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Overall survival (OS) update of the double-blind placebo (PBO)-controlled randomized phase 2 LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for locally advanced/metastatic triple-negative breast cancer (mTNBC).

Abstract

1008
Background: In LOTUS (NCT02162719), adding the oral AKT inhibitor IPAT to first-line PAC for mTNBC improved progression-free survival (PFS; primary endpoint) [Kim, Lancet Oncol 2017]. The stratified PFS hazard ratio (HR) in the intent-to-treat (ITT) population (n = 124) was 0.60 (95% CI 0.37–0.98; p = 0.037; median PFS 6.2 vs 4.9 months with IPAT vs PBO, respectively). In prespecified analyses of patients (pts) with PIK3CA/AKT1/PTEN-altered tumors, the unstratified PFS HR was 0.44 (95% CI 0.20–0.99; median 9.0 vs 4.9 months). We now report updated OS results in the ITT population after OS events in ~50% of pts. OS results in the PIK3CA/AKT1/PTEN-altered subgroup are immature. Methods: Eligible pts had measurable inoperable mTNBC previously untreated with systemic therapy. Pts were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval (6–12 months vs > 12 months vs not applicable) and tumor IHC PTEN status, and randomized 1:1 to PAC 80 mg/m2 (d1, 8, & 15) with either IPAT 400 mg or PBO (d1–21) q28d until progression or unacceptable toxicity. OS was a prespecified secondary endpoint. Results: The table shows results after 23 months’ follow-up (data cutoff 26 July, 2017). No new safety signals were seen. Conclusions: The previously observed PFS improvement with IPAT was followed by a trend toward improved OS (~5-month difference in the medians) at the updated OS analysis. Post-progression therapy was similar. These findings support further evaluation of first-line IPAT + PAC for mTNBC in the ongoing IPATunity130 (NCT03337724) randomized phase 3 trial. Final OS results from LOTUS are expected in 2019. Clinical trial information: NCT02162719.
ParameterIPAT + PAC (n = 62)PBO + PAC (n = 62)
OS events, n (%)33 (53)35 (56)
Median OS, months (95% CI)23.1 (18.6–28.1)18.4 (15.1–29.1)
OS hazard ratio (95% CI)Stratified: 0.62 (0.37–1.05)
Unstratified: 0.77 (0.48–1.25)
1-year OS rate, % (95% CI)83 (73–93)70 (58–81)
Post-progression systemic anti-cancer therapy, n (%)47 (76)55 (89)
    Immunotherapy7 (11)7 (11)
Adverse event leading to treatment discontinuation, n (%)a  
    IPAT/PBO4 (7)1 (2)
    PAC7 (11)6 (10)
an = 61 in IPAT + PAC arm

Publisher's Note

The 2018 ASCO Annual Meeting abstract by Dent et al entitled "Overall survival (OS) update of the double-blind placebo (PBO)-controlled randomized phase 2 LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for locally advanced/metastatic triple-negative breast cancer (mTNBC)." (J Clin Oncol 36, 2018 [suppl; abstr 1008]) was published online with errors.

Conflict of interest information for José Baselga, MD, PhD, has been updated to reflect previously undisclosed relationships. The corrected disclosures of potential conflicts of interest provided by the author are available with the online abstracts on JCO.org and ASCO.org.

This has been corrected as of January 10, 2019. The authors apologize for the errors.

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Journal of Clinical Oncology
Pages: 1008

History

Published in print: May 20, 2018
Published online: June 01, 2018

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Rebecca Dent
National Cancer Center, Singapore;
Seock-Ah Im
Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of (South);
Marc Espie
Hospital Saint Louis, Breast Disease Center, Paris, France;
Sibel Blau
Northwest Medical Specialties, Puyallup, WA;
Antoinette R. Tan
Levine Cancer Institute, Charlotte, NC;
Steven J. Isakoff
Massachusetts General Hospital, Boston, MA;
Mafalda Oliveira
Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain;
Cristina Saura
Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain;
Matthew Wongchenko
Genentech, Inc., South San Francisco, CA;
Amy V. Kapp
Genentech, Inc., South San Francisco, CA;
Wai Y. Chan
Genentech, Inc., South San Francisco, CA;
Stina M. Singel
Genentech, Inc., South San Francisco, CA;
Daniel J. Maslyar
Genentech, Inc., South San Francisco, CA;
Jose Baselga
Memorial Sloan Kettering Cancer Center, New York, NY;
Sung-Bae Kim
Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South);
National Cancer Center, Singapore; Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of (South); Hospital Saint Louis, Breast Disease Center, Paris, France; Northwest Medical Specialties, Puyallup, WA; Levine Cancer Institute, Charlotte, NC; Massachusetts General Hospital, Boston, MA; Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Genentech, Inc., South San Francisco, CA; Memorial Sloan Kettering Cancer Center, New York, NY; Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South)

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Rebecca Dent, Seock-Ah Im, Marc Espie, Sibel Blau, Antoinette R. Tan, Steven J. Isakoff, Mafalda Oliveira, Cristina Saura, Matthew Wongchenko, Amy V. Kapp, Wai Y. Chan, Stina M. Singel, Daniel J. Maslyar, Jose Baselga, Sung-Bae Kim
Journal of Clinical Oncology 2018 36:15_suppl, 1008-1008

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