ESMO Supporter 2018

Displaying One Session

ICM - Room 1 Poster Discussion session
Date
21.10.2018
Time
09:15 - 10:30
Location
ICM - Room 1
Chairs
  • Lisa Carey (Chapel Hill, US)
  • Alessandra Gennari (Novara, IT)
  • Caroline Schroeder (Groningen, NL)
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Session DOI

Lecture Time
09:15 - 09:15
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

293PD_PR - Ribociclib (RIBO) + letrozole (LET) in male patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) and no prior endocrine therapy (ET) for ABC: Preliminary subgroup results from the phase 3b CompLEEment-1 trial

Presentation Number
293PD_PR
Lecture Time
09:15 - 09:15
Speakers
  • Claudio Zamagni (Bologna, IT)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

CDK4/6 inhibitor RIBO is approved for use in combination with an aromatase inhibitor for the treatment of HR+, HER2– ABC in postmenopausal women with no prior therapy for ABC, based on the significantly prolonged progression-free survival versus placebo + LET observed in the pivotal phase 3 MONALEESA-2 trial (Hortobagyi et al. NEJM 2016). However, relatively rare pt subsets such as men with HR+, HER2– ABC were not included in that trial. Here, we report early safety results for men enrolled in CompLEEment-1, an open-label, phase 3b trial evaluating RIBO+LET as first-line therapy in an expanded pt population.

Methods

Pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy, and no prior ET for ABC received RIBO (600 mg/day, 3 wk on/1 wk off) + LET (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6-mg subcutaneous implant every 28 days). The primary outcome was safety and tolerability. A pre-planned interim analysis was conducted ~15 months after first pt first visit.

Results

Of the first 1,008 pts enrolled who completed 56 days of follow-up or discontinued before the data cut-off, 20 were men. Median age was 63.5 years and all had an Eastern Cooperative Oncology Group performance status ≤1; 45.0% had stage IV disease at diagnosis. The most common sites of metastasis were lung (75.0%), lymph nodes (40.0%), and liver (20.0%). The most frequent adverse events (AEs) were hot flush (30.0%), neutropenia (20.0%), and constipation (20.0%). Grade ≥3 AEs included neutropenia (4 pts, 20.0%), increased alanine aminotransferase (2 pts, 10.0%), and increased aspartate aminotransferase (1 pt, 5.0%). QT prolongation was infrequent, occurring in 3 (15.0%) men; all events were grade 1/2. Dose reduction or interruption due to AEs occurred in 35.0% of men; 2 discontinued treatment due to AEs.

Conclusions

Preliminary results from the CompLEEment-1 study demonstrate the safety and tolerability of first-line RIBO+LET+goserelin in male pts, consistent with previous reports in female pts. NCT02941926.

Clinical trial identification

NCT02941926

Editorial Acknowledgement

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Holly C. Cappelli, PhD, ProEd Communications, Inc., for her medical editorial assistance with this abstract.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

294PD_PR - Management and outcome of metastatic breast cancer in men in the national multicenter observational ESME program

Presentation Number
294PD_PR
Lecture Time
09:15 - 09:15
Speakers
  • Junien Sirieix (Tours, FR)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

Breast Cancer (BC) in men accounts for 1% of all BC. Management is still based largely on BC management in women. Only small and selected retrospective series on metastatic cases have been reported so far. Based on a national database, we aimed at providing a large comprehensive analysis of metastatic BC (MBC) in men.

Methods

ESME MBC platform is a French multi-center retrospective real life database using a clinical trial-like methodology to collect data from 18 French Comprehensive Cancer Centers. It includes data from each newly diagnosed MBC patients having initiated at least one treatment between 01/2008 and 12/2014. Cases occurring in men were retrieved and compared to the overall female population (characteristics, Student T-test), and to a population of women matched (1/1) on age, histology, grade, adjuvant treatment and metastasis location, regarding treatment effects and survival.

Results

Of 16 701 evaluable patients, 149 (0.89%) men were identified. Main comparative characteristics are listed below.

Men (n=149) Women (n=16552) p

Mean age (SD) (years)

Median age (range) (years)

68.1y (11.2)

69y (44-90)

60.6y (13.8)

61y (19-99)

<0.0001

.

Histological Subtypes :

- HR+/HER2-

- Triple Negative

- HER2+

- missing

105 (78.4%)

6 (4.5%)

23 (17.1%)

15

9815 (65.6%)

2315 (15.4%)

2840 (19%)

1582

p= 0.0019

p= 0.0005

p=0.62

.

Metastatic de novo 49 (32.9%) 4754 (28.7%) p=0.26

In HR+/HER2- men, 45/105 (42.9%) received frontline hormonal therapy : tamoxifen (20/45), aromatase inhibitor (AI) ± LHRH analogs (18/45), others (7/45). Median PFS was 9.8 months (m) without evidence of statistically difference between HT types. Compared with a matched cohort of women , median PFS was similar : 9.8m versus 13.0m (p=0.8). For HR+/HER2- men receiving front line CT (29/105 (27.6%)), median PFS was 6.9m and was similar to the 6.3m PFS in matched women (HR=1.24, [0.69-2.23]). The overall survival in men was 41.8m versus 34.9m in matched women (p=0.745).

Conclusions

We report on one of the largest series of MBC in men. Compared with women, prognosis and treatment effects look the same. More biological information is needed to improve the customized management of MBC in men.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

273PD_PR - Final analysis of the Male-GBG54 study: A prospective, randomised multi-centre phase II study evaluating endocrine treatment with either tamoxifen +/- gonadotropin releasing hormone analogue (GnRHa) or an aromatase inhibitor + GnRHa in male breast cancer patients

Presentation Number
273PD_PR
Lecture Time
09:15 - 09:15
Speakers
  • Mattea Reinisch (Essen, DE)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

Over 90% of mBC pts have hormone receptor positive disease. Until today tam is considered the standard of care. Due to the low incidence of mBC, there is a lack of data regarding its efficacy and safety. No prospectively randomized study in mBC pts has been completed so far. The Male-GBG54 study is the first prospective, randomized, multicenter trial evaluating the efficacy and safety of different endocrine treatment options in male pts with BC.

Methods

In the Male-GBG54 trial (NCT01638247), pts were randomized to receive tam 20mg/day per os (p.o.) in Arm A, tam + GnRHa subcutaneous (s.c.) q3m in Arm B and exemestane 25 mg/day p.o. + GnRHa s.c. in Arm C for 6 months (mo) as (neo)adjuvant or metastatic therapy. Further treatment was conducted as per local guidelines. Primary objective was the estradiol (E2) suppression after 3 mo. Secondary objectives were the E2 suppression after 6 mo and levels of different steroidal hormones after 3 and 6 mo. Quality of life was assessed using validated questionnaires. 14 pts/group were needed for the F-test to have 80% power to detect a difference in estradiol decrease between the groups at the 5% significance level.

Results

Between October 2012 and May 2017, 55 pts were randomized in Germany, of whom 46 pts were fully evaluable and comprised the 6-mo analysis set. The median age was 62 years. Baseline characteristics were well balanced between the 3 arms. The median E2 level with tam increased by 67% after 3 mo and by 41% after 6 mo. In pts receiving tam + GnRH and AI+ GnRH, there was an initial decrease of E2 after 3 mo of 85% and 73% respectively. After 6 mo of therapy the decrease was 59% and 63% respectively. Other hormone parameters will also be presented at the meeting.

Conclusions

This is worldwide the first fully recruited prospective randomized trial, evaluating the impact of 3 different endocrine treatments in male BC. The analysis revealed an increase of E2 levels along the course of therapy after an initial steep decrease when GnRHa was given. The therapy was well tolerated with no safety signals.

Clinical trial identification

Male-GBG54 trial (NCT01638247)

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Invited Discussant 293PD, 294PD and 273PD

Lecture Time
09:15 - 09:30
Speakers
  • Caroline Schroeder (Groningen, NL)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Q&A led by Discussant

Lecture Time
09:30 - 09:40
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

285PD - Balixafortide (a novel CXCR4 inhibitor) and Eribulin in HER2-neg Metastatic Breast Cancer (MBC) patients (pts): a Phase I trial

Presentation Number
285PD
Lecture Time
09:40 - 09:40
Speakers
  • Javier Cortes Castan (Barcelona, ES)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

CXCR4 is expressed in a variety of cancer types. The CXCR4/ SDF-1 axis plays a critical role in tumour growth, angiogenesis, metastasis and regulates function and trafficking of immune cells to the tumour microenvironment. CXCR4 antagonists enhance activity of different anti-cancer treatments in preclinical models. We assessed safety, tolerability and activity of the CXCR4 antagonist, balixafortide (B), in combination with eribulin (E) in heavily pre-treated MBC pts.

Methods

This Phase I, open-label trial enrolled HER2-negative, CXCR4-positive MBC patients previously treated with 1-3 chemotherapy (CT) regimens for MBC. A 3 + 3 dose escalation design was used, followed by an Expanded Cohort. All cohorts received E on days 2 and 9, and B on days 1-3, and 8-10 of 21-day cycles.

Results

Eleven cohorts were enrolled receiving B at 0.5-5.5 mg/kg. As no DLT was confirmed the MTD was not reached, so the highest B dose (5.5mg/kg) cohort was expanded to 24 pts. In the overall population, median age was 55.5 [33-82] years and median number of prior CT regimens for MBC was 2. TNBC pts were 13 (23%).Most common Gr 3-4 AEs were neutropenia (23 [41%]) and febrile neutropenia (6 [11%]). Two (3.6%) pts died due to septic shock and pneumonia. Anti-tumour activity is summarised in the table.

Efficacy populationa

Expanded CohortOverall Population
(n = 24)(n = 54)
Objective Response Rate, N (% [95% CI])9 (37·5% [18·8 − 59·4])16 (29·6% [18·0 − 43·6])
Clinical Benefit Rateb, N (% [95% CI])15 (62·5% [40·6 − 81·2])24 (44·4% [30·9 − 58·6])
Median Treatment Duration (weeks, range)25·9 (4·4-50·9)16·0 (1·4-72)

a. Patients who received at least one full cycle of study treatment. b. CR+PR+SD ≥6 months In the Expanded Cohort, median PFS was 6·2 [95% CI, 2·9–8·1] months and 1 year OS was 75% [95% CI, 53–88]. Mature OS data for the Overall Population and the Expanded Cohort will be presented.

Conclusions

This is the first trial to investigate a CXCR4 antagonist in MBC. The tolerability profile and promising anti-tumor activity observed with B + E in this Phase I study warrants further investigation as well as exploration of additional combinations of B with other anti-cancer therapies.

Clinical trial identification

NCT01837095.

Legal entity responsible for the study

Polyphor.

Funding

Polyphor.

Disclosure

J. Cortes Castan: Consultancy fees: Polyphor; Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer; Consulting Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, Merus. M. Martín: Grant: Novartis; Personal fees: Amgen, Roche, AstraZeneca, Pfizer. S. Pernas Simon: Consultancy and advisory board fees: AstraZeneca, Celgene, Roche. S. Lopez-Tarruella: Consultancy and advisory fees: Celgene, Pfizer, Novartis, AstraZeneca; Travel fees: Roche. L.M. Manso: Research funding: Tesaro. J.A. Perez Fidalgo: Travel fees: Roche, Pfizer, AstraZeneca; Speaker bureau: Roche, Pfizer, AstraZeneca, Ipsen, PharmaMar. C. Hernando: Immediate family member, stocks and employment: Celgene. F. Ademuyiwa: Research funding: Abbvie, Seattle Genetics, Nektar. I.A. Mayer: Advisory board honoraria: Novartis, AstraZeneca, Lilly; Research funding: Pfizer, Genentech. T. Pluard: Personal fees: Novartis, Pfizer, Genentech. M. Martinez Garcia: Consultancy fees: Roche, Celgene; Speaker's bureau: Roche, Pierre Fabre; Travel fees: Roche, Celgene. L.T. Vahdat: Research funding: OTS, Rexahn, Immunomedics, Pharmamar; Honoraria and consultancy fees: Celldex, Seattle Genetics; Speaker's bureau: Eisai. A. Wach, B. Romagnoli: Shareholder and employee: Polyphor. D. Barker: Shareholder: Polyphor and Novartis; Employee: Polyphor. P.A. Kaufman: Consultancy fees: Polyphor, Eisai, Roche/Genentech. All other authors have declared no conflicts of interest.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

286PD - Post-treatment biopsies show evidence of cell cycle arrest and immune cell infiltration into tumors of ladiratuzumab vedotin-treated advanced breast cancer patients

Presentation Number
286PD
Lecture Time
09:40 - 09:40
Speakers
  • Jennifer Specht (Seattle, US)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

Ladiratuzumab vedotin (LV) is a monomethyl auristatin E (MMAE)-conjugated IgG1 humanized antibody-drug conjugate (ADC) against LIV-1, a highly expressed transmembrane protein in breast cancer. A previously reported mechanism of action for LV is MMAE-driven microtubule inhibition, which results in mitotic arrest and cell death. We present data from an ongoing phase 1 study of LV monotherapy in women with unresectable, locally advanced, or metastatic breast cancer (NCT01969643), exploring the relationship between biomarkers of tumor cytotoxicity and the activation of the immune system in the tumor microenvironment (TME) of longitudinal biopsies. LV monotherapy was well tolerated in this study and showed encouraging clinical activity (Modi 2017).

Methods

We evaluated tumor biopsies pre- and ∼4 days post-tx. Up to 40 pairs of matched samples from hormone receptor-positive (HR+) and triple negative breast cancer (TNBC) pts were analyzed by both immunohistochemistry (IHC) and RNAseq, or by mass-spectroscopy (MS).

Results

The presence of macrophages and dendritic cells in baseline biopsies correlated with antitumor activity. Four days post-tx, MMAE levels were higher in tumor biopsies (∼10-fold increase) as measured by MS, compared to plasma. In post-tx biopsies, G2/M arrest and substantial acute changes within the TME were observed by IHC, including increased numbers of tumor infiltrating lymphocytes (TILs) in the stroma of HR+ and TNBC tumors and CD68+ macrophages in TNBC pts (∼2-fold; p < 0.06). Next generation sequencing identified increased expression of genes associated with cell cycle regulation (e.g., Cyclin B), immune response (e.g., CXCL10 and IFN-induced proteins), and confirmed signatures associated with macrophages and dendritic cells.

Conclusions

These data expand upon preclinical observations that MMAE-linked ADCs can induce mitotic arrest, immunomodulation, and immunogenic cell death. These translational data strongly support further clinical investigation of LV monotherapy and LV in combination with immuno-oncology agents, e.g. checkpoint inhibitors, as in the SGNLVA-002 study (NCT03310957).

Clinical trial identification

NCT01969643, first posted 25 October 2013.

Legal entity responsible for the study

Seattle Genetics.

Funding

Seattle Genetics.

Editorial Acknowledgement

Not applicable.

Disclosure

J. Specht: Research funding grants: Abbvie, Cascadian Therapeutics, Celgene, Celldex, Genentech, Juno Therapeutics, Merck & Co, Nektar, Novartis, Pfizer, Seattle Genetics, Myriad Pharmaceuticals. L. Pusztai: Advisoray board membership, honoraria: Seattle Genetics (SGEN), Merck, AstraZeneca; Consultancy: Syndax, Almac, Immunogenics; Grant info: NCI, Susan Komen Foundation, Breast Cancer Research Foundation; Research Grants: SGEN, Roche, Merck; Travel expenses: SGEN, Merck, AstraZeneca, Syndax. A. Forero-Torres: Research funding grants: Seattle Genetics; Speaker's bureau: Seattle Genetics. M. Mita, I. Krop: Research funding grants: Seattle Genetics. A. Weise: Research funding: Seattle Genetics. A. Grosse-Wilde, Z. Wang, M. Li, S. Hengel, P. Garfin, G. Means, M. Onsum: Employee and stakeholder: Seattle Genetics. S. Modi: Research funding grants: Daiichi Sankyo, Genentech, Novartis, Seattle Genetics; Speaker's Bureau: Genentech.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

287PD - Oral paclitaxel and HM30181A demonstrate clinical activity in metastatic breast cancer (MBC) patients

Presentation Number
287PD
Lecture Time
09:40 - 09:40
Speakers
  • MING-SHEN DAI (Taipei, TW)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

Intravenous (IV) paclitaxel is approved for the treatment of numerous cancers including MBC. Oraxol (Athenex, USA), is an oral formulation of paclitaxel in combination with a novel, orally active, potent and specific inhibitor of P-gp (HM30181A). Oraxol is expected to be less toxic with comparable efficacy to its iv counterpart. We report the interim results of an ongoing study of Oraxol in MBC patients.

Background

Intravenous (IV) paclitaxel is approved for the treatment of numerous cancers including MBC. Oraxol (Athenex, USA), is an oral formulation of paclitaxel in combination with a novel, orally active, potent and specific inhibitor of P-gp (HM30181A). Oraxol is expected to be less toxic with comparable efficacy to its iv counterpart. We report the interim results of an ongoing study of Oraxol in MBC patients.

Methods

Multicenter, single-arm, open-label, study of Oraxol (HM30181A at 15mg, plus oral paclitaxel 205mg/m2) administered orally for 3 consecutive days/week for up to 16 weeks. Paclitaxel PK was determined in the first and fourth week of Oraxol. Tumor Response by CT/MRI was measured using RECIST criteria 1.1 at weeks 8 and 16.

Trial design

Multicenter, single-arm, open-label, study of Oraxol (HM30181A at 15mg, plus oral paclitaxel 205mg/m2) administered orally for 3 consecutive days/week for up to 16 weeks. Paclitaxel PK was determined in the first and fourth week of Oraxol. Tumor Response by CT/MRI was measured using RECIST criteria 1.1 at weeks 8 and 16.

Results

Sixteen MBC patients have been enrolled with a mean (range) age of 56.9 years (range: 38 - 79 yrs). Most had previous combination chemotherapies and/or monotherapy. There were seven (50%) partial responses and 7 (50%) with stable disease in 14 evaluable patients who had post-treatment CT scans. There was no progressive disease for the patients that reached 16 weeks of treatment. Three patients had treatment-related SAEs (grade ≥3 neutropenia); and there was 1 non-treatment related death. Preliminary PK results showed that the daily mean AUC of oral paclitaxel was similar at week-1 and week-4 (1397 vs. 1137 ng-hr/mL). Other studies have shown that oral paclitaxel can achieve exposure similar to that of IV paclitaxel.

Clinical trial identification

NCT03165955

Conclusions

Oral paclitaxel showed very encouraging activity in MBC patients with acceptable toxicity. PK of oral paclitaxel is reproducible.

Clinical trial identification

NCT03165955.

Legal entity responsible for the study

The authors.

Funding

Athenex, Buffalo, NY.

Disclosure

G. Gerald Fetterly, D.L. Cutler, R. Kwan, D. Douglas Kramer, W-K. Chan: Sockholder and employee: Athenex. T. Hung: Stockholder: Athenex. All other authors have declared no conflicts of interest.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Invited Discussant 285PD, 286PD and 287PD

Lecture Time
09:40 - 09:55
Speakers
  • Alessandra Gennari (Novara, IT)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Q&A led by Discussant

Lecture Time
09:55 - 10:05
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

288PD - PERNETTA – A non comparative randomized open label phase II trial of pertuzumab (P) + trastuzumab (T) with or without chemotherapy both followed by T-DM1 in case of progression, in patients with HER2-positive metastatic breast cancer (MBC): (SAKK 22/10 / UNICANCER UC-0140/1207)

Presentation Number
288PD
Lecture Time
10:05 - 10:05
Speakers
  • Jens Huober (Ulm, DE)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

Dual blockade with P plus T is highly active as 1st-line treatment in patients (pts) with HER2+ MBC. In 2nd line therapy T-DM1 is considered standard of care. We hypothesize that a strategy with dual blockade with T+P without chemotherapy followed by T-DM1 at progression could be less toxic with similar efficacy in terms of overall survival (OS).

Methods

Pts with centrally confirmed HER2+ MBC were randomized 1:1 to receive either P+T alone (arm A) or P+T combined with weekly paclitaxel or vinorelbine (arm B), followed by maintenance treatment with T+P until progression. After progression, T-DM1 was given as second line therapy in both arms. The primary endpoint was OS at 24 months (mo), described by the proportion of successes, along with the exact Clopper-Pearson confidence interval (CI). Secondary endpoints included progression free survival (PFS) and time to failure of strategy (TFS: PD after having received both 1st and 2nd-line treatment or death to any reason).

Results

Between 05/13 and 01/16, 210 pts were enrolled. Median age was 58 years, 63% of pts had lung or liver metastases, 36% of tumors were hormone receptor negative, paclitaxel / vinorelbine was given in 46/59 pts. In both arms, 2-year OS was the same. 61/44 of pts of arm A/B proceeded to 2nd line treatment with T-DM1. There were more hematologic, gastrointestinal, neurological toxicities and more alopecia in arm B. Efficacy results.

Kaplan-Meier estimatorsP+TP+T with chemo
[%/median (95% CI)][%/median (95% CI)]
2-year OS (%)*76.2 (68.4-82.9)*76.2 (68.4-82.9)*
3-year OS (%)73.0 (62.8-80.8)73.1 (62.3-81.2)
1st line PFS (median - mo)#8.4 (7.7-12.0)23.3 (17.6-32.6)
2nd line PFS (T-DM1, median - mo)7.0 (4.3-11.3)5.3 (4.0-10.3)
TFS (median - mo)33.6 (23.2-not reached)48.6 (39.5-not reached)

Binomial with 90% CI reported;

1st CNS metastasis was ignored for this endpoint.

Conclusions

P+T alone as first line treatment followed by T-DM1 is a reasonable therapeutic strategy in HER2+MBC. Despite shorter PFS and TFS survival at 2 and 3 years was not affected and side effects were less frequently seen in the chemotherapy free arm. T-DM1 as second line therapy is active and safe after dual blockade with T+P.

Clinical trial identification

EudraCT: 2012-002556-17.

Legal entity responsible for the study

Sakk-Swiss Group for Clinical Cancer Research.

Funding

Roche.

Disclosure

J. Huober: Travel grants, advisory board: Novartis, Roche, Pfizer, Celgene. P. Weder: Consultant, advisory board: MSD, Roche. B. Thürlimann: Stock ownership (Roche) and advisory board (Roche). E. Brain: Honoraria or consultation fees (Roche). All other authors have declared no conflicts of interest.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

289PD - Lucitanib for the treatment of HR+ HER2- metastatic breast cancer (MBC) patients (pts): results from the multicohort phase II FINESSE trial

Presentation Number
289PD
Lecture Time
10:05 - 10:05
Speakers
  • Rina Hui (Westmead, AU)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30

Abstract

Background

Fibroblast growth factor receptor-1 (FGFR1) gene is amplified in about 15% of HR+ HER2- breast cancer (BC) pts. Lucitanib is an inhibitor of FGFR1 and VEGFR-1,2, and 3.

Methods

HR+ HER2- MBC pts received oral lucitanib in 3 centrally confirmed cohorts: 1) FGFR1 amplified, 2) FGFR1 non-amplified, 11q13 amplified, 3) FGFR1 and 11q13 non-amplified, until intolerable toxicity, disease progression or pt withdrawal. Main inclusion criteria included ECOG PS < 1, at least 1 line and no more than 2 lines of chemotherapy. Primary endpoint was ORR. The study used a Simońs 2-stage design: if > 2 pts responded among 21 pts, 20 additional pts could be enrolled in each cohort. FGFR1 copy number variations (CNV) were determined by FISH and ddPCR, while FGFR1 expression by IHC. Serum FGF23 was assessed by ELISA.

Results

76 pts (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. 92% of pts had received >1 lines of chemotherapy. The most frequent AEs were hypertension (76% grade >3), hypothyroidism (45%), nausea (33%) and proteinuria (32%). ORR were 19% (95%CI: 9-35%), 0% (0-17%), 15% (6-33%) in cohorts 1, 2, 3 respectively. Clinical benefit rates (CR, PR and SD > 24 weeks) were 41% (25.52 - 57.7), 11% (3.10 - 32.8), 27% (13.70 - 46.1) respectively. Exploratory biomarker analyses suggested that pts with high FGFR1 amplification (FGFR1/centromere ratio >4 , n = 16) presented higher ORR than those without high level amplification (n = 37) (25% versus 8%). ORR in pts with FGFR1-high tumors (IHC, H-score >50) was 25% (n = 5/20) while ORR was 8% in FGFR1-low cancers. The 20 patients with FGFR1 membrane over-expression had in average 3-month longer PFS (212[165-NA] days) than other patients (109[57-158] days). Serum FGF23 levels after 14 days of lucitanib were significantly increased from baseline (p < 0.0001), suggesting an effective targeting on FGFR.

Conclusions

While the study was stopped prematurely based on a decision by the sponsor in relation to efficacy and safety signals, the FINESSE trial suggests that lucitanib has antitumor activity in pts with HR+ HER2- MBC. Biomarker analyses generates the hypothesis that pts with high FGFR1 expression could derive more benefit. This population deserves further exploration in large trial.

Clinical trial identification

NCT02053636 Protocol no.: BIG 2-13/CL2-80881-001.

Legal entity responsible for the study

Breast International Group, Brussels, Belgium.

Funding

Servier.

Disclosure

R. Hui: Advisory board member: Merck Sharp and Dohme, AstraZeneca, Novartis, Roche, Bristol-Myers Squibb; Honorarium: Merck Sharp and Dohme, AstraZeneca, Novartis, Roche. C. Poirot, L. Xuereb, M-J. Pierrat: Employee: Servier. H.A. Azim Jr.: Consultancy: Roche; Employment: Innate Pharma. D. Fumagalli, A. Arahmani, P. Bedard: Research funding for the trial to institution: Servier. P.G. Aftimos: Honoraria: Synthon, Boehringer Ingelheim, Macrogenics, Amgen, Novartis; Travel grants: Amgen, Merck, Roche. S. Loi: To institution: Novartis, Bristol Meyers Squibb, Merck, Roche-Genentech, Puma Biotechnology and Pfizer; Consultant (not compensated): Seattle Genetics, Pfizer, Novartis, BMS, Merck, Roche- Genentech. All other authors have declared no conflicts of interest.

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Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Invited Discussant 288PD, 289PD and one LBA TBC

Lecture Time
10:05 - 10:20
Speakers
  • Lisa Carey (Chapel Hill, US)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30
Poster Discussion session - Breast cancer, metastatic Poster Discussion session

Q&A led by Discussant

Lecture Time
10:20 - 10:30
Location
ICM - Room 1, ICM München, Munich, Germany
Date
21.10.2018
Time
09:15 - 10:30