NEJM publishes landmark phase III results for Roche's Itovebi, doubling progression-free survival in HR-positive advanced breast cancer

Roche has reported the results of a detailed analysis from the phase III INAVO120 study, which evaluated the efficacy of Itovebi (inavolisib) in combination with palbociclib (Ibrance) and fulvestrant. The findings were published in the New England Journal of Medicine. Itovebi's combination therapy was recently approved by the U.S. FDA for treating adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer, following recurrence after adjuvant endocrine therapy. This approval marks a significant step in the treatment of this specific breast cancer subtype.

The INAVO120 study demonstrated that the Itovebi-based regimen significantly reduced the risk of disease progression or death by 57% compared to the use of palbociclib and fulvestrant alone. Specifically, the progression-free survival (PFS) was extended to 15 months in the Itovebi group, in contrast to 7.3 months in the control group. The hazard ratio (HR) was 0.43, with a 95% confidence interval (CI) of 0.32-0.59, and the result was statistically significant (p<0.001). The PFS benefit was observed consistently across all subgroups, including those with disease spread to multiple challenging locations such as the liver and lungs.

The study's principal investigator, Dr. Komal Jhaveri of Memorial Sloan Kettering Cancer Center, emphasized the significance of these findings, noting the potential of Itovebi to set a new first-line standard of care for patients with PIK3CA-mutated metastatic breast cancer. Despite the overall survival (OS) data being immature, there was a clear positive trend, and follow-up for OS will continue in future analyses.

Dr. Levi Garraway, Roche’s Chief Medical Officer, highlighted the transformative potential of the Itovebi-based regimen, stressing Roche's commitment to targeting specific disease pathways and improving outcomes for breast cancer patients. The importance of comprehensive testing for mutations like PIK3CA at diagnosis was also emphasized to identify candidates for targeted therapies such as Itovebi.

PIK3CA mutations are prevalent in approximately 40% of HR-positive metastatic breast cancers and are linked with poor prognosis. Historically, PI3K targeted therapy's use in early treatment settings has been limited, and thus, PIK3CA mutation testing is not routine at diagnosis. Early biomarker testing, such as through Foundation Medicine’s FoundationOne Liquid CDx, is crucial for identifying patients who could benefit from targeted treatments.

Itovebi is currently under investigation in additional clinical trials. The INAVO121 study compares Itovebi plus fulvestrant with alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 inhibitor and endocrine combination therapy. The INAVO122 study evaluates Itovebi in combination with pertuzumab and trastuzumab for subcutaneous injection versus the same combination with optional physician's choice of endocrine therapy in HER2-positive disease.

HR-positive breast cancer, characterized by hormone receptor-positive tumor cells, is the most common breast cancer subtype, representing about 70% of cases. Tumors in HR-positive breast cancer have receptors for hormones like estrogen and progesterone, which can promote tumor growth. Patients with HR-positive metastatic breast cancer face ongoing risks of disease progression and treatment-related side effects, necessitating new treatment options.

Roche has been at the forefront of breast cancer research for over three decades, contributing significantly to advancements in human epidermal growth factor 2-positive and triple-negative breast cancers. With ongoing research, Roche aims to discover new biomarkers and treatment approaches for various breast cancer subtypes, including estrogen receptor-positive breast cancer.

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