Inavolisib Plus Palbociclib and Fulvestrant Improves PFS in PIK3CA-Mutated HR+ Breast Cancer

Levi Garraway, MD, PhD

The addition of inavolisib to palbociclib (Ibrance) and fulvestrant (Faslodex) improved progression-free survival (PFS) vs palbociclib and fulvestrant alone in select patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer, meeting the primary end point of the phase 3 INAVO120 trial (NCT04191499).¹

Although overall survival (OS) data were immature, a trend favoring the inavolisib regimen was reported.

The combination was also found to have favorable tolerability with adverse effects (AEs) mirroring what has previously been reported with each agent. No new safety signals were observed.

“These pivotal study results for this inavolisib combination could represent a transformative medical advance for people with PIK3CA-mutated hormone receptor–positive breast cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, stated in a press release. “We look forward to expanding our portfolio of breast cancer medicines into the hormone receptor–positive space and bringing this potentially best-in-class new treatment option to patients as quickly as possible.”

The double-blind, placebo-controlled, randomized phase 3 trial enrolled patients with hormone receptor–positive, HER2-negative breast cancer who had metastatic or locally advanced disease that was not amenable to curative treatment.² Patients must have progressed during or within 1 year of adjuvant treatment with endocrine therapy in the form of an aromatase inhibitor or tamoxifen.

If pre- or perimenopausal, patients must have received luteinizing hormone-releasing hormone receptor therapy for at least 2 weeks before day 1 of the first cycle of study treatment. Other inclusion criteria were measurable disease by RECIST v1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of longer than 6 months, and acceptable hematologic and organ function.

Patients with metaplastic breast cancer, any history of leptomeningeal disease or carcinomatous meningitis, and known and untreated or active central nervous system metastases were excluded. Patients could not have prior receipt of systemic treatment for metastatic breast cancer, fulvestrant, or any selective estrogen-receptor degrader, or any PI3K, AKT, or mTOR inhibitor.

Other exclusion criteria included having received anticancer therapy within 2 weeks before study entry, investigational agents within 4 weeks prior to randomization, and previous radiation to at least 25% of the bone marrow.

A total of 325 patients were randomly assigned to receive inavolisib on days 1 to 28 of each 28-day cycle or placebo plus oral palbociclib on days 1 to 21 of each 28-day cycle and intramuscular fulvestrant about every 4 weeks.^1,2

In addition to investigator-assessed PFS serving as the primary end point of the trial, secondary end points included OS, objective response rate, and clinical benefit rate.¹

Findings will be discussed with health authorities and shared at an upcoming medical meeting, according to Genentech.

References

1. Genentech announces positive phase III results for inavolisib combination in people with advanced hormone receptor-positive HER2-negative breast cancer with a PIK3CA mutation. News release. Genentech. December 4, 2023. Accessed December 7, 2023. https://www.gene.com/media/press-releases/15011/2023-12-04/genentech-announces-positive-phase-iii-r
2. A study evaluating the efficacy and safety of inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, Her2-negative, locally advanced or metastatic breast cancer (INAVO120). ClinicalTrials.gov. Updated November 18, 2023. Accessed December 7, 2023. https://clinicaltrials.gov/study/NCT04191499