Drugs Xagena
The Food and Drug Administration ( FDA ) has approved Itovebi ( Inavolisib ), with Palbociclib and Fulvestrant 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.
FDA has also approved the FoundationOne Liquid CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with Inavolisib with Palbociclib and Fulvestrant.
Efficacy was evaluated in INAVO120, a randomized, double-blind, placebo-controlled, multicenter trial in 325 patients with endocrine-resistant, PIK3CA-mutated HR-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during or within 12 months of completing adjuvant endocrine therapy and who had not received prior systemic therapy for locally advanced or metastatic disease.
Primary endocrine resistance was defined as relapse while on the first 2 years of adjuvant endocrine therapy and secondary endocrine resistance was defined as relapse while on adjuvant endocrine therapy after at least 2 years or relapse within 12 months of completing adjuvant endocrine therapy.
Patients were randomized 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. Randomization was stratified by presence of visceral disease (yes or no), endocrine resistance (primary or secondary), and geographic region (North America/Western Europe, Asia, other).
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 15.0 months (95% CI: 11.3, 20.5) in the Inavolisib + Palbociclib + Fulvestrant arm and 7.3 months (95% CI: 5.6, 9.3) in the placebo + Palbociclib + Fulvestrant arm (hazard ratio 0.43 [95% CI: 0.32, 0.59] p-value less than 0.0001).
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 with a hazard ratio of 0.64 (95% CI: 0.43, 0.97).
The most common adverse reactions (greater than or equal to 20%), including laboratory abnormalities, were decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased ALT, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, 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. ( Xagena )
Source: FDA, 2024
XagenaMedicine_2024
