Breast cancer, metastatic  

97P - Phase II trial of eribulin and S-1 combination therapy for advanced or recurrent breast cancer

Presentation Number
97P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Eribulin is a non-taxane microtubule dynamics inhibitor that has been proven to prolong overall survival in patients with breast cancer. S-1, an oral anticancer drug, has demonstrated non-inferiority in overall survival (OS) to taxane as first-line chemotherapy for metastatic breast cancer (MBC). We previouly reported phase I trial results for the combination of these drugs with an overall response rate of 41.7% and median progression free survival (PFS) of 7.6 months. George W et.al (J Clin Oncol 2003) suggested that estrogen receptor negativity, the presence of three or more sites of disease, a short disease-free interval (1 to 24 months), and prior systemic therapy all predicted for impaired overall survival in their multivariate analysis. Considering these factors, we conducted a multicenter phase II study of this combination to further evaluate its safety and efficacy.

Background

Eribulin is a non-taxane microtubule dynamics inhibitor that has been proven to prolong overall survival in patients with advanced and recurrent breast cancer .S-1, an oral anticancer drug, composed of tegafur, gimestat and otastat potassium, has demonstrated non-inferiority in overall survival (OS) to taxane as first-line chemotherapy for metastatic breast cancer (MBC).We previouly reported phase I trial results for the combination of these drugs with an overall response rate of 41.7% and median progression free survival (PFS) of 7.6 months. George W et.al (J Clin Oncol 2003) suggested that estrogen receptor negativity, the presence of three or more sites of disease, a short disease-free interval (1 to 24 months), and prior systemic therapy all predicted for impaired overall survival in their multivariate analysis. Considering these factors, we conducted a multicenter phase II study of this combination to further evaluate its safety and efficacy.

Methods

Recurrent or advanced breast cancer patients previously treated with anthracycline or taxanes were enrolled from September 2014 to May 2016. Patients received Eribulin 1.4 mg/m2 day1 and day8 intravenously and S-1 50 mg/m2 from day1 to day14 orally. Primary objective was to investigate safety and efficacy. Secondary objectives were to evaluate PFS, OS and clinical benefit rate (CBR) using Response Criteria in Solid Tumors (RECIST).

Results

Thirty-two patients were enrolled this trial and 30 patients were evaluable. Objective response rate was 36.7%. There were 3 [10%] complete responses, 8 [26.7%] partial responses and 11 [36.7%] stable diseases. This combination therapy had a manageable safety profiles consistent with the known adverse effects of both drugs. The most common grade3-4 adverse events were neutropenia (22 [73.3%] of 32 patients), leukopenia (13 [43.3%] of 32 patients), febrile neutropenia (3 [9.4%] of 32 patients) and peripheral neuropathy (4 [12.5%] of 32 patients). CBR was 46.7%. The median overall survival and the median PFS was not reached.

Conclusions

We showed tolerability and clinical activity in this combination therapy in a subset of patients with poor prognosis. Eribulin in combination with S-1 may represent a promising treatment option for advanced or recurrent breast cancer patients.

Legal entity responsible for the study

Eisai

Funding

Eisai

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

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

Presentation Number
95O
Presentation Topic
Breast cancer, metastatic
Lecture Time
10:00 - 10:12
Speakers
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.

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Breast cancer, metastatic  

112P - Phase II trial of metronomic combination chemotherapy with oral regimen in heavily pretreated metastatic breast cancer

Presentation Number
112P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Metastatic Breast Cancer with prior anthracycline and taxane exposure is difficult to treat in low resource countries such as India. We explored a combination of capecitabine and cyclophosphamide as oral regimen in treatment of MBC as a palliative regimen to assess the response rate, efficacy, toxicity profile (as primary endpoint) and time to tumor progression (as secondary endpoint) in a phase II study.

Methods

The study was conducted after approval from the institutional ethical committee and in accordance with their regulations. Written informed consent was obtained from all patients prior to screening assessments or enrollment. The median age was 52 years (range 24-69). Performance status at baseline was ECOG 1 in 21 and 2 in 19 patients. There were 23 postmenopausal women. Hormone receptors (ER/PR) were positive in 24 patients, (ER and PR) negative in 14 patients and unknown in 2 patients. HER2 status was positive in 10 patients, negative in 24 patients and unknown in 6 patients. Thirty eight patients had been treated with chemotherapy for metastatic disease and anthracycline exposed in 37 and taxane chemotherapy in 39 patients. Fixed doses of capecitabine (1000mg twice daily) with oral cyclophosphamide (100mg) were given on days 1-14, in a three weekly schedule. Flat dosing of the oral agents was used as per published data indicating that the clearance of both drugs is independent of body surface area. The treatment was repeated at a 3-week interval until disease progression.

Results

A complete response (CR) was obtained in two (5%) of 40 patients, and a partial response in 16 (40%) resulting in overall response rate (ORR) of 45%. Twenty one patients had stable disease (SD) and one had progressive disease (PD). When the treatment responses were analyzed according to hormone receptor status (HR), ORR was 45.8% including two CR and nine PR in 24 patients in HR positives, whereas it was 42.8% including six PR in 14 patients in HR negatives. The ORR in HER2 positive (10 patients) and negative (24 patients) was 20% and 54.1%, respectively. The most common (>20% patients) treatment related adverse events were hand-foot syndrome (82.5%), fatigue (57.5%), nausea (47.5%), elevated liver enzymes (35%), vomiting (27.5%), mucositis (27.5%), diarrhea (22.5%), neutropenia (22.5%), anemia (22.5%). Most treatment related adverse events were grade1/2 in severity. None of the patients had a grade 3 adverse event and there were no patients with febrile neutropenia or treatment-related deaths. Grade 2 hand-foot syndrome was observed in only four patients (12.1%).

Conclusions

In resource limited countries such as India, metronomic chemotherapy is an attractive option in anthracycline/taxane pretreated advanced breast cancer patients because of low cost, good tolerance, ease of administration and sound therapeutic efficacy.

Legal entity responsible for the study

Madras Medical College

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

103P - Efficacy of T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with pertuzumab

Presentation Number
103P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The standard therapy for primary treatment of HER2-positive metastatic breast cancer (MBC) is combination therapy of pertuzumab (PER), trastuzumab (HER) and docetaxel (DTX). Although the effectiveness of trastuzumab emtansine (T-DM1) after HER treatment has been reported, there are few reports on the effectiveness of T-DM1 for patients treated with PER. We retrospectively investigated the effectiveness of T-DM1 on HER2-positive MBC previously treated with PER.

Methods

Between October 2013 and June 2017, 79 patients with HER2-positive MBC were treated with PER. 44 patients were investigated the subsequent treatment. 34 patients received T-DM1, and 10 patients received treatment other than T-DM1 after PER treatment.

Results

Median treatment line was 3.0 (1-9) vs 4.0 (1-9) in the T-DM1 treatment and other than T-DM1 treatment, respectively. The response rate was CR 0% vs 0%, PR 36.0% vs 25%, SD 32.0% vs 62.5%, PD 32.0% vs 12.5%, respectively. The objective response rate was 36.0% vs 20.0%. The clinical benefit rate was 48.0% vs 50.0%. Median time to treatment failure was 6.6 months vs 2.9 months, respectively. There was a significant difference in median overall survival; median not reached vs 19.6 months (p = 0.04).

Conclusions

OS was significantly better with administration of T-DM1 after PER treatment. Based on the results of this study, it was confirmed that efficacy of T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with PER.

Legal entity responsible for the study

Koshi Matsui

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

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

Presentation Number
91O_PR
Presentation Topic
Breast cancer, metastatic
Lecture Time
08:42 - 08:54
Speakers
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.

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Breast cancer, metastatic  

108P - Does non-adherence result in worse clinical outcomes for hormone receptor-positive and HER2-negative metastatic breast cancer in premenopausal women?

Presentation Number
108P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

In this study, we observe the patterns initial palliative treatment for premenopausal patients with HR-positive/HER2-negative MBC and determine if non-adherence to clinical guidelines are associated with worse clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) in the South Korean population.

Methods

A retrospective review was performed for premenopausal patients diagnosed with HR-positive MBC between October 1997 and May 2016 who received palliative systemic treatments at a large tertiary medical center. Survival outcomes were analyzed according to the palliative treatment received prior to disease progression.

Results

The review identified a total of 272 premenopausal patients with HR-positive/HER2-negative MBC. The patients were young (median age, 39 years), as per the premenopausal criteria. Chemotherapy alone was first-line palliative treatment in 78 patients, with endocrine therapy as the initial treatment in 133 patients. In 57 patients, the first line treatment was switched from chemotherapy to endocrine treatment prior to any disease progression. Both progression free survival and overall survival were significantly longer for chemotherapy-endocrine therapy (median PFS 18.2 months and OS 85.2 months) than for chemotherapy-alone (median PFS 12.6 months and OS 45.5 months) or endocrine therapy-alone (median PFS 7.0 months and OS 57.3 months) (all P values < 0.01). In multivariate analysis, chemotherapy-endocrine therapy was an independent predictive value for improved PFS and OS (hazard ratio [HR] 0.33, 95% CI 0.20-0.52, P < 0.001; HR 0.38, 95% CI 0.19-0.73, P = 0.004).

Conclusions

In our study population, chemotherapy alone was not objectively inferior to endocrine therapy as the initial palliative treatment. In addition, chemotherapy followed by endocrine therapy was associated with objective higher response rate than endocrine therapy alone. Further studies should explore the relationship between non-adherent treatment patterns and patient outcomes across the largely premenopausal breast cancer populations across Asian countries.

Legal entity responsible for the study

Prof. Yeon Hee Park

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

98P - Effect of postmastectomy radiotherapy on breast cancer with isolated tumor cells or micrometastases in regional lymph nodes: A propensity score matched analysis using the SEER database

Presentation Number
98P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Postmastectomy radiotherapy (PMRT) has been strongly considered for patients with 1-3 positive axillary nodes (ALNs). In addition, the indications for PMRT are expanding to patients with negative ALNs but have multiple high-risk recurrence factors. However, For patients with isolated tumor cells. We aimed to determine the effects of PMRT on survival of patients with ITCs or ALNs micrometastases of breast cancer.

Methods

We identified patients with ITCs or ALNs micrometastases after mastectomy from the Surveillance, Epidemiology, and End Results database from 2004 to 2014. Overall survival (OS) and breast cancer-specific mortality (BCSM) were compared among patients received PMRT or not, using propensity score-matched analyses. Cox proportional hazards models and competing-risk models were performed in OS and BCSM analyses, respectively.

Results

We identified 11,622 eligible cases. PMRT was administered to 1,728 patients. Treatment was less frequent among patients who were older, patients with high-income, and patients with right-side tumor. OS at 5 years and 10 years were 88.1% and 74.2% in PMRT group, and were 87.8% and 77.3% in non-PMRT group, respectively. Five-year and 10-year cumulative BCSM rate were 6.4% and 12.3% in PMRT group, and were 6.6% and 14.1% in non-PMRT group, respectively. OS and BCSM were unaffected by PMRT after adjusting for multiple confounders (OS, hazard ratio, 0.92; 95% CI, 0.74 to 1.16; BCSM, subhazard ratio, 0.89; 95% CI, 0.67-1.18).

Conclusions

To our knowledge, this is the largest study to date of the effect of radiotherapy on survival in breast cancer with ITCs or ALN micrometastases. In this population-based study, we do not find survival benefit of PMRT on patients with ITCs or ALN micrometastases.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

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

Presentation Number
96O
Presentation Topic
Breast cancer, metastatic
Lecture Time
10:12 - 10:24
Speakers
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.

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Breast cancer, metastatic  

113P - Importance of immunohistochemistry for quick selection of breast cancer patients having BRCA1/2 mutations for their better treatment strategy: Pilot study in eastern India

Presentation Number
113P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

In India, breast cancer is the second most common malignant condition among women. It is hereditary in 10% of cases, the majority related to mutations in the BRCA1 and BRCA2 genes. The presence of BRCA germline mutations in breast/ovarian carcinomas has been shown to have prognostic and therapeutic significance. Identification of tumours with BRCA defects has therapeutic and prognostic implications. Our objective was to assess whether immunohistochemical analysis (IHC) for BRCA is an effective method for the detection of BRCA dysfunction in hereditary breast carcinoma or not.

Methods

We have selected 231 patients for BRCA1/2 mutation detection during Aug.2010 to Oct.2015 from the breast cancer patients attended our hospital, NCRI. After taking written consent 4-5ml peripheral blood and/or operated tissue (where possible) were collected from BC patients. BRCA1/2 mutations were identified by ARMS-PCR, DNA sequencing and whole genome sequencing. We performed IHC staining with BRCA1 and BRCA2 antibody to distinguish tumour status between patients according to their indication of BRCA1 or BRCA2 mutation.

Results

Average age of the patients was 45.87±1.57 yrs. BRCA1/2 mutations were identified in 24 (10.38%) patientsthrough above mentioned methods. Tumour samples fromnine BRCA positive cases and 15BRCA negative cases were chosen for investigation of IHC. Out of 9 samples with BRCA mutations, 7were BRCA immunostainingnegative, with absence of nuclear or cytoplasmic staining. On the otherhand, from the 15 patients negative for mutations in both genes, 12 were positive for BRCA1immunostaining with a clear nuclear immunoreactivity in tumour cells. From ROCcurve analysis, it was found that IHC negativity (area- 0.211, CI: 0.011-0.411) isassociated (p = 0.02) with BRCA positivity.

Conclusions

In conclusion, we observed a high specificity for the prediction of BRCA1/2 carriers withimmunohistochemistry using BRCA antibody. Validation of this assay, using a larger sample, will allow using immunohistochemistry to decide which high-risk patients should be screenedfirst for the BRCA mutation gene.

Clinical trial identification

NA

Legal entity responsible for the study

Netaji Suibhas Chandra Bose Cancer Research Institue

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

104P - Clinical and pathological profile of patients with breast cancer in northwest Pakistani population

Presentation Number
104P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Authors
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer (BC) is the most frequently diagnosed disease and a leading cause of death in females globally. BC is also common in Pakistani females and one out of every nine female is at risk of developing BC. Information on the clinico-pathologic (CP) data of BC is limited especially from the northwest part of Pakistan. The purpose of this study was to profile the CP data of BC. This will clearly help us in assessing the CP characteristics of the disease and in public health intervention measures.

Methods

Data were extracted from consecutive medical files of BC patients at the IRNUM Hospital, Peshawar, Pakistan from 2014 to 2016. Demographic, clinical and pathological data were profiled. Data were analyzed for descriptive statistics, independent sample t test and Chi square test. Logistic regression was performed by stratifying patients according to the disease stage as early stage (stage I and II, ES) and late stage (stage III and IV, LS).

Results

Data of 362 patients with breast cancer was profiled. The mean age at diagnosis was 47.8 years. 8% of the patients were nulliparous and 5.2% of the patients had a positive family history of BC. The most common symptom was a lump in breast (82%), and left breast (54%) was the most common location of tumor. Most of the patients presented with LS disease (65%). ER+, PR+ and HER2+ cases were 62%, 47% and 49% respectively. The tumour was localized in 75% of the cases, while multifocal in 25% of the cases. The mean age (47.8 yrs) in the ES breast cancer is not statistically different from the mean age (47.7 yrs) in the LS breast cancer (p = 0.99). Lymph node positivity is associated with LS disease (p < 0.001) and it predicts LS disease (OR = 17.1, p < 0.001). Vascular invasion and HER2+ are also associated with LS disease (p = 0.06, p = 0.07, trending statistical significance).

Conclusions

Due to delayed consultation, patients present with late stage disease irrespective of age of patients. Thus, there is an urgent need for public health outreach programs directed towards awareness campaigns and the need for routine breast cancer screening. In addition, positive family history may be evaluated as potential risk factors in our population. Finally, a significant number of patients are ER+/PR+ and HER2+, which may promise targeted therapy options.

Legal entity responsible for the study

Office of Research, Khyber Medical University, Peshawar

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic  

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

Presentation Number
92O
Presentation Topic
Breast cancer, metastatic
Lecture Time
09:09 - 09:21
Speakers
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.

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Breast cancer, metastatic  

109P - Literature review of visceral and non-visceral metastatic breast cancer

Presentation Number
109P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (mBC) is an important consideration for their subsequent use in clinical practice. In a systematic literature review, we evaluated differences in outcome regarding progression free survival (PFS), time to progression (TTP), overall survival (OS) and visceral versus non-visceral disease. The impact of HER2- and hormone receptor-status was also considered.

Methods

A systematic literature search (6362 hits) in the meta-Database PubMed was performed for the last 20 years. 257 studies (n = 126,291) were included for further analysis. 69 studies had published data for visceral vs non visceral disease including phase III trials. Out of these 69 studies we selected n = 16 studies (n = 13,083) which looked at the endpoints mentioned above. In order to achieve comparability, we extracted the information of hazard ratios (HR), confidence intervals (CI) and times in weeks (if available) for PFS, TTP, OS of the entire study population, which was divided into three groups: HER2-positive, HER2-negative, unknown HER2 status.

Results

No statistically significant difference in treatment response was found in mBC patients looking at HRs and CIs. Relevant, yet not statistically significant differences were found in the specific response of visceral metastases to modern combination therapies, especially in HER2-positive breast cancer: There was a benefit regarding OS using lapatinib combined with trastuzumab or trastuzumab and docetaxel combined with pertuzumab. Additionally, in two chemotherapy trials, there was a numerical difference between therapy response in visceral vs. non-visceral metastases regarding PFS in the unknown HER2 group, and regarding OS in the HER2 negative group.

Conclusions

In the subgroup analyses, we did not find any significant differences in response rates for visceral vs. non-visceral metastasis. There seems to be a beneficial effect of combination therapies regarding OS in visceral disease. At the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in mBC.

Legal entity responsible for the study

Tahir Mehmood

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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