SABCS
by Wayne Kuznar,
Contributing Writer
December 10, 2023
SAN ANTONIO — The addition of inavolisib to palbociclib (Ibrance) plus fulvestrant (Faslodex) boosted progression-free survival (PFS) in patients with recurrent PIK3CA-mutated HR-positive, HER2-negative advanced breast cancer, according to the INAVO120 trial.
In patients who recurred within 12 months of adjuvant endocrine therapy, treatment with the investigational selective PI3Kα inhibitor demonstrated more than a doubling of median PFS from 7.3 to 15 months (stratified HR 0.43, P<0.0001), reported Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York City.
There also was a trend toward improved overall survival (OS) at the first interim analysis (median follow-up of 21.3 months) with inavolisib compared with placebo as add-on therapy, she said at a San Antonio Breast Cancer Symposium (SABCS) press briefing.
Jhaveri stated that the triplet therapy “may represent a new standard of care for patients with PIK3CA-mutated HR-positive, HER2-negative advanced breast cancer. What we have learned so far is that we have not been able to combine alpelisib with a CDK4/6 inhibitor, due to the challenges with the safety profile. This is the very first time we’ve been able to use a triplet combination of inavolisib with a CDK4/6 inhibitor and endocrine therapy, guided by preclinical data showing synergistic activity.”
“What is reassuring is not only the favorable impact on efficacy, but we’re seeing low discontinuation rates with such a triplet regimen,” she noted. The discontinuation rate was 6.8% with inavolisib treatment group versus 0.6% for palbociclib and fulvestrant alone, according to a Genentech/Roche press release.
Inavolisib is an oral highly potent and selective inhibitor of the PI3K catalytic subunit α isoform protein that also promotes the degradation of p110α, which may improve the therapeutic window. Currently available α isoform PI3K inhibitors have faced challenges with safety and tolerability, she said.
Palbociclib received FDA approval in 2015 in combination with letrozole for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The agent’s indication was expanded in 2019 as a treatment for men with with HR+, HER2- metastatic breast cancer.
Trial Details
INAVO120 is a phase III, randomized, double-blind placebo-controlled study that assessed inavolisib combined with palbociclib plus fulvestrant or placebo and the latter two agents (control arm) in patients with PIK3CA-mutated HR-positive HER2-negative advanced breast cancer.
Eligible patients had measurable disease and had progression during or within 12 months of completion of adjuvant endocrine therapy. No prior therapy for advanced breast cancer was allowed. Eligibility criteria included a fasting glucose <126 mg/dL and the hemoglobin A1c <6%.
A total of 325 patients were randomized 1:1 to the triplet regimen of inavolisib (9 mg orally daily) with standard of care doses of palbociclib with fulvestrant or placebo with standard of care doses of palbociclib and fulvestrant until progression or toxicity.