The long-term safety profile of inavolisib plus palbociclib and fulvestrant for patients with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer who relapsed during or after 12 months of completing adjuvant endocrine therapy at ≥1 year and ≥2 years was consistent with both the previously reported safety profile of the safety analysis set in the INAVO120 trial and the long-term safety data of the phase 1 GO39374 trial.

The INAVO120 trial randomized 325 patients to receive either 9 mg of inavolisib or placebo once daily on days 1 to 28 of each cycle followed by palbociclib and fulvestrant. The primary end point of this study was investigator-assessed progression-free survival (PFS) with secondary end points including overall survival and confirmed objective response rate. As previously reported, the primary end point was met, with a median PFS of 15.0 months in the inavolisib arm and 7.3 months in the placebo arm. This analysis reports on long-term safety data from the inavolisib arm.

The safety analysis set (SAS) includes all patients who received ≥ 1 dose of the study treatment and the full analysis set (FAS) includes all patients randomized to receive the study treatment.

This analysis reports on all patients in the inavolisib arm who received treatment for ≥ 1 year, and who received treatment for ≥2 years. There were 162 patients randomized to inavolisib in the SAS and 161 in the FAS. In both the SAS there were 69 patients on the study treatment for ≥1 year and 27 on study treatment for ≥2 years. The median treatment durations for inavolisib were 21.6 months in the ≥ 1 year cohort and 29.9 months in the ≥ 2 year cohort.

In the ≥ 1 year cohort there were 88.4% of patients who experienced a grade 3/4 adverse event and in the ≥ 2 year cohort there were 88.9%. The most common adverse events in the ≥ 1 year cohort were neutropenia, neutrophil count decreased, leukopenia, and white blood cell count decreased. The most common adverse events in the ≥ 2 year cohort were neutropenia, neutrophil count decreased, anemia, leukopenia, white blood cell count decreased, and anal fistula. There were 27.5% and 44.4% of patients, respectively, who experienced a serious adverse event. Grade 5 adverse events were reported in 2,9% of patients in the ≥ 1 year cohort and 0% of patients in the ≥2 year cohort. No patient discontinued from inavolisib due to an adverse event in either cohort. There were inavolisib dose interruptions due to adverse events among 79.7% and 85.2% of patients, respectively, with the most common adverse event leading to dose interruptions being hyperglycemia. There were inavolisib dose reductions due to adverse events among 18.8% and 14.8% of patients, respectively, with the most common adverse events leading to dose reductions being hyperglycemia and stomatitis in the ≥ 1 year cohort, and diarrhea, stomatitis, papulopustular rosacea, platelet count decrease, hyperglycemia, and myalgia in the ≥2 year cohort.

Study authors concluded that the long-term safety profile of inavolisib plus palbociclib and fulvestrant among patients who were on the treatment for ≥ 1 year and ≥ 2 year “was consistent with the INAVO120 SAS population reported previously.” They added that there were no new or unexpected adverse events observed.

Source:

Saura C, Turner N, Jhaveri KE, et al. First-line inavolisib/placebo + palbociclib + fulvestrant in PIK3CA-mutated, hormone receptor+, HER2– locally advanced/metastatic breast cancer w/ relapse during/within 12 months of adjuvant endocrine therapy completion: INAVO120 long-term safety. Presented at San Antonio Breast Cancer Symposium. Dec 10-13, 2024; San Antonio, TX. Abstract: SESS-1786