Final results of the double-blind placebo-controlled randomized phase 2 LOTUS trial of first-line ipatasertib plus paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer
| العنوان: | Final results of the double-blind placebo-controlled randomized phase 2 LOTUS trial of first-line ipatasertib plus paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer |
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| المؤلفون: | Dent R, Oliveira M, Isakoff S, Im S, Espie M, Blau S, Tan A, Saura C, Wongchenko M, Xu N, Bradley D, Reilly S, Mani A, Kim S, LOTUS Investigators, LOTUS investigators |
| المصدر: | BREAST CANCER RESEARCH AND TREATMENT r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname |
| بيانات النشر: | SPRINGER, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Oral, Triple-negative breast cancer, AKT, Ipatasertib, First-line therapy, PI3K |
| الوصف: | Purpose In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN-altered tumors (FoundationOne next-generation sequencing [NGS] assay). We report final overall survival (OS) results. Methods Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m(2) (days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1-21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat [ITT], immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated [NGS PIK3CA/AKT1/PTEN-altered] populations) was a secondary endpoint. Results Median follow-up was 19.0 versus 16.0 months in the ipatasertib-paclitaxel versus placebo-paclitaxel arms, respectively. In the ITT population (n = 124), median OS was numerically longer with ipatasertib-paclitaxel than placebo-paclitaxel (hazard ratio 0.80, 95% CI 0.50-1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib-paclitaxel in the PTEN-low (n = 48; 23.1 vs 15.8 months; hazard ratio 0.83) and PIK3CA/AKT1/PTEN-altered (n = 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib-paclitaxel safety profile was unchanged. Conclusions Final OS results show a numerical trend favoring ipatasertib-paclitaxel and median OS exceeding 2 years with ipatasertib-paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity. |
| تدمد: | 0167-6806 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=RECOLECTA___::b5939b77c59216ad62d19e8bf3f795c4Test https://www.fundanet.incliva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=16260Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.RECOLECTA.....b5939b77c59216ad62d19e8bf3f795c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01676806 |
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