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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


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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.

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