Officials with the FDA have approved inavolisib (Itovebi, Genentech, Inc.) with palbociclib (Ibrance) and fulvestrant (Faslodex) for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth-factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.1
Researchers evaluated the treatment’s efficacy in the INAVO120 (NCT04191499) trial, which randomly assigned 325 patients with endocrine-resistant, PIK3CA-mutated HR-positive, HER2-negative locally advanced or metastatic breast cancer whose disease had progressed within a year of completing adjuvant endocrine therapy and who had not received prior systemic therapy for locally advanced or metastatic disease. The researchers defined primary endocrine resistance as relapse while on the first 2 years of adjuvant endocrine therapy (ET) and secondary endocrine resistance was defined as relapse while on adjuvant ET after at least 2 years, or relapse within 12 months of completing adjuvant ET.
Patients were randomly assigned 1:1 to either inavolisib 9 mg or placebo orally once daily, with palbociclib 125 mg orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a cycle of 28 days, and fulvestrant 500 mg administered intramuscularly on cycle 1, days 1 and 15, and then on day 1 of every 28-day cycle. Patients received treatment until disease progression or unacceptable toxicity.
The major efficacy outcome measure was investigator-assessed progression-free survival (PFS) per RECIST version 1.1. Additional efficacy outcome measures included overall survival (OS), investigator-assessed objective response rate (ORR), and duration of response (DOR).
Median progression-free survival was 15 months in the inavolisib + palbociclib + fulvestrant arm and 7.3 months in the placebo + palbociclib + fulvestrant arm. Objective response rate was 58% (95% CI: 50-66) in the inavolisib + palbociclib + fulvestrant arm and 25% (95% CI: 19-32) in the placebo + palbociclib + fulvestrant arm. Median duration of response was 18.4 months (95% CI: 10.4-22.2) and 9.6 months (95% CI: 7.4-16.6), respectively. Interim analysis of overall survival based on 63% information fraction did not reach statistical significance but was supportive of the overall benefit risk assessment, FDA researchers noted in a press release about the findings.
The most common adverse reactions, including laboratory abnormalities, were decreased neutrophils, platelets, hemoglobin, lymphocytes, sodium, calcium, potassium, and appetite, stomatitis, nausea, diarrhea, fatigue, increased fasting glucose, high creatinine and ALT levels, rash, COVID-19 infection, and headache.
The recommended inavolisib dose is 9 mg taken orally once daily, with or without food, until disease progression or unacceptable toxicity.
References
- FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer.FDA. Press release. October 10, 2024. Accessed October 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive