Displaying One Session

Hall 405 Proffered Paper session
Date
19.11.2017
Session Time
08:30 - 10:45
Session Room
Hall 405
Chairs
  • F. Cardoso
  • Y. Lu
Breast cancer, early Proffered paper session 3 Proffered Paper session

57O - A nomogram for predicting the likelihood of axillary lymph node metastasis in breast cancer patients based on ultrasonographic-pathologic features (ID 2015)

Presentation Number
57O
Presentation Topic
Breast cancer, early
Lecture Time
08:30 - 08:42
Speakers
  • J. Lai
Authors
  • J. Lai
  • K. Chen
  • Y. Li
  • Z. Pan
  • S. Shen
  • Y. Yang
  • R. Gu
  • F. Liu
  • Y. Hu
  • X. Jiang
  • F. Yu
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

Axillary lymph node status is an important prognostic factor of breast cancer patients. Several variables have been confirmed as predictors of axillary lymph node metastasis in breast cancer. However, it is rather difficult to apply the nomogram for predicting the likelihood of axillary lymph node metastasis before surgery. This study aimed to construct a novel nomogram to predict the risk of axillary metastasis preoperatively in breast cancer patients based on ultrasonographic-pathologic features.

Methods

Data were collected from 1,273 patients who were histologically proven breast cancer between January 2012 and March 2017, and divided them into the training set and the validation set. Besides, the prospective validation study was registered at Clinicaltrials.gov. Statistically significant independent predictors were identified in multivariate logistic regression analysis. A receiver operating characteristic curve was implemented to evaluate the discriminative ability of the nomogram. Furthermore, a calibration plot was executed to compare actual versus predicted probability. Finally, decision curve analysis was used to assess the clinical usefulness of the nomogram.

Results

Based on the multivariate logistic regression analysis, axillary lymph node status was associated markedly with clinical tumor size, histological grade, longitudinal diameter, cortical thickness and hilum status. The area under the receiver operating characteristic curve was 0.876(95% confidence interval[CI]=0.830-0.923) in the validation set as compared to 0.873(95% confidence interval[CI]=0.851-0.896) in the training set. The predictive model was well-calibrated in the patient population. The decision curve suggested the clinical usefulness of our nomogram.

Conclusions

We have constructed a user-friendly tool that utilizes variables preoperatively available to clinicians and accurately predict the risk of axillary lymph node metastasis for individual patients based on ultrasonographic-pathologic features.

Clinical trial identification

The prospective validation study was registered at Clinicaltrials.gov (NCT02992769).

Legal entity responsible for the study

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Collapse
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

91O_PR - Analysis of the gaps on metastatic breast cancer policies and advocacy efforts to support policy development across the patient journey in Asia (ID 1668)

Presentation Number
91O_PR
Presentation Topic
Breast cancer, metastatic
Lecture Time
08:42 - 08:54
Speakers
  • K. Hunt
Authors
  • K. Hunt
  • F. Cardoso
  • M. Thrift-Perry
  • A. Cabanes
  • T. Cruz
  • K. Faircloth
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

In Asia, efficient metastatic breast cancer (mBC) diagnosis, treatment and care is hindered by cultural beliefs and the stigmatization of breast cancer (BC). Despite increasing recognition and efforts from policymakers, advocacy groups and the wider healthcare community, there is urgent need for targeted action and stakeholder collaboration to improve patient outcomes.

Methods

A comprehensive analysis of National Cancer Control Plans (NCCPs), policies and programs was conducted in Japan and South Korea, two developed Asian healthcare systems. Policy components were aligned to the BC/mBC patient journey, and evaluated using standardized criteria on adoption of NCCP goals, and BC/mBC policies and programs. Advocacy initiatives were identified in the policy analysis in Japan and South Korea and through an advocacy promising practice implemented in China.

Results

There has been considerable BC/mBC policy development in Asia but gaps persist across all areas of the patient journey. The analysis finds that cultural beliefs act as barriers to diagnosis and treatment, and deter policy development. For instance, BC/mBC stigmatization is not efficiently tackled due to low levels of trained primary care healthcare professionals (HCPs). This deficiency is also reflected in limited patient awareness and disease prevention, inefficient care coordination, disproportionate emphasis on surgery versus treatment, and use of complementary and alternative medicines. Similarly, access to palliative care and rehabilitative support remain important prevalent needs. Advocacy efforts identified in Japan, South Korea and China sought to fill policy gaps. In China, a model aimed at strengthening primary HCPs through a culturally-adapted BC education toolkit showed promising results for replication in other settings.

Conclusions

Engaging with stakeholders across the patient journey is critical to address cultural barriers and unmet needs of BC/mBC patients. Policy initiatives and promising practices in this research exemplify successful multi-stakeholder engagement to inform further advocacy and policy development.

Legal entity responsible for the study

Susan G. Komen; Pfizer, Inc.

Funding

Pfizer, Inc.

Disclosure

F. Cardoso: Consultant: Astellas/Medivation AstraZeneca Celgene Daiichi-Sankyo Eisai GE Oncology Genentech GlaxoSmithKline (GSK) Macrogenics Merck-Sharp Merus BV Mylan Novartis Pfizer Pierre-Fabre Roche Sanofi Teva. M. Thrift-Perry, K. Faircloth: Pfizer, Inc. All other authors have declared no conflicts of interest.

Collapse
Breast Cancer Proffered paper session 3 Proffered Paper session

Invited Discussant 57O and 91O (ID 2158)

Presentation Topic
Breast Cancer
Lecture Time
08:54 - 09:09
Speakers
  • J. Cortes Castan
Authors
  • J. Cortes Castan
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

92O - Everolimus (EVE) + letrozole (LET) in Asian patients with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Results of a subgroup analysis from the BOLERO-4 study (ID 1008)

Presentation Number
92O
Presentation Topic
Breast cancer, metastatic
Lecture Time
09:09 - 09:21
Speakers
  • T. Toyama
Authors
  • T. Toyama
  • J. Jeong
  • V. Srimuninnimit
  • V. Sriuranpong
  • W. Noh
  • K. Tsugawa
  • M. Takahashi
  • H. Iwase
  • C. Arce
  • A. Ridolfi
  • C. Lin
  • M. Royce
  • F. Cardoso
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

Results from the primary analysis of the open-label, single-arm, phase 2 study BOLERO-4 demonstrated that first-line (1L) EVE + LET was an effective combination with a manageable safety profile in postmenopausal patients with ER+ HER2− ABC. Here, we present results from a predefined subgroup analysis of 1L progression-free survival (PFS) and safety by race (Asian versus non-Asian).

Methods

Patients received EVE 10 mg/day + LET 2.5 mg/day until disease progression, unacceptable toxicity, or withdrawal of consent. 1L PFS per local investigator assessment was analyzed overall on the full analysis set (FAS; primary endpoint) and by patient subgroup. This study was not designed to use the SWISH protocol for prevention for stomatitis.

Results

At the data cutoff (December 17, 2016), 44 Asian and 158 non-Asian (Caucasian 72%; Black 4%; Pacific Islander <1%; other 2%) patients had a median PFS and 18- and 24-month KM estimated PFS rates similar to the FAS (Table). In general, all grade adverse events (AEs), regardless of causality or severity, were more common among Asian patients versus non-Asians and the overall population, particularly for stomatitis, weight decreased, anemia, hyperglycemia, decreased appetite, rash and nasopharyngitis. AEs were mostly grade 1–2 in severity and anemia was the most common grade 3–4 AE among both Asian (20%) and non-Asian (8%) patients.

FASRACE
N = 202Asian (n = 44)Non-Asian (n = 158)
No. of PFS events, n (%)108 (53.5)26 (59.1)82 (51.9)
Median PFS (95% CI), months22.0 (18.1–25.1)20.3 (14.8–26.0)22.0 (17.1–25.7)
KM estimated PFS rate (95% CI), %
18-months58.8 (50.9–65.8)65.8 (49.1–78.1)56.7 (47.5–64.8)
24-months42.9 (35.0–50.5)44.0 (28.0–58.8)42.8 (33.7–51.5)
CI, confidence interval; KM, Kaplan-Meier

Conclusions

Results from this predefined subgroup analysis were consistent with previously reported BOLERO-4 data, showing that 1L EVE + LET offers clinical benefits irrespective of patient race, with no new safety signals reported. Although some AEs were more common among Asian patients versus non-Asians and the overall population, they were mostly grade 1–2 in severity.

Clinical trial identification

NCT01698918 EudraCT Number (EU number) 2012-003065-17

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

T. Toyama: Research funding from Eisai, Chugai, Novartis, Nippon Kayaku, Kyowa Hakko Kirin, Daiichi-Sankyo, Takeda, J. Jeong: Research funding from Dong-A, Boryung, LG Life Sciences, Antigen; Honoraria from Roche, Alvogen, Novartis, Pfizer, Covidien, V. Sriuranpong: Honoraria from Novartis, Roche, MSD, Sanofi, Eisai, AstraZeneca, H. Iwase: Research funding from AstraZeneca, Chugai-Roche, Taiho, Daiichi-Sankyo, Novartis, Pfizer, Kyowa Hakko-Kirin, Eisai; Honoraria from AstraZeneca, Novartis, Takeda, Chugai-Roche. C. Arce: Novartis employee, A. Ridolfi: Novartis Pharma SAS employee, C. Lin: Novartis employee and stocks, M. Royce: Research funding from Novartis; Consultant for Celltrion, BCI; Honoraria from Novartis, Syndax, F. Cardoso: Research funding for clinical trials by institution; consultant for Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GSK, MacroGenics, Merck, Merus BV, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Teva

All other authors have declared no conflicts of interest.

Collapse
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

93O - Phase 2 study of pembrolizumab for metastatic triple-negative breast cancer (mTNBC): Japanese subgroup results of KEYNOTE 086 (ID 1352)

Presentation Number
93O
Presentation Topic
Breast cancer, metastatic
Lecture Time
09:21 - 09:33
Speakers
  • M. Hattori
Authors
  • M. Hattori
  • K. Tamura
  • H. Mukai
  • Y. Miyoshi
  • N. Masuda
  • E. Suzuki
  • H. Ishiguro
  • S. Ohtani
  • F. Hara
  • T. Shimamoto
  • K. Yamamoto
  • Y. Ding
  • G. Aktan
  • V. Karantza
  • H. Iwata
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

As treatment outcomes for mTNBC are poor, new treatment options are needed. We present a subgroup analysis for the safety and antitumor activity of pembrolizumab (PEM) as a therapy for Japanese patients (pts) with mTNBC in Cohorts A and B of KEYNOTE 086.

Methods

Pts with centrally confirmed mTNBC, at least one systemic treatment (Cohort A) or no prior systemic therapy (Cohort B) for metastatic disease, ECOG PS 0-1, and regardless of tumor PD-L1 expression (Cohort A) or with a tumor PD-L1 combined positive score (CPS) ≥1% (Cohort B), received PEM 200 mg IV every 3 weeks (wk) for 24 months (m) or until disease progression, intolerable toxicity, or investigator or patient (pt) decision. Tumor imaging was performed Q9W for 12 m and Q12W thereafter. Clinically stable pts with PD could remain on PEM until PD was confirmed on subsequent assessment. Primary endpoints were ORR (RECIST, central review) in Cohort A and safety in Cohorts A and B. Secondary were ORR in Cohort B, disease control rate (CR + PR + SD ≥ 24 wk), PFS and OS in Cohorts A and B.

Results

Of 20 pts in Cohort A, 12 had PD-L1 (+) tumors and 8 had PD-L1 (-) tumors. The median age was 53.5 y, 11 pts had elevated LDH and 13 pts had visceral metastases. Of 9 pts in Cohort B, median age was 38.0 y, 1 pt had elevated LDH, 5 pts had visceral metastases. As of Nov 10, 2016, the best overall response was PR in 1 pt and SD in 2 pts in Cohort A, and CR in 1 pt and SD in 2 pts in Cohort B. Median PFS was 2.0 m (95% CI, 1.7 – 2.1) in Cohort A, and 2.1 m (95% CI, 1.6 – 4.2) in Cohort B. Median OS was 8.3 m (95% CI, 4.6 – 10.3) in Cohort A, and was not reached in Cohort B. Drug-related AEs (DRAEs) occurred in 20 pts (67.0%) in Cohorts A and B; the most common DRAEs were pruritus (4 pts), fatigue, pyrexia, anemia, rash, and diarrhea (3 pts each). Grade (Gr) 3-4 DRAEs were diarrhea, nausea, and bacteraemia (1 pt each), all in Cohort A. Infusion reaction (1 pt, Gr 2), interstitial lung disease (1 pt, Gr 1), hypersensitivity (1 pt, Gr 2) and hyperthyroidism (1 pt, Gr 1) were seen as irAE. No pts died or discontinued PEM due to AEs.

Conclusions

Data from 29 Japanese pts in Cohorts A and B suggest that PEM monotherapy has a well tolerated safety profile and anti-tumor activity which are similar to those reported in the overall populations.

Clinical trial identification

NCT02447003.

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ, USA

Funding

Merck & Co., Inc., Kenilworth, NJ, USA

Disclosure

H. Mukai: Received personal fees as honoraria from AstraZeneca, Novartis Pharma, Daiichi Sankyo, and Taiho Pharmaceutical, and received research funds from Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and MSD.K.K. N. Masuda: Honoraria: Chugai, Astrazeneca. H. Ishiguro: Advisory board: MSD.K.K. T. Shimamoto, K. Yamamoto: Employees of MSD.K.K. Y. Ding, G. Aktan, V. Karantza: Employees of Merck

All other authors have declared no conflicts of interest.

Collapse
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

94O - Phase Ib study of ribociclib (RIB) + letrozole (LET) in a subset of Asian patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) (ID 1377)

Presentation Number
94O
Presentation Topic
Breast cancer, metastatic
Lecture Time
09:33 - 09:45
Speakers
  • Y. Yap
Authors
  • Y. Yap
  • Y. Ito
  • O. Bornstein
  • Y. Han
  • T. Samant
  • X. Liu
  • J. Chiu
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

MONALEESASIA is an ongoing Phase Ib dose-escalation/-expansion study evaluating RIB + LET in a subset of Asian pts from Hong Kong and Singapore with HR+, HER2–ABC.

Methods

Postmenopausal pts from Hong Kong and Singapore with HR+, HER2– ABC and no prior systemic therapy for ABC received RIB (400 or 600 mg/day; 3-weeks-on/1-week-off) + LET (2.5 mg/day; continuous). Dose escalation used a Bayesian Logistic Regression Model with overdose control. The primary endpoint was to determine the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D); secondary endpoints included safety and pharmacokinetic (PK) profile. Blood samples for PK non-compartmental analysis were collected on Days 1 and 21 of Cycle 1 from pre-dose to 24 h post-dose.

Results

At data cut-off (Jan 16, 2017), 26 pts were enrolled (RIB 400 mg: n = 6; 600 mg: n = 20). One dose-limiting toxicity was observed at 600 mg (Grade 3 increased alanine transaminase [ALT]); the MTD/RP2D was RIB 600 mg/day (3-weeks-on/1-week-off) + LET 2.5 mg/day (continuous). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 4/6 pts at 400 mg and 17/20 pts at 600 mg during the dose-escalation and -expansion parts. The most common Grade 3/4 TRAEs (≥20% in either cohort; 400 mg vs 600 mg) were decreased neutrophil count (n = 3 vs n = 7), neutropenia (n = 1 vs n = 6), increased ALT (n = 1 vs n = 4), and increased aspartate transaminase (n = 0 vs n = 4). After a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21), absorption of both RIB and LET was rapid (Table); increases in RIB exposure were dose dependent.

Conclusions

The MTD/RP2D was declared as RIB 600 mg/day (3-weeks-on/1-week-off) + LET 2.5 mg/day (continuous) in Asian pts from Hong Kong and Singapore with HR+, HER2– ABC. Preliminary safety and PK data are consistent with prior observations in non-Asian pts.

Clinical trial identification

CLEE011A2115C/NCT02333370.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

Y-S. Yap: Received honoraria and provided consultancy for Novartis. Y. Ito: Yoshinori Ito reports grants from MSD, AstraZeneca, Novartis, Parexel, Chugai, and Lilly. O. Bornstein: Orna Bornstein is an employee of Novartis Pharmaceuticals Corporation. Y. Han: Yu Han is an employee at Novartis Pharmaceuticals Corporation. T. Samant: Tanay Samant is an employee of Novartis Pharmaceuticals Corporation and owns stocks/shares in Novartis Pharmaceuticals Corporation. X. Liu: Xiaochun Liu is an employee of Novartis Pharmaceuticals Corporation and owns stocks in Novartis Pharmaceuticals Corporation. J. Chiu: Dr. Chiu served on advisory boards for Novartis and Pfizer.

Summary of RIB and LET PK profiles

RIB
LET
DayDose level (mg)
Geo-mean Cmax (CV % geo-mean), ng/ml[n]Median Tmax (range), h[n]Geo-mean AUC0–24h (CV % geo-mean), h*ng/ml[n]Geo-mean T1/2, acc(CV % geo-mean), h[n]Geo-mean Cmax(CV % geo-mean), ng/ml[n]Median Tmax (range), h[n]Geo-mean AUC0–24hCV % geo-mean), h*ng/ml[n]Geo-mean T1/2, acc(CV % geo-mean), h[n]
RIBLET
Cycle 1 Day 1400 (n = 6)2.5802.0 (27.7) [6]1.02 (0.50–4.00) [6]7540.0 (25.2) [6]Not reported30.0 (30.4) [6]2.02 (0.50–4.03) [6]479.0 (13.0) [6]Not reported
600 (n = 20)2.51120.0 (45.5) [20]2.15 (1.00–6.08) [20]12,100.0 (39.5) [20]Not reported38.5 (82.8) [20]2.00 (0.50–8.05) [20]629.0 (96.7) [20]Not reported
Cycle 1 Day 21400 (n = 6)2.51390.0 (0.5) [2]1.50 (1.00–2.00) [2]15,400.0 (31.1) [2]25.1 (10.6) [2]170.0 (21.4) [2]1.00 (1.00–1.00) [2]3320.0 (28.0) [2]97.9 (25.2) [2]
600 (n = 20)2.51620.0 (15.0) [6]2.26 (2.00–4.00) [6]21,500.0 (21.0) [6]22.9 (34.8) [6]117.0 (31.0) [11]1.00 (0.50–7.88) [11]2330.0 (33.0) [11]50.6 (105.4) [11]

AUC, area under the plasma concentration-time curve; Cmax, maximum concentration;

CV % geo-mean = sqrt (exp [variance for log transformed data] – 1)*100; CV, coefficient of variation; exp, experiment;

geo-mean, geometric mean; sqrt, square root; T1/2, acc, effective accumulation half-life; T1/2, elimination half-life;

Tmax, time to reach Cmax

Collapse
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

Invited Discussant 92O, 93O and 94O (ID 2159)

Presentation Topic
Breast cancer, metastatic
Lecture Time
09:45 - 10:00
Speakers
  • Y. Lu
Authors
  • Y. Lu
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

95O - Efficacy and safety of palbociclib plus endocrine therapy in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the Asia-Pacific region: Data from PALOMA-2 and -3 (ID 1649)

Presentation Number
95O
Presentation Topic
Breast cancer, metastatic
Lecture Time
10:00 - 10:12
Speakers
  • S. Im
Authors
  • S. Im
  • N. Masuda
  • Y. Im
  • K. Inoue
  • S. Kim
  • A. Redfern
  • J. Lombard
  • D. Lu
  • K. Puyana Theall
  • E. Gauthier
  • H. Mukai
  • J. Ro
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

The efficacy and tolerability of palbociclib (P) + endocrine therapy (ET) in ABC patients (pts) was previously established; here, we report results in the Asia-Pacific (AP) region (Australia, Japan, Korea, Taiwan).

Methods

In PALOMA-2, postmenopausal women untreated for their HR+/HER2- ABC were randomized 2:1 to P (125 mg/d [3/1 schedule]) + letrozole (L; 2.5 mg/d) or placebo (PB)+L. In PALOMA-3, women of any menopausal status with HR+/HER2- ABC, whose disease had progressed after previous ET, were randomized 2:1 to P + fulvestrant (F; 500 mg) or PB+F.

Results

Of 666 PALOMA-2 pts, 92 (14%) were from the AP region (P+L, 64; PB+L, 28). Baseline characteristics: median age (61 y) younger than overall population; white (20%), Asian (79%); ≥2 disease sites (70%); visceral disease (59%); prior (neo)adjuvant ET (64%); disease-free interval >12 months since prior (neo)adjuvant therapy (58%). Median PFS (mPFS): 22 mo (95% CI, 19-26) for P+L vs 14 mo (7-22) for PB+L (HR, 0.49; 1-sided P=0.007). All-grade treatment-emergent adverse events (TEAEs) (P+L/PB+L) occurred in 100%/96% of pts; the most common AE in the P+L arm was neutropenia (91%). 55% of P+L pts required a dose reduction due to AEs. Of 521 PALOMA-3 pts, 114 (22%) were from the AP region (P+F, 78; PB+F, 36). Baseline characteristics: younger (median age 53 y) and more premenopausal pts (38%) vs overall population; white (23%), Asian (75%); ≥2 disease sites (66%); visceral disease (57%); prior ET (100%); prior chemotherapy for ABC (70%). mPFS: 13 mo (95% CI, 9-16) for P+F vs 6 (4-9) for PB+F (HR, 0.51; 1-sided P=0.002). All-grade TEAEs (P+F/PB+F) occurred in 100%/92% of pts; the most common AE in the P+F arm was neutropenia (95%). 51% of P+F pts required a dose reduction due to AEs.

Conclusions

Because PALOMA-2 only enrolled postmenopausal pts and percentages of premenopausal pts in AP vs other regions was higher, the proportion of AP pts was higher in PALOMA-3 vs -2. P+ET showed clinically meaningful improvement in mPFS vs PB+ET and a tolerable safety profile in AP pts with HR+/HER2- ABC in the 1st-line and later-lines of therapy, regardless of menopausal status.

Clinical trial identification

Pfizer (NCT01740427; NCT01942135).

Legal entity responsible for the study

Pfizer Inc

Funding

Pfizer Inc.

Disclosure

S-A. Im: Consulting or advisory role for AstraZeneca, Novartis, Hanmi Corp, and Spectrum, N. Masuda: Honoraria from Chugai and AstraZeneca, K. Inoue: Research funding from Pfizer, Lilly, Chugai, Daiichi-Sankyo, Taiho, MSD, Parexel (Puma), S-B. Kim: Research funding from Novartis, Sanofi-Aventis, Kyowa-Kirin Inc, and Dongkook Pharma Co., Ltd. A. Redfern: Advisory board for Pfizer Australia, J. Lombard: Honoraria from Roche and AstraZeneca, D. Lu, K. Puyana Theall, E.G. Gauthier: Employee and owns stock in Pfizer, H. Mukai: Honoraria from AstraZeneca, Eisai, Novartis Pharma and Taiho Pharmaceutical, and received research funds from Chugai Pharmaceutical, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and Sanofi

All other authors have declared no conflicts of interest.

Collapse
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

96O - MONARCH 2: Abemaciclib in combination with fulvestrant in Asian women with HR+, HER2- advanced breast cancer who progressed on endocrine therapy (ID 1808)

Presentation Number
96O
Presentation Topic
Breast cancer, metastatic
Lecture Time
10:12 - 10:24
Speakers
  • M. Toi
Authors
  • M. Toi
  • C. Huang
  • Y. Im
  • H. Iwata
  • J. Sohn
  • H. Wang
  • N. Masuda
  • Y. Lin
  • S. Sakaguchi
  • N. Bourayou
  • A. Llombart
  • G. Sledge
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45

Abstract

Background

MONARCH 2 demonstrated that the addition of abemaciclib, a CDK4 & 6 inhibitor dosed on a continuous schedule, to fulvestrant (F) significantly improved progression-free survival (PFS) and objective response rate (ORR) compared to placebo (P) plus F (PFS hazard ratio [HR], 0.553, P<.0000001; ORR in measurable disease 48.1% vs 21.3%, P<.001) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who had progressed on endocrine therapy (ET).

Methods

MONARCH 2 is a Phase 3 double-blind trial of abemaciclib + F vs P + F in women with HR+, HER2- advanced breast cancer. Women who progressed on (neo)adjuvant endocrine therapy (ET), ≤12 m from end of adjuvant ET, or on first line ET for MBC and who had not received chemotherapy for metastatic disease were eligible; pre/perimenopausal pts received a gonadotropin-releasing hormone agonist. Pts were randomized 2:1 to receive abemaciclib at 150 mg Q12H (or 200 mg prior to amendment) or P plus F (500 mg, per label) and stratified by metastatic site (visceral, bone only, or other) and resistance to prior ET (primary vs secondary). We present the primary objective of investigator-assessed progression-free survival (PFS), and secondary efficacy and safety endpoints in Asian pts.

Results

214 Asian pts were randomized to abemaciclib plus F (N = 149) and to P plus F (N = 65). In the ITT population, 122 PFS events were observed with a median PFS of 22.8 m for abemaciclib plus F and 11.6 m for P + F (HR: 0.515; 95% CI: 0.359, 0.740, P<.001 by log-rank test). In pts with measurable disease (n = 170, 79.4%), the ORR was significantly higher in abemaciclib plus F 48% (2.4% complete response [CR]) vs 23.4% (0% CR) for P plus F, P=.004. The most frequent adverse events for abemaciclib plus F vs P plus F were diarrhea (90.5% vs 20.0%), neutropenia (68.2% vs 4.6%), nausea (37.8% vs 16.9%), and fatigue (53.8% vs 30.9%).

Conclusions

Abemaciclib + F was an effective treatment in Asian pts with HR+, HER2- advanced breast cancer who progressed on endocrine therapy with significantly improved PFS and ORR. These findings were consistent with the intent-to-treat population in MONARCH 2.

Clinical trial identification

NCT02107703.

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

H. Iwata: Honoraria: Chugai Pharmaceutical, Eisai, AstraZeneca, Novartis, Daiichi Sankyo, Taiho Pharmaceutical. Research funding: GSK, Daiichi Sankyo, Chugai Pharmaceutical, Nippon Kayaku, Novartis, Pfizer, AstraZeneca, Eisai, Eli Lilly, and MSD. J.H. Sohn: Research Funding: AstraZeneca, Eli Lilly, Novartis, Genentech, Pfizer, MSD Oncology, N. Masuda: Honoraria: Chugai Pharma, AstraZeneca Research Funding: Chugai Pharma (Inst), AstraZeneca (Inst), Kyowa-Kirin (Inst), MSD Oncology (Inst), Novartis (Inst), Pfizer (Inst), Eli Lilly (Inst), Y. Lin, S. Sakaguchi, N. Bourayou: Employee of Eli Lilly and Company, A. Llombart: Honoraria: Roche, Novartis, Pfizer Consulting or Advisory Role: Roche, AstraZeneca, Eli Lilly Research Funding: Pfizer, Roche, G. Sledge: Leadership: Syndax Stock or Other Ownership: Syndax Honoraria: Symphogen Consulting or Advisory Role: Symphogen, Coherus Biosciences, Radius Health, Peregrine Pharmaceuticals, Taiho Pharmaceutical Research Funding: Roche (Inst)

All other authors have declared no conflicts of interest.

Collapse
Breast cancer, metastatic Proffered paper session 3 Proffered Paper session

Invited Discussant 95O and 96O (ID 2160)

Presentation Topic
Breast cancer, metastatic
Lecture Time
10:24 - 10:39
Speakers
  • J. Tsang
Authors
  • J. Tsang
Session Room
Hall 405, Singapore, Singapore, Singapore
Date
19.11.2017
Session Time
08:30 - 10:45