and III early breast cancer (EBC) at high risk of recurrence. This approval, announced on September 17, 2024, is based on the Phase III NATALEE trial, which demonstrated a clinically meaningful 25.1% reduction in the risk of disease recurrence (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006). The invasive disease-free survival (iDFS) benefit was consistently observed across all patient subgroups, including those with node-negative (N0) disease.
Dr. Dennis J. Slamon, Director of Clinical/Translational Research at UCLA Jonsson Comprehensive Cancer Center, emphasized the significance of this approval, stating, "The FDA approval of Kisqali for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care. Today’s approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning."
In the NATALEE trial, Kisqali was administered orally at a dose of 400 mg daily for three weeks, followed by one week off treatment, in combination with an AI for three years. The safety profile of Kisqali at the 400 mg dose was well-tolerated, with discontinuations mainly driven by asymptomatic laboratory findings. Common adverse events included neutropenia, liver-related AEs, QT interval prolongation, and interstitial lung disease/pneumonitis.
Itovebi Approved for Advanced Breast Cancer
On October 10, 2024, the FDA approved Genentech's Itovebi (inavolisib), in combination with palbociclib and fulvestrant, for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer. This approval is based on the Phase III INAVO120 study, which showed that the Itovebi-based regimen reduced the risk of disease worsening or death by 57% compared with palbociclib and fulvestrant alone (HR=0.43, 95% CI: 0.32-0.59, p<0.0001).
The INAVO120 study involved 325 patients whose disease progressed during or within 12 months of completing adjuvant endocrine therapy. The median progression-free survival (PFS) was 15.0 months in the inavolisib arm compared to 7.3 months in the placebo arm. The objective response rate (ORR) was 58% in the inavolisib arm versus 25% in the placebo arm. Common adverse reactions included decreased neutrophils, increased fasting glucose, decreased hemoglobin, and diarrhea.
Dr. Komal Jhaveri, section head for the endocrine therapy research portfolio at Memorial Sloan Kettering Cancer Center, noted, "The PI3K pathway plays a pivotal role in disease progression and has been challenging to target. The Itovebi-based regimen more than doubled progression-free survival and maintained a manageable safety and tolerability profile, adding a new standard in how PIK3CA-mutated breast cancers are treated."
Implications for Breast Cancer Treatment
These FDA approvals represent significant advancements in the treatment of breast cancer. The expanded use of Kisqali offers a new adjuvant treatment option for a broader population of patients with early-stage disease, while the approval of Itovebi provides a targeted therapy for advanced cases with PIK3CA mutations. These developments underscore the importance of personalized medicine and biomarker testing in tailoring treatment strategies for improved patient outcomes.
