Genentech, a member of the Roche Group, has announced positive topline results from the overall survival (OS) analysis of the Phase III INAVO120 study. The study investigated Itovebi (inavolisib) in combination with palbociclib and fulvestrant for patients with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The results, published in the New England Journal of Medicine, indicate a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen compared to palbociclib and fulvestrant alone. These findings suggest a potential new first-line treatment option for this patient population with a poor prognosis.
INAVO120 Study Details and Results
The INAVO120 study (NCT04191499) is a Phase III, randomized, double-blind, placebo-controlled trial involving 325 patients. It evaluated the efficacy and safety of Itovebi in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer whose disease progressed during or within 12 months of completing adjuvant endocrine therapy and who had not received prior systemic therapy for metastatic disease.
The primary endpoint of the study was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate, and clinical benefit rate. The previously reported primary analysis demonstrated that the Itovebi-based regimen reduced the risk of disease worsening or death by 57% compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001). The OS data, initially immature, now show a statistically significant benefit (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338).
Clinical Significance and Expert Commentary
Dr. Komal Jhaveri, section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center, highlighted the significance of the findings: "With a doubling of progression-free survival and consistent benefits in people whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients. I’m confident this Itovebi-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis."
The Role of PIK3CA Mutations in Breast Cancer
The PIK3CA mutation is present in approximately 40% of HR-positive metastatic breast cancers and is associated with a poorer prognosis. Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development, emphasized the importance of comprehensive testing for mutations like PIK3CA at the time of diagnosis to identify patients who may benefit from targeted therapy, such as Itovebi.
Ongoing Research and Future Directions
Itovebi is currently being investigated in two additional company-sponsored Phase III clinical studies: INAVO121 (NCT05646862) and INAVO122 (NCT05894239), in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations. These studies aim to further explore the potential of Itovebi in different settings and combinations to address unmet needs in breast cancer treatment.
Safety Profile
No new safety signals were observed in the OS analysis compared to the previous analysis. Common side effects associated with Itovebi include high blood sugar levels, mouth sores, and diarrhea. Healthcare providers are advised to monitor patients for these side effects and manage them appropriately.
