Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the U.S. Food and Drug Administration (FDA) has approved Itovebi™ (inavolisib) for use in combination with palbociclib (Ibrance®) and fulvestrant to treat adults with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer. This approval applies to patients who have experienced recurrence following adjuvant endocrine therapy and whose PIK3CA mutation has been confirmed by an FDA-approved test. Approximately 40% of HR-positive metastatic breast cancers carry the PIK3CA mutation.
Dr. Komal Jhaveri, a leading investigator of the INAVO120 study and an expert at Memorial Sloan Kettering Cancer Center, highlighted the significance of the approval, noting that targeting the PI3K pathway has been challenging despite its key role in disease progression. “The Itovebi-based treatment more than doubled progression-free survival while maintaining a manageable safety profile, setting a new standard for treating PIK3CA-mutated breast cancers,” Dr. Jhaveri said.
Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, emphasized the importance of the approval in addressing a significant unmet need. “PIK3CA mutations are common in this patient population, but treatment options have been limited. This new first-line option represents a crucial advancement,” he stated.
The approval is based on findings from the Phase III INAVO120 study, which demonstrated that the Itovebi-based regimen significantly improved progression-free survival compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months), reducing the risk of disease progression or death by 57% (hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001). Though the overall survival data was not mature at the time of analysis, there was a promising trend toward improved survival (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338), and further follow-up is ongoing.
Jean Sachs, CEO of Living Beyond Breast Cancer, expressed optimism about the impact of this approval on patients with advanced breast cancer. “This is a major step forward, and it’s crucial that all patients undergo early and comprehensive biomarker testing to better understand their treatment options,” she said.
The FDA granted Priority Review and Breakthrough Therapy Designation to the Itovebi-based regimen in May 2024 due to the INAVO120 study results. Roche is also pursuing regulatory approvals with other global health authorities, including the European Medicines Agency. Itovebi is expected to be available in the U.S. soon. Comprehensive biomarker testing, such as Foundation Medicine’s FoundationOne®Liquid CDx, can help identify patients with HR-positive, HER2-negative breast cancer with PIK3CA mutations.
Roche is further investigating Itovebi across multiple Phase III clinical trials (INAVO120, INAVO121, and INAVO122) in PIK3CA-mutated, locally advanced or metastatic breast cancer, with ongoing efforts to expand its clinical development program in oncology to meet unmet patient needs.
