Back Back
Optimizing Tx of HRpos HER2neg MBC

CME

Optimizing Treatment for Patients With HR-Positive/HER2-Negative MBC

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit™

Released: March 24, 2025

Expiration: September 23, 2025

Sara A. Hurvitz
Sara A. Hurvitz, MD, FACP
CME/CE Information

Activity

Progress
1 2
Course Completed

INAVO120: Palbociclib + Fulvestrant ± Inavolisib for PIK3CA-Mutated MBC

The randomized phase III INAVO120 trial evaluated the efficacy and safety of adding inavolisib, a PI3 kinase pathway inhibitor, to a CDK4/6 inhibitor (palbociclib) and fulvestrant as first-line therapy for patients with HR-positive, HER2-negative locally advanced or MBC harboring a tumor PIK3CA mutation (NCT04191499). To be eligible for participation in INAVO120, patients should have received no prior systemic therapy for MBC and were required to have HbA1C less than 6.0% and a fasting glucose level less than 126 mg/dL. The eligibility criteria included disease progression during adjuvant ET or within 12 months of completing adjuvant ET with an AI or tamoxifen. Patients with type 2 diabetes requiring ongoing systemic therapy at the time of enrolment or those with any history of type 1 diabetes were excluded from participating. The primary endpoint was PFS by investigator assessment with secondary endpoints including OS, response, quality of life parameters, and safety. 

In total, 325 patients were randomized to receive inavolisib plus palbociclib and fulvestrant (n = 161) or placebo plus palbociclib and fulvestrant (n = 164).15 

Download

INAVO120: PFS

There was a statistically significant improvement in the median PFS with the triplet regimen of inavolisib plus palbociclib and fulvestrant (15.0 months) compared with the doublet regimen of palbociclib plus fulvestrant (7.3 months) (HR: 0.43; 95% CI: 0.32-0.59; P <.001). 

Download

INAVO120: PFS by Subgroups

The analysis of PFS according to subgroups demonstrated a generally consistent benefit in favor of the triplet regimen compared to the doublet regimen, including a PFS benefit regardless of the presence or absence of visceral or liver metastases at trial enrollment.

Download

INAVO120: OS

At the time of interim OS analysis, after a median follow-up of 21.3 months (inavolisib arm) and 21.5 months (placebo arm), the median OS was not reached in the inavolisib arm vs 31.1 months in the placebo arm (HR: 0.64; 95% CI: 0.43-0.97; P = .03). Landmark analysis showed that the 18-month OS rate was 73.7% in the inavolisib arm vs 67.5% in the placebo arm. However, the P-value for OS did not cross the predefined boundary for statistical significance of P <.0098.

Download

INAVO120: AEs

Patients who received inavolisib-based therapy (triplet regimen) had similar rates of any grade and grade 3/4 neutropenia compared to those who received the doublet regimen. However, compared with patients on the placebo arm, there was a higher rate of grade 3/4 thrombocytopenia (14.2% vs 4.3%), anemia (6.2% vs 1.9%), hyperglycemia (5.6% vs 0), diarrhea (3.7% vs 0), and stomatitis and mucosal inflammation (5.6% vs 0) among patients who received inavolisib compared to those who did not. Any grade diarrhea was observed in 48.1% of patients who received inavolisib compared with 16% of those who did not. Of note, hyperglycemia of any grade was observed 58.6% of patients who received inavolisib compared with 8.6% of those who did not. The relatively low rate of grade 3 or higher hyperglycemia on the inavolisib arm (5.6%) is likely due to the strict trial entry criteria relating to glucose levels.

Based on the efficacy and safety results from the phase III INAVO120 trial, inavolisib is indicated in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or MBC, as detected by an FDA-approved test, following recurrence on or after completing adjuvant ET.29 It is important to keep in mind that for patients to be eligible to receive inavolisib in combination with palbociclib and fulvestrant (INAVO120 regimen), their HbA1C should be less than 6.0% and fasting glucose less than 126 mg/dL. Thus, before prescribing inavolisib plus palbociclib and fulvestrant, the HbA1C and fasting glucose levels should be tested at baseline.

Download
BACK | NEXT