Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session 1

139O - Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC)


23 May 2020


Proffered Paper session 1


Rebecca Dent


Annals of Oncology (2020) 31 (suppl_2): S62-S82. 10.1016/annonc/annonc122


R. Dent1, A.M. Antunes De Melo e Oliveira2, S.J. Isakoff3, S. Im4, M. Espié5, S. Blau6, A.R. Tan7, C. Saura Manich2, M. Wongchenko8, N. Xu9, D. Bradley10, S. Reilly10, A. Mani11, S. Kim12

Author affiliations

  • 1 Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 2 Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 3 Division Of Hematology And Oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 4 Department Of Internal Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul/KR
  • 5 Breast Disease Center, Hospital Saint Louis, Paris/FR
  • 6 Oncology Division, Northwest Medical Specialties, Puyallup/US
  • 7 Department Of Solid Tumor And Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte/US
  • 8 Oncology Biomarker Development, Genentech, Inc., South San Francisco/US
  • 9 Biostatistics, Genentech, Inc., South San Francisco/US
  • 10 Pharma Development, Roche Products Ltd, Welwyn Garden City/GB
  • 11 Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 12 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 139O


In LOTUS (NCT02162719), adding the oral AKT inhibitor IPAT to 1st-line PAC for mTNBC improved progression-free survival (PFS; primary endpoint) [Kim, Lancet Oncol 2017]. The stratified PFS hazard ratio in the intent-to-treat (ITT) population was 0.60 (95% CI 0.37–0.98; p=0.037; median PFS 6.2 vs 4.9 mo with IPAT vs PBO, respectively), with an enhanced effect in patients (pts) with PIK3CA/AKT1/PTEN-altered tumours. Overall survival (OS) results were immature at the primary and updated analyses (deaths in 21% and 55% of pts, respectively). Here we report final results.


Eligible pts had measurable mTNBC previously untreated with systemic therapy. Pts were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval and tumour IHC PTEN status and randomised 1:1 to PAC 80 mg/m2 (d1, 8 & 15) plus either IPAT 400 mg or PBO (d1–21) q28d until disease progression (PD) or unacceptable toxicity. OS (ITT, PTEN-low and PI3K/AKT pathway-actived [PIK3CA/AKT1/PTEN-altered] populations) was a prespecified secondary endpoint.


By the final data cut-off (3 Sep 2019) all pts had discontinued treatment, predominantly because of PD. In the ITT population, median OS was numerically longer in the IPAT + PAC arm (Table). Similarly, median OS favoured IPAT + PAC vs PBO + PAC in the PTEN-low (n=48; 23.1 vs 15.8 mo) and PIK3CA/AKT1/PTEN-altered (n=42; 25.8 vs 22.1 mo) subgroups. There were few additional adverse events since previous reports and the safety profile of IPAT + PAC was unchanged. Table: 139O

Parameter PBO + PAC (n=62) IPAT + PAC (n=62)
Median duration of follow-up, mo (range) 16.0 (0.1–55.5) 19.0 (0.1–54.3)
Median treatment duration, mo (range) PBO/IPAT PAC 3.5 (0–27) 3.5 (0–27) 5.3 (0–43) a 5.1 (0–32) a
Adverse event leading to treatment discontinuation, n (%) PBO/IPAT PAC 1 (2) 6 (10) 4 (7) a 8 (13) a
OS events, n (%) 46 (74) 41 (66)
Median OS, mo (95% CI) 16.9 (14.6–24.6) 25.8 (18.6–28.6)
Stratified OS hazard ratio (95% CI) 0.80 (0.50–1.28)
1-year OS rate, % (95% CI) 68 (56–80) 83 (73–93)
Subsequent systemic anti-cancer therapy, n (%) 56 (90) 48 (77)

n=61 (safety population, all treated pts)


Final OS results show a numerical trend favouring IPAT + PAC; median OS exceeds 2 years with IPAT + PAC. Consistent with the previously observed PFS benefit, these findings support further evaluation of first-line IPAT + PAC for mTNBC in the ongoing IPATunity130 (NCT03337724) randomised phase III trial.

Clinical trial identification


Editorial acknowledgement

Medical writing support: Jennifer Kelly (Medi-Kelsey Ltd), funded by F Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F Hoffmann-La Roche Ltd.


F Hoffmann-La Roche Ltd.


R. Dent: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Eisai; Honoraria (self): Merck; Honoraria (self): AstraZeneca. M. Oliveira: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Philips Healthcare; Research grant/Funding (institution): Genentech; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Boehringer Ingelheim; Travel/Accommodation/Expenses: Grunenthal Group; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: GP Pharm. S.J. Isakoff: Honoraria (self), Research grant/Funding (institution): Genentech; Honoraria (self): Hengrui; Honoraria (self): Puma; Honoraria (self): Immunomedics; Honoraria (self): Myriad; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck. S-A. Im: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Eisai; Advisory/Consultancy: Medipacto; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Lilly. M. Espié: Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer. S. Blau: Spouse/Financial dependant, Husband is owner: All4cure. A.R. Tan: Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Celgene; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Eisai; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): G1Therapeutics; Research grant/Funding (institution): Daiichi-Sankyo. C. Saura: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self), Advisory/Consultancy: Puma; Honoraria (self), Advisory/Consultancy: Synthon; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Genentech. M. Wongchenko: Full/Part-time employment: Genentech/Roche; Shareholder/Stockholder/Stock options: Roche. N. Xu: Full/Part-time employment: Genentech/Roche; Shareholder/Stockholder/Stock options: Roche. D. Bradley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche; Licensing/Royalties, Named as an inventor on Roche/Genentech patent application: Roche. S-J. Reilly: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. A. Mani: Full/Part-time employment: Genentech/Roche; Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Named as an inventor on Roche/Genentech patent application: Roche/Genentech. S-B. Kim: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: Enzychem; Advisory/Consultancy: Dae Hwa Pharmaceutical Co. Ltd; Advisory/Consultancy: ISU Abxis; Advisory/Consultancy: Daiichi-Sankyo; Research grant/Funding (institution): Sanofi Aventis; Research grant/Funding (institution): Kyowa Kirin Inc; Research grant/Funding (institution): DongKook Pharma Co, Ltd.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings