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| Ref Type | Journal Article | ||||||||||||
| PMID | (39058425) | ||||||||||||
| Authors | Dent RA, Kim SB, Oliveira M, Barrios C, O'Shaughnessy J, Isakoff SJ, Saji S, Freitas-Junior R, Philco M, Bondarenko I, Lian Q, Bradley D, Hinton H, Wongchenko MJ, Reilly SJ, Turner N | ||||||||||||
| Title | Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial. | ||||||||||||
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| Abstract Text | In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population.In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1-21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS.Between February 2018 and April 2020, 255 patients were randomized (168 to ipatasertib, 87 to placebo). At the primary analysis, there was no significant difference between treatment arms in PFS [hazard ratio 1.02, 95% confidence interval (CI), 0.71-1.45; median 7.4 months with ipatasertib vs. 6.1 months with placebo]. The final analysis showed no difference in overall survival between treatment arms (hazard ratio 1.08, 95% CI, 0.73-1.58; median 24.4 vs. 24.9 months, respectively). Ipatasertib was associated with more grade ≥3 diarrhea (9% vs. 2%) and adverse events leading to dose reduction (39% vs. 14%) but similar incidences of grade ≥3 adverse events (51% vs. 46%). Exploratory subgroup analyses by PAM50 and Burstein gene expression showed inconsistent results.Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered advanced TNBC. Biomarkers for benefit from PI3K/AKT pathway inhibition in TNBC remain poorly understood. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PIK3CA act mut | triple-receptor negative breast cancer | no benefit | Ipatasertib + Paclitaxel | Phase III | Actionable | In a Phase III trial (IPATunity130), the addition of Ipatasertib (GDC-0068) to treatment with Abraxane (paclitaxel) did not result in improved median progression-free survival (7.4 mo vs 6.1 mo, HR=1.02, p=0.92), median overall survival (24.4 mo vs 24.9 mo, HR=1.08), objective response rate (39% vs 35%) or clinical benefit rate (47% vs 45%) in patients with metastatic triple-negative breast cancer harboring PIK3CA and/or AKT activating mutations or PTEN inactivating mutations (PMID: 39058425; NCT03337724). | 39058425 |
| PTEN inact mut | triple-receptor negative breast cancer | no benefit | Ipatasertib + Paclitaxel | Phase III | Actionable | In a Phase III trial (IPATunity130), the addition of Ipatasertib (GDC-0068) to treatment with Abraxane (paclitaxel) did not result in improved median progression-free survival (7.4 mo vs 6.1 mo, HR=1.02, p=0.92), median overall survival (24.4 mo vs 24.9 mo, HR=1.08), objective response rate (39% vs 35%) or clinical benefit rate (47% vs 45%) in patients with metastatic triple-negative breast cancer harboring PIK3CA and/or AKT activating mutations or PTEN inactivating mutations (PMID: 39058425; NCT03337724). | 39058425 |