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Inavolisib in Combination With Palbociclib and Fulvestrant Meets Secondary End Point in the INAVO120 Trial
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Key Takeaways
- Inavolisib, a selective PIK3CA inhibitor, targets the PI3K alpha isoform, reducing treatment toxicity in HR+, HER2– breast cancer.
- The INAVO120 trial showed inavolisib significantly improved progression-free survival to 15 months compared to 7.3 months with placebo.
The overall survival data were immature at the primary analysis of the study.
Inavolisib (Itovebi; Roche) in combination with palbociclib (Ibrance; Pfizer) and fulvestrant (Faslodex; AstraZeneca) met its secondary end point of overall survival (OS) in the INAVO120 trial (NCT04191499). The findings build upon data from the primary analysis of the study and reinforce the potential benefits of an inavolisib-based regimen.1
Depiction of hormones and hormone receptors | Image Credit: © MAY - stock.adobe.com
Hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2–) breast cancer (BC) accounts for 70% of all diagnoses, making it the most prevalent BC subtype. It is associated with poorer prognoses and outcomes with high risk of disease reoccurrence, disease progression, and treatment adverse effects. In HR+, HER2– BC, normal functioning of the PI3K signaling pathway is interrupted, leading to activation of PIK3CA mutations. Research has identified that these mutations may drive intrinsic resistance to standard of care endocrine therapy (ET) in combination with CDK4/6 inhibitors.2,3
Inavolisib is a highly potent, selective inhibitor of PIK3CA designed to mitigate the overall burden and toxicity associated with treatment. Compared with other PI3K inhibitors, inavolisib targets and facilitates the degradation of the PI3K alpha isoform. In the phase 3, double-blind, randomized INAVO120 trial, treatment with first-line oral inavolisib at a dose of 9 mg once daily plus palbociclib and fulvestrant yielded significantly longer PFS.2,3
The trial aimed to determine the safety and efficacy of inavolisib in combination with palbociclib and fulvestrant vs placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutated, HR+, HER2–, locally advanced or metastatic BC who experienced disease progression during treatment or within 12 months of completing adjuvant ET and who have not received prior systemic therapy for metastatic disease. The primary end point was PFS, with secondary end points including OS, objective response rate (ORR), and clinical benefit rate.2,3
The researchers evaluated 325 patients who were randomly assigned to the inavolisib group (n=161) or the placebo group (n=164). In the primary analysis of the trial data, the PFS of patients in the inavolisib arm was 15 months (95% confidence interval [CI], 11.3 to 20.5) compared with 7.3 months in the placebo arm (95% CI, 5.6 to 9.3). There were reported ORRs of 58.4% and 25% in the inavolisib group and the placebo group, respectively.3
The OS data were immature at the time of the primary analysis, but there was a positive trend (stratified HR=0.64, 95% CI: 0.43-0.97, P=0.0338 [boundary of 0.0098]). In a January 2025 update on the data, the company reported the trial met its OS end point.2,3
"The INAVO120 [OS] results show that the [inavolisib]-based regimen not only delayed disease progression, but also helped people with advanced HR-positive, PIK3CA-mutated breast cancer live longer,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, in a press release. “The [inavolisib]-based regimen has the potential to become the new standard of care for these patients.”2
