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Poster display - Cocktail

400 - Ribociclib (RIB) + endocrine therapy (ET) in Japanese women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC)


24 Nov 2018


Poster display - Cocktail


Cytotoxic Therapy;  Targeted Therapy

Tumour Site

Breast Cancer


Norikazu Masuda


Annals of Oncology (2018) 29 (suppl_9): ix13-ix20. 10.1093/annonc/mdy428


N. Masuda1, S. Noguchi2, T. Ishikawa3, T. Aruga4, S.J. Kim2, T. Toyama5, T. Saeki6, M. Saito7, T. Yamanaka8, J. Watanabe9, S. Nakamura10, M. Takahashi11, K. Inoue12, I. Gounaris13, Y. Han13, T.S. Samant13, M. Gazdoiu13, Y. Ito14

Author affiliations

  • 1 Medical Oncology, NHO Osaka National Hospital, 540-0006 - Osaka/JP
  • 2 Medical Oncology, Osaka University Hospital, Osaka/JP
  • 3 Medical Oncology, Tokyo Medical University Hospital, Tokyo/JP
  • 4 Medical Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo/JP
  • 5 Medical Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya/JP
  • 6 Medical Oncology, Saitama Medical University International Medical Center, Saitama/JP
  • 7 Medical Oncology, Juntendo University Hospital, Tokyo/JP
  • 8 Medical Oncology, Kanagawa Cancer Center, Yokohama/JP
  • 9 Medical Oncology, Shizuoka Cancer Center, Nagaizumi/JP
  • 10 Breast Center, Showa University Hospital, Tokyo/JP
  • 11 Medical Oncology, National Hospital Organization Hokkaido Cancer Center, Hokkaido/JP
  • 12 Medical Oncology, Saitama Cancer Center, Saitama/JP
  • 13 Novartis Oncology, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 14 Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo/JP


Abstract 400


MONALEESASIA (NCT02333370) is an ongoing Phase Ib dose-escalation (RIB + letrozole [LET]) and dose-expansion (RIB + LET, fulvestrant [FUL], or tamoxifen [TAM]) study in Asian patients (pts) with HR+, HER2– ABC; here we present results from Japanese pts.


In the dose escalation, postmenopausal pts (no prior therapy for ABC) received RIB (starting dose 400 mg/day [d]; 3 weeks on/1 week off) + LET (2.5 mg/d). In the dose expansion, pre- and postmenopausal pts (≤1 line of any prior therapy for ABC) received RIB (at the recommended Phase II dose [RP2D]) + LET (2.5 mg/d), FUL (500 mg, d1 and 15 of Cycle 1, then every 28 d), or TAM (20 mg/d) + goserelin (3.6 mg every 28 d; premenopausal pts only). Primary objectives: dose escalation = maximum tolerated dose (MTD) and/or RP2D of RIB + LET; dose expansion = safety of RIB (at the RP2D) + ET. Secondary objectives: antitumor activity, pharmacokinetics.


As of Mar 2, 2018, 59 Japanese pts out of 88 Asian pts were enrolled into 4 cohorts (Table). Two dose-limiting toxicities occurred (RIB 400 mg; increased aspartate aminotransferase [n = 1]; increased blood creatinine [n = 1]); MTD = RIB 400 mg + LET; RP2D = RIB 300 mg + LET. Median duration of RIB exposure was higher in the LET vs TAM/FUL cohorts (Table). See table for all-causality Grade 3/4 adverse events ≥10% (in any cohort). New Fridericia’s corrected QT interval (QTcF) >480 ms occurred in 0/5, 2/22, 2/15, and 0/16 pts in the RIB 400 mg + LET, RIB 300 mg + LET, RIB 300 mg + TAM, and RIB 300 mg + FUL cohorts; no QTcF >500 ms occurred. Preliminary efficacy was observed in all cohorts (Table). At steady state, RIB was rapidly absorbed in all cohorts; RIB 300 mg exposure was comparable between the LET and FUL cohorts and lower in the TAM cohort (Table).Table: 42P

RIB 400 mg + LET 2.5 mg (escalation)RIB 300 mg + LET 2.5 mg (escalation/expansion)RIB 300 mg + TAM 20 mg (expansion)RIB 300 mg + FUL 500 mg (expansion)
Enrolled, n67/151516
Median duration offollow-up, months21.613.812.910.1
Treatment ongoing, n (%)1 (16.7)14 (63.6)8 (53.3)7 (43.8)
Primary reason for discontinuation, n (%)
Disease progression5 (83.3)6 (27.3)4 (26.7)9 (56.3)
Median duration of exposure to RIB, months (range)19.1 (0–34)14.2 (0–27)12.5 (0–17)10.2 (1–16)
Most common (≥10% in any cohort) all-causality Grade 3/4 adverse events, n (%)
Neutropenia5 (83.3)13 (59.1)6 (40.0)9 (56.3)
Leukopenia2 (33.3)3 (13.6)2 (13.3)3 (18.8)
Increased ALT2 (33.3)2 (9.1)4 (26.7)3 (18.8)
Increased AST1 (16.7)01 (6.7)0
Increased lipase1 (16.7)2 (9.1)1 (6.7)1 (6.3)
Abnormal hepatic function1 (16.7)1 (4.5)00
Preliminary efficacy data,* %
RIB pharmacokinetic parameters at Cycle 1 Day 21
Geo-mean Cmax (CV% geo-mean§), ng/ml [n]1150.0 (6.7) [3]804.0 (42.0) [11]428.0 (48.2) [7]708.0 (67.7) [10]
Median Tmax (range), h [n]2.03 (2.02–6.00) [3]3.92 (1.97–5.92) [11]3.98 (1.88–4.10) [7]2.99 (0.98–4.13) [10]
Geo-mean AUC0–24h (CV% geo-mean§), hr•ng/ml [n]14600 (25.3) [3]10600 (37.8) [11]5450 (42.9) [7]9060 (58.9) [10]

ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC0–24h, area under the plasma concentration-time curve from 0 to 24 hours; CBR, clinical benefit rate; Cmax, maximum concentration; CV, coefficient of variation; geo-mean, geometric mean;

ORR, overall response rate; Tmax, time to reach Cmax.


Pts with measurable disease (n = 54).

ORR = complete response + partial response.

CBR = complete response + partial response + (stable disease + non-complete response/non-progressive disease ≥24 weeks).


CV% geo-mean = sqrt (exp [variance for log transformed data] – 1)*100.


In Japanese pts with HR+, HER2– ABC, the MTD of RIB was 400 mg and the RP2D was 300 mg. Preliminary safety and efficacy data are consistent with observations in non-Japanese pts.

Editorial acknowledgement

Editorial assistance was provided by Claire Wilson PhD of ArticulateScience Ltd.

Clinical trial identification


Legal entity responsible for the study

Novartis Pharmaceutical Corporation.


Novartis Pharmaceutical Corporation.


N. Masuda: Personal fees: Chugai, AstraZeneca, Pfizer, Kyowa-Kirin, Eisai, Takeda and Eli-Lilly, outside the submitted work. S. Noguchi: Grants: Novartis, AstraZeneca, Chugai; Other: Eisai, Takeda, Daiichi-Sankyo; Grants: Sysmex; Other: Kyowa Kirin, Fuji Film; Grants: Pfizer, outside the submitted work. S.J. Kim: Personal fees: Novartis, outside the submitted work. T. Toyama: Grants: Novartis Pharma, Eisai Co, Ltd, Chugai Pharmaceutical Co, Ltd, Nippon Kayaku Co, Ltd, Pfizer Japan Inc, Kyowa Hakko Kirin Co, Ltd, Taiho Pharma, Daiichi Sankyo Co, Ltd, Takeda Pharmaceutical Co, Ltd. T. Saeki: AstraZeneca, Eisai, Ono, Kyowa Hakko Kirin Taiho, Chugai, Nippon Kayaku, Hamamatsu photonics, Novartis, Global Software. T. Yamanaka: Personal fees: Novartis, Chugai, Pfizer, Taiho, outside the submitted work. J. Watanabe: Personal fees: Novartis Pharma, outside the submitted work. S. Nakamura: Research Funding AstraZeneca, Chugai Pharmaceutical Co., Daiichi Sankyo Co., Eisai Co., Ltd., Kyowa Hakko Kirin, Novartis Pharma KK, Pfizer Japan Inc., Taiho Pharmaceutical, Takeda Pharmaceutical Co; Personal fee (honoraria): AstraZeneca, Chugai Pharmaceutical Co., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Novartis Pharma KK, Pfizer Japan Inc., Taiho Pharmaceutical, Takeda Pharmaceutical Co. K. Inoue: Novartis, Pfizer, Chugai, DaiichiSankyo, Parexel / Puma Biotechnology, MSD, Bayer, Lilly, Esai. I. Gounaris: Employment: Novartis. Y. Han: Employee, stockholder: Novartis. T.S. Samant, M. Gazdoiu: Employee: Novartis. Y. Ito: Grants: Daiichi Sankyo, Chugai, Novartis, Parexel, EPS, MSD, AstraZeneca, Lilly, Kyowa Hakko Kirin, Covance, Taiho, A2 Healthcare. All other authors have declared no conflicts of interest.

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