| Abstract: |
Background In the phase 3, double-blind, randomized INAVO120 trial, treatment with inavolisib plus palbociclib-fulvestrant led to a significant progression-free survival benefit, as compared with placebo plus palbociclib-fulvestrant, among patients with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after completion of adjuvant endocrine therapy. Methods We randomly assigned patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who had had disease recurrence or progression during or within 12 months after completion of adjuvant endocrine therapy to receive inavolisib plus palbociclib-fulvestrant (inavolisib group) or placebo plus palbociclib-fulvestrant (placebo group). In the current report, we provide the results of the final analysis of overall survival, including updated data on efficacy and safety. Results A total of 161 patients were assigned to the inavolisib group, and 164 to the placebo group. After a median follow-up of 34.2 months in the inavolisib group and 32.3 months in the placebo group, the median overall survival was 34.0 months (95% confidence interval [CI], 28.4 to 44.8) with inavolisib and 27.0 months (95% CI, 22.8 to 38.7) with placebo (hazard ratio for death, 0.67; 95% CI, 0.48 to 0.94; P=0.02 [prespecified boundary for statistical significance, P<0.0469]). An objective response occurred in 62.7% (95% CI, 54.8 to 70.2) of patients in the inavolisib group and 28.0% (95% CI, 21.3 to 35.6) of those in the placebo group (P<0.001). The updated hazard ratio for disease progression or death was 0.42 (95% CI, 0.32 to 0.55). Adverse events led to discontinuation of inavolisib in 6.8% of patients and discontinuation of placebo in 0.6%. The incidence of hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects (e.g., diarrhea), and ocular toxic effects (e.g., dry eye and blurred vision) was higher with inavolisib than with placebo. Conclusions Treatment with inavolisib plus palbociclib-fulvestrant led to a significant overall survival benefit, as compared with placebo plus palbociclib-fulvestrant. Hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects, and ocular toxic effects were reported more frequently with inavolisib than with placebo. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.). © 2025 Massachusetts Medical Society. |
| Keywords: |
adult; cancer chemotherapy; cancer survival; clinical article; controlled study; aged; middle aged; gene mutation; major clinical study; overall survival; genetics; mutation; clinical trial; mortality; neutropenia; drug efficacy; drug safety; pyridines; cancer patient; outcome assessment; follow up; antineoplastic agent; progression free survival; phase 2 clinical trial; breast cancer; anemia; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; incidence; epidermal growth factor receptor 2; breast neoplasms; retrospective study; multicenter study; breast tumor; receptor, erbb-2; phase 3 clinical trial; piperazines; kaplan meier method; drug therapy; piperazine derivative; double blind procedure; double-blind method; alopecia; imidazoles; fulvestrant; imidazole derivative; pyridine derivative; progression-free survival; kaplan-meier estimate; clinical outcome; overall response rate; hematology/oncology; oxazoles; pik3ca protein, human; phosphatidylinositol 4,5 bisphosphate 3 kinase; humans; human; male; female; article; palbociclib; oxazole derivative; class i phosphatidylinositol 3-kinases; treatments in oncology; inavolisib; oxazepines; 2-(3-(2-(1-isopropyl-3-methyl-1h-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1h-pyrazol-1-yl)-2-methylpropanamide; oxazepine derivative; pik3ca -mutated advanced breast cancer
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