FDA Approves Inavolisib With Palbociclib and Fulvestrant for Breast Cancer

The FDA approved inavolisib (Itovebi; Genentech Inc) in combination with palbociclib (Ibrance; Pfizer) and fulvestrant (Faslodex; AstraZeneca) for the treatment of endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, human epidermal growth-factor receptor 2-negative, locally advanced or metastatic breast cancer. The combination can be used following recurrence on or after completing adjuvant endocrine therapy.¹

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Furthermore, the FDA also approved the FoundationOne Liquid CDx assay as a companion diagnostic device to identify patients who would benefit from treatment with inavolisib with palbociclib and fulvestrant.¹

The approval was based on the INAVO120 trial (NCT04191499), which was a randomized, double-blinded, multicenter trial enrolling 325 patients with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer. Individuals included had disease progression during or within 12 months of completing adjuvant endocrine therapy and had not received prior systemic therapy for locally advanced or metastatic disease, according to the release. Investigators randomized treatment to either the study combination or the placebo with palbociclib and fulvestrant. Inavolisib and the placebo were administered orally on days 1 through 28 of each 28-day cycle, palbociclib was administered orally on days 1 through 21 of each 28-day cycle, and fulvestrant was administered intramuscularly approximately every 4 weeks.^1,2

The primary end point was progression free survival (PFS) up to 3.7 years, and secondary end points included percentage of individuals with objective response rate (ORR) up to approximately 6 years, percentage of patients with best overall response rate up to 6 years, duration of response (DOR) up to 6 years, percentage of participants with clinical benefit rate up to 6 years, overall survival up to 6 years, and number of patients with adverse events up to 6 years, according to the clinical trial information.²

Median PFS was 15 months in the combination arm and 7.3 months in the placebo arm, with the ORR reaching 58% and 25%, respectively. Median DOR was 18.4 months and 9.6 months, respectively. Additionally, the interim analysis of OS did not yet reach statistical significance.¹

In results presented at the American Society of Clinical Oncology Annual Meeting 2024, PFS2 reached 24 months compared to 15.2 months for the combination and placebo, respectively, and time to first chemotherapy was not yet reached in the combination group but reached 15 months in the placebo group. The most common adverse reactions (≥20%) included decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decrease lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache.^1,3

The combination was previously granted priority review and breakthrough designation by the FDA.¹

REFERENCES

1. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. FDA. October 10, 2024. Accessed October 10, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive

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 identification: NCT04191499. Updated October 9, 2024. Accessed October 10, 2024. https://clinicaltrials.gov/study/NCT04191499

3. Juric D, Kalinsky K, Turner NC, Jhaveri KL, et al. First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses. Journal of Oncology. 2024. doi:https://doi.org/10.1200/JCO.2024.42.16_suppl.1003