@article{c18c7662f63d41dfb1b483ac6709a44e,
title = "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",
abstract = "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/m2 (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.",
keywords = "First-line therapy, Ipatasertib, Oral, PI3K/AKT, Triple-negative breast cancer",
author = "{on behalf of the LOTUS investigators} and Rebecca Dent and Mafalda Oliveira and Isakoff, {Steven J.} and Im, {Seock Ah} and Marc Espi{\'e} and Sibel Blau and Tan, {Antoinette R.} and Cristina Saura and Wongchenko, {Matthew J.} and Na Xu and Denise Bradley and Reilly, {Sarah Jayne} and Aruna Mani and Kim, {Sung Bae} and Lee, {K. S.} and Sohn, {J. H.} and Kim, {J. H.} and Seo, {J. H.} and Kim, {J. S.} and S. Park and M. Velez and S. Dakhil and S. Hurvitz and V. Valero and G. Vidal and R. Figlin and Allison, {M. A.K.} and D. Chan and M. Cobleigh and V. Hansen and N. Iannotti and W. Lawler and M. Salkini and L. Seigel and G. Romieu and M. Debled and C. Levy and A. Hardy-Bessard and S. Guiu and Estevez, {L. Garcia} and R. Villanueva and Martin, {A. Gonzalez} and Rovira, {P. Sanchez} and A. Monta{\~n}o and Plaza, {M. I.Calvo} and Saenz, {J. A.Garc{\'i}a} and I. Garau and B. Bermejo and Alonso, {E. Vega} and Wang, {H. C.}",
note = "Funding Information: We are grateful to the patients who participated in the trial, their families, and the investigators and staff at the 44 participating centers. The LOTUS trial was sponsored by Roche/Genentech. Medical writing assistance for this manuscript was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd, Ashbourne, UK), funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Collaborators: K.S. Lee, J.H. Sohn, J.H. Kim, J.H. Seo, J.S. Kim, S. Park (South Korea); M. Velez, S. Dakhil, S. Hurvitz, V. Valero, G. Vidal, R. Figlin, M.A.K. Allison, D. Chan, M. Cobleigh, V. Hansen, N. Iannotti, W. Lawler, M. Salkini, L. Seigel (USA); G. Romieu, M. Debled, C. Levy, A. Hardy-Bessard, S. Guiu (France); L. Garcia Estevez, R. Villanueva, A. Gonzalez Martin, P. Sanchez Rovira, A. Monta{\~n}o, M.I. Calvo Plaza, J.A. Garc{\'i}a Saenz, I. Garau, B. Bermejo, E. Vega Alonso (Spain); H-C. Wang, C-S. Huang, S-C. Chen, Y-H. Chen, L-M. Tseng (Taiwan); A. Wong, C.S.P. Ang (Singapore); M. De Laurentiis, P.F. Conte, F. De Braud, F. Montemurro, L. Gianni (Italy); L. Dirix (Belgium). Funding Information: R Dent has received honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. M Oliveira has received honoraria from Roche, has served in a consultancy/advisory role for Roche/Genentech, GlaxoSmithKline, and Puma, and has received travel/accommodation/expenses from Roche, Novartis, Gr{\"u}nenthal Group, Pierre Fabre, and GP Pharm; her institution has received research funding from AstraZeneca, Philips Healthcare, Genentech, Roche, Novartis, Immunomedics, Seattle Genetics, GSK, Boehringer Ingelheim, and Puma Biotechnology. SJ Isakoff has received honoraria from Genentech, Hengrui, Puma, Immunomedics, Myriad and OncoPep, Inc.; his institution has received research funding from Genentech, PharmaMar, AstraZeneca, and Merck. S-A Im has served in a consultancy/advisory role for AstraZeneca, Amgen, Eisai, Lilly, MedPacto, Novartis, Daiichi-Sankyo, Pfizer, and Roche; his institution has received research funding from AstraZeneca, Pfizer, and Roche. M Espi{\'e} has received research funding from Roche, Novartis, and Pfizer. S Blau reports that her husband is the owner of the company All4Cure. AR Tan has served in a consultancy/advisory role for Immunomedics, Celgene, Pfizer, Genentech/Roche, Novartis, AbbVie, and Eisai; her institution has received research funding from Merck, Pfizer, Tesaro, Genentech/Roche, G1 Therapeutics, and Daiichi-Sankyo. C Saura has received honoraria from AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Roche, Genomic Health, Novartis, Pfizer, Pierre Fabre, Puma, and Synthon, has served in a consultancy/advisory role for AstraZeneca, Eisai, Roche, Genomic Health, Novartis, Pfizer, Puma, Sanofi, and Synthon, and has received research funding from Genentech and AstraZeneca. MJ Wongchenko, N Xu, and A Mani are employed by Genentech/Roche and hold shares in Roche. D Bradley is employed by Roche Products Ltd, holds shares in Roche, and is named as an inventor on a Roche/Genentech patent application. S-J Reilly is employed by Roche Products Ltd and holds shares in Roche. S-B Kim has served in a consulting/advisory role for Novartis, AstraZeneca, Lilly, Enzychem Lifesciences, Dae Hwa Pharmaceutical Co. Ltd, ISU Abxis, and Daiichi-Sankyo and has received research funding from Novartis, Sanofi Aventis, Kyowa Kirin Inc, and DongKook Pharma Co, Ltd. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",
year = "2021",
month = sep,
doi = "10.1007/s10549-021-06143-5",
language = "English",
volume = "189",
pages = "377--386",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "2",
}
