Dr Rugo on the FDA Approval of Inavolisib Plus Palbociclib and Fulvestrant in PIK3CA-mutated HR+/HER2– Breast Cancer

Hope S. Rugo, MD, professor, medicine, Department of Medicine (Hematology/Oncology), Winterhof Family Distinguished Professor of Breast Oncology, director, Breast Oncology and Clinical Trials Education, medical director, Cancer Infusion Services, UCSF Helen Diller Family Comprehensive Cancer Center, discusses the significance of the FDA approval of inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant (Faslodex) in adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer.

On October 10, 2024, the FDA approved inavolisib in combination with palbociclib and fulvestrant for the treatment of patients within this population. The regulatory decision was supported by data from the phase 3 INAVO120 trial (NCT04191499) which demonstrated that patients treated with inavolisib plus palbociclib and fulvestrant achieved a median progression-free survival (PFS) of 15.0 months (95% CI, 11.3-20.5) compared with 7.3 months (95% CI, 5.6-9.3) for those treated with placebo plus palbociclib and fulvestrant (HR, 0.43; 95% CI, 0.32-0.59; P < .0001).

Rugo explains that this approval marks an important milestone in the therapeutic landscape of endocrine-resistant disease, particularly in patients whose disease has relapsed following adjuvant endocrine therapy with aromatase inhibitors or tamoxifen.

Inavolisib targets the PI3K pathway, which plays a critical role in resistance mechanisms in PIK3CA-mutated breast cancers, she explains. The combination with CDK4/6 inhibitors and endocrine therapy offers a new approach to improve outcomes in patients whose disease did not respond well to first-line treatment, she emphasizes.

Rugo highlights that INAVO120, which supported this regulatory approval, included patients with at high-risk of early progression. These patients were randomized to receive either the standard doublet of palbociclib and fulvestrant or the triplet regimen of inavolisib, palbociclib, and fulvestrant.

The trial demonstrated a significant improvement in PFS for the triplet arm, Rugo explains, adding that the 0.43 hazard ratio underscores the efficacy of this approach.

Importantly, the trial also showed that inavolisib was well tolerated, with manageable toxicity, Rugo continues. Patient selection played a key role in minimizing adverse effects, as the trial excluded individuals with diabetes or glucose intolerance, she explains. This approval provides an exciting new treatment option for patients with PIK3CA-mutated breast cancer, offering a significant advance in managing this challenging population, Rugo concludes.