- Sibylle Loibl (Neu-Isenburg, Germany)
Introduction
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)
- Rebecca Dent (Singapore, Singapore)
- Rebecca Dent (Singapore, Singapore)
- Ana Mafalda Antunes De Melo e Oliveira (Barcelona, Spain)
- Steven J. Isakoff (Boston, MA, United States of America)
- Seock-Ah Im (Seoul, Korea, Republic of)
- Marc Espié (Paris, France)
- Sibel Blau (Puyallup, United States of America)
- Antoinette R. Tan (Charlotte, United States of America)
- Cristina Saura Manich (Barcelona, Spain)
- Matthew Wongchenko (South San Francisco, United States of America)
- Na Xu (South San Francisco, United States of America)
- Denise Bradley (Welwyn Garden City, United Kingdom)
- Sarah-Jayne Reilly (Welwyn Garden City, United Kingdom)
- Aruna Mani (South San Francisco, United States of America)
- Sung-Bae Kim (Seoul, Korea, Republic of)
Abstract
Background
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.
Methods
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.
Results
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. n=61 (safety population, all treated pts)
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) Adverse event leading to treatment discontinuation, n (%) PBO/IPAT PAC 1 (2) 6 (10) 4 (7) 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)
Conclusions
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
NCT02162719.
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.
Funding
F Hoffmann-La Roche Ltd.
Disclosure
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.
140O - Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial
- Jean-Pierre Ayoub (Montreal, Canada)
- Michael L. Friedlander (Randwick, Australia)
- Veronique C. Dieras (Rennes, France)
- Hans Wildiers (Leuven, Belgium)
- Banu Arun (Houston, TX, United States of America)
- Hyo S. Han (Tampa, United States of America)
- Shannon Puhalla (Pittsburgh, United States of America)
- Yaroslav Shparyk (Lviv, Ukraine)
- Erik H. Jakobsen (Vejle, Denmark)
- Madan G. Kundu (North Chicago, United States of America)
- Meijing Wu (North Chicago, United States of America)
- Christine Ratajczak (North Chicago, United States of America)
- David Maag (North Chicago, United States of America)
- Bella Kaufman (Tel Aviv-Yafo, Israel)
Abstract
Background
In BROCADE3 (NCT02163694), addition of the PARP1/2 inhibitor veliparib (Vel) to carboplatin-paclitaxel (C-P) significantly prolonged progression-free survival (PFS) in patients (pts) with HER2-negative locally advanced/metastatic gBRCA-associated breast cancer (BC; hazard ratio=0.71 [95% CI 0.57, 0.88], P=.002). Here we report efficacy and safety in hormone receptor-positive (HR+) and triple-negative BC (TNBC) subgroups separately.
Methods
Pts with ≤2 prior lines of cytotoxic therapy for metastatic BC were randomized 2:1 to Vel (120 mg PO BID) + C-P or placebo (Pbo) + C-P. Vel-Pbo was given on days (d) –2 to 5, C (AUC 6 mg/mL/min IV) on d 1, and P (80 mg/m2 IV) on d 1, 8, and 15 (21-d cycles). Pts who discontinued C and P prior to progression (at investigator discretion) received blinded single-agent Vel or Pbo (300–400 mg BID) until progression. Primary endpoint was investigator-assessed PFS. Analysis of PFS in subgroups defined by hormone receptor status was preplanned. Analyses of PFS and overall survival (OS) were stratified by prior platinum status.
Results
Among the 509 pts in the intent-to-treat population, 266 (52%) were HR+ and 243 (48%) had TNBC. PFS and OS results in each subgroup are presented in the table below. Adverse events (not related to progression) led to study drug discontinuation in 8.0%/3.3% of HR+ pts and 10.5%/7.5% of TNBC pts in the Vel + C-P and Pbo + C-P arms, respectively. On the basis of stratified log-rank test. P values are nominal. BICR, blinded independent central review; C-P, carboplatin plus paclitaxel; ER, estrogen receptor; HR+, hormone receptor positive (ER and/or PgR); INV, investigator; m, median; NR, not reached; OS, overall survival; PFS, progression-free survival; PgR, progesterone receptor; TNBC, triple-negative breast cancer.
HR+ Subgroup TNBC Subgroup Veliparib + C-P n=174 Placebo + C-P n=92 Veliparib + C-P n=163 Placebo + C-P n=80 mPFS per INV, mo (95% CI) 13.0 (12.1, 16.6) 12.5 (10.2, 13.2) 16.6 (12.3, 22.7) 14.1 (11.0, 15.8) PFS hazard ratio (95% CI) 0.69 (0.52, 0.93) 0.72 (0.52, 1.00) PFS rate at 2 years, % (95% CI) 27.5 (20.6, 34.8) 15.3 (8.2, 24.5) 40.4 (32.3, 48.4) 25.0 (15.3, 35.9) PFS rate at 3 years, % (95% CI) 17.5 (11.2, 25.0) 8.6 (3.3, 17.0) 35.3 (27.2, 43.6) 13.0 (5.3, 24.2) mPFS per BICR, mo (95% CI) 18.7 (14.5, 22.9) 12.6 (11.4, 16.5) 21.0 (16.0, 29.3) 14.5 (12.5, 19.7) PFS hazard ratio (95% CI) 0.68 (0.48, 0.97) 0.71 (0.49, 1.03) PFS rate at 2 years, % (95% CI) 39.5 (30.6, 48.2) 25.5 (13.9, 39.0) 47.4 (38.3, 56.0) 29.0 (17.7, 41.3) PFS rate at 3 years, % (95% CI) 35.1 (26.0, 44.3) 18.6 (8.1, 32.4) 39.7 (30.2, 48.9) 20.9 (9.5, 35.3) mOS (mo, 95% CI) [interim] 32.4 (26.5, 37.9) 27.1 (22.9, 35.2) 35.0 (24.9, NR) 30.0 (24.5, NR) OS hazard ratio (95% CI) 0.96 (0.68, 1.36) 0.92 (0.62, 1.36)
Conclusions
The addition of Vel to C-P improved PFS in gBRCA pts with HR+ BC and TNBC. In both subgroups, benefit of Vel was durable with an increase in proportion of pts progression free at 2 and 3 years compared with Pbo.
Clinical trial identification
NCT02163694.
Editorial acknowledgement
Medical writing support was provided by Mary L. Smith, PhD, CMPP, from Aptitude Health, Atlanta, GA, and funded by AbbVie.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
J-P. Ayoub: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Boston Biomedical; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Puma; Advisory/Consultancy: Roche. M.L. Friedlander: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Inc. Steering Committee: MSD; Advisory/Consultancy, Non-remunerated activity/ies: AbbVie; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Novartis; Research grant/Funding (self): BeiGene. V.C. Dieras: Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: MSD; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: AstraZeneca. H. Wildiers: Honoraria (institution): Roche/Genentech; Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Lilly; Honoraria (institution): Novartis; Honoraria (institution): AbbVie; Honoraria (institution): Vifor Pharma; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Celldex Therapeutics; Honoraria (institution): Janssen-Cilag; Honoraria (institution): TRM Oncology; Honoraria (institution): PUMA Biotechnology; Honoraria (institution): Orion Corporation; Research grant/Funding (institution): Roche; Travel/Accommodation/Expenses: Roche. B. Arun: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Invitae; Non-remunerated activity/ies: AbbVie. H.S. Han: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Prescient; Research grant/Funding (institution): Horizon; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): TapImmune; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution), Grant: Department of Defense; Speaker Bureau/Expert testimony: Lilly. S. Puhalla: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy: MedImmune; Advisory/Consultancy: Celldex; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: NanoString; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Covance-Bayer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Medivation. Y. Shparyk: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Roche; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Boehringer Ingelheim. E.H. Jakobsen: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Puma; Non-remunerated activity/ies, principal investigator BROCADE3 trial: AbbVie. M.G. Kundu: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. M. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. C. Ratajczak: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. D. Maag: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. B. Kaufman: Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Roche; Honoraria (self), Steering committee: AbbVie.
Invited discussant abstracts: 139O and 140O
- Suzette Delaloge (Villejuif, France)
- Suzette Delaloge (Villejuif, France)
183O - Use of physical activity (PA) and supportive care (SC) among patients (pts) with early breast cancer (BC) reporting cancer-related fatigue (CRF)
- Antonio Di Meglio (Villejuif, France)
- Antonio Di Meglio (Villejuif, France)
- Cecile Charles (Villejuif, France)
- Elise Martin (Villejuif, France)
- Julie Havas (Villejuif, France)
- Arnauld S. Gbenou (Villejuif, France)
- Anne-Laure Martin (Paris, France)
- Sibille Everhard (Paris, France)
- Enora Laas (Paris, France)
- Olivier Tredan (Lyon, France)
- Laurence Vanlemmens (Lille, France)
- Christelle Jouannaud (Reims, France)
- Christelle Levy (Caen, France)
- Olivier Rigal (Rouen, France)
- Marion Fournier (Bordeaux, France)
- Patrick Soulie (Angers, France)
- Agnes Dumas (Paris, France)
- Gwenn Menvielle (Paris, France)
- Fabrice André (Villejuif, France)
- Sarah Dauchy (Villejuif, France)
- Ines Vaz Luis (Villejuif, Portugal)
Abstract
Background
CRF is highly prevalent in early BC. PA and psychosocial interventions were proven to be effective in several meta-analyses and are recommended management strategies for CRF. Some randomized trials support the use of acupuncture, while there are no data showing benefits of homeopathy for CRF. We aimed to assess use of PA and SC among pts with early BC.
Methods
Pts with stage I-III BC were prospectively included from the CANTO cohort (NCT01993498). Baseline CRF was evaluated shortly after treatment using EORTC-C30 for global CRF and EORTC-FA12 for its physical, emotional and cognitive domains. A score of 40 or higher defined CRF as severe (Abrahams HJ, Ann Oncol 2016). Data on adherence to PA recommendations (10 MET-hours/week or more) and SC consultations with a psychologist, acupuncturist or homeopath were collected in CANTO and therefore served as outcomes. Multivariable logistic regression examined associations between baseline CRF status (severe v not) and use of PA or SC consultations over the 12 months after baseline CRF assessment. Covariates included socio-demographics and psychological distress.
Results
Among 9691 pts included in CANTO, 6282 had available data on PA and 7598 on SC consultations. At baseline, 36% pts reported severe global CRF, and 36%, 23% and 14% pts reported severe physical, emotional and cognitive CRF, respectively. Overall, 64% pts were adherent to PA recommendations and only 10% pts saw a psychologist, whereas 8% saw an acupuncturist and 7% a homeopath. Pts reporting severe global CRF (v not severe) were less likely to adhere to PA recommendations (60% v 67%; adjusted odds ratio [aOR] 0.82, 95% CI 0.72-0.94), but more likely to see a psychologist (14% v 7%; aOR 1.31, 1.07-1.59), acupuncturist (10% v 6%; aOR 1.51, 1.22-1.86) or homeopath (10% v 6%; aOR 1.55, 1.25-1.92). There were differences in use of PA and SC consultations by CRF domain: pts reporting severe physical CRF showed lower adherence to PA (59% v 67%; aOR 0.73, 0.63-0.85), whereas pts with severe emotional CRF were more prone to psychology consultations (17% v 8%; aOR 1.41, 1.10-1.82).
Conclusions
This large study calls for the need to optimize and personalize the uptake of recommendations to manage CRF among pts with early BC.
Clinical trial identification
NCT01993498.
Legal entity responsible for the study
Unicancer.
Funding
Agence nationale de la Recherche (ANR-10-COHO-0004); Susan G. Komen (CCR17483507 to I. Vaz-Luis); Odyssea; Gustave Roussy.
Disclosure
A. Di Meglio: Honoraria (self): ThermoFisher. I. Vaz-Luis: Honoraria (self): Novartis; Honoraria (self): Kephren; Honoraria (self): AstraZeneca; Advisory/Consultancy: Ipsen; Honoraria (self): Amgen. All other authors have declared no conflicts of interest.
Invited discussant abstract: 183O
- Dario Trapani (Milan, Italy)
- Dario Trapani (Milan, Italy)