Background

The subanalysis of prospective randomized trials of E suggested E suppressed development of new lesion [NL] and it led to improvement of overall survival (Twelves, BCRT, 2015), however, behaviors of disease in real-world patients (pts) have not been well discussed.

Methods

Outcomes of HER2-MBC pts who received E at our institute from November 2011 to present were reviewed. Statistical analyses were performed using the chi-square test, the Kaplan-Meyer method.

Results

We identified total 128 (90 ER+, 38 ER-) HER2-MBC who received E at least 2 cycles in our institute. Median age at the initiation of E were as follows; overall, 58 (range 30-77); ER+, 60 (30-77); ER- 55.5 (32-71). Median number of regimens prior to E were as follows; overall, 1 (range 0-8); ER+, 1 (0-6); ER-, 2 (0-8). While all pts had a history of anthracycline and/or taxane in ER- subset, Number of involved organ were 2 (1-5) in overall and both subsets and no significant difference was seen in the pattern of visceral involvement. Most of (122/128, 95.5%) the pts was discontinued E therapy, and median time-to-treatment failure (TTF) were as follows; overall, 125.0 days (95% confidence interval [CI] 43.0-328.0); ER+, 134.0 days (95%CI 62.0-314.0); ER-, 104.0 (95%CI 42.0-230.0). Reasons for the discontinuation of E were as follows; progression of known lesion(s), 77 (63.1%); development of NL, 27 (22.1%), decrease of performance status, 11 (9.0%); intolerable toxicity, 6 (4.9%); other, 1 (0.9%). In ER- subset, development of NL was more frequently seen compared to ER+ subset, however, it was not statistically significant. (7/20 vs 10/67, P = 0.12, chi-square). Multivariate cox regression analyses disclosed some risk factors for TTF as follows; liver metastasis, hazard ratio [HR] 0.39, P < 0.05; soft tissue metastasis, HR 0.53, P < 0.05; ≥3 involved organs, HR 2.99, P < 0.05; taxane for early breast cancer, HR 2.50, P < 0.05. When limited to ER+ pts who received E as 2nd-line therapy (N = 40), only one (2.5%) pt developed NL and there was a positive relationship between TTF and OS after E (Spearman's roh=0.64, p < 0.0001).

Conclusions

Our single institutional review with some limitations disclosed eribulin monotherapy revealed equivalent effect shown in prospective studies.

Legal entity responsible for the study

Junichiro Watanabe

Funding

None

Disclosure

J. Watanabe: Advisory board member of Eisai Co., Ltd. Honoraria from Eisai Co., Ltd.

Background

Breast cancer has become the most common cancer in Thai women since 2005. Unfortunately two thirds of the patients were diagnosed at advanced breast cancer (ABC) stage. Furthermore, most of these women were under the Universal Coverage by the government which does not provide sufficient coverage for certain critical medical treatments for ABC patients. The cost of treatments is even more of a pressing issue in Thailand. This study aimed to evaluate the cost-effectiveness of exemestane (EXE), a steroidal aromatase inhibitor (SAI), as treatment therapy following adjuvant non-steroidal aromatase inhibitor (NSAI) for hormonal responsive ABC in Thailand.

Methods

A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes using a social cost and benefit perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy and cost of EXE and chemotherapy were based on a clinical trial that included a total of 18 post-menopausal hormonal responsive ABC patients. Utility values were derived directly from all patients using EQ-5D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty.

Results

In base case analysis, the EXE group had better clinical outcomes and lower lifetime costs. The incremental cost per QALY gained was US $-2,747 per QALY. The acceptability curve showed that the probability of EXE being cost-effective was 97% at the willingness to pay of 1 time of Thai Gross National Income per capita (GNI per capita), approximately US $4,673 per QALY gained.

Conclusions

At a social cost of paying 1 GNI per capita, EXE is highly effective and cost-saving regimen for the first-line treatment of post-menopausal ABC with hormone positive receptor in Thailand. This study provides key relevant information aiding policy makers to make informed decision making regarding resource allocation to include EXE into reimbursement plan.

Legal entity responsible for the study

Faculty of Medicine, Chiang Mai University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Eribulin mesylate (ERI) demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received 2 or more chemotherapy regimens. Recently, we conducted Phase II study about the efficacy of ERI with trastuzumab (ERI+TRA) as late-line therapy for locally advanced or metastatic HER2-positive breast cancer (UMIN000012350), and reported that objective response rate (ORR) and median progression-free survival (mPFS) were 17% and 4.6 months. However, some patients who received prior pertuzumab (PER) and/or T-DM1 were enrolled in that study, there are limited data on the efficacy of ERI+TRA in those patients. The aim of this study was to assess the efficacy of this combination therapy based on prior PER and/or T-DM1 use.

Methods

In primary phase II study, patients with locally advanced or metastatic HER2 positive breast cancer who previously received at least one chemotherapeutic regimen, received ERI at 1.4 mg/m² intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial TRA dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of TRA on day 1 of each subsequent cycle. ORR, clinical benefit rate (CBR) and PFS were assessed in patients who had and had not received prior PER and/or T-DM1.

Results

Thirty-six patients (median age: 60.5 years) received ERI+TRA. 69.4% (n = 25) had previously treated with prior PER and/or T-DM1, defined as ‘prior’ patients. Remaining 30.6% (n = 11) without both agents were defined as ‘non-prior’ patients. In prior patients compared with non-prior patients, median number of prior treatment regimens was 4 (range, 1‐8) versus 3 (range, 1-7), respectively; ORR was 12.0% versus 27.3%, respectively; CBR was 24.0% versus 54.5%, respectively; mPFS was 4.3 versus 9.7 months, respectively.

Conclusions

ERI+TRA demonstrated lower efficacy than in non-prior patients, but CBR and PFS were 24.0% and 4.3 months, which was considered to be a clinically relevant treatment option in patients who received prior PER and/or T-DM1.

Clinical trial identification

UMIN000012350.

Legal entity responsible for the study

Nagoya Surgical Oncology Group

Funding

Eisai

Disclosure

All authors have declared no conflicts of interest.

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.

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.

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 1^st-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.

Background

It is unclear whether perioperative fluoropyrimidine (FP) use impacts the efficacy of capecitabine in advanced breast cancer treatment.

Methods

Medical records of patients with advanced breast cancer who received capecitabine between 2008 and 2016 at National Cancer Center Hospital (Tokyo, Japan) were reviewed. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared between a FP group (prior perioperative FP use) and a non-FP group (no prior FP use). To evaluate the effect of prior perioperative FP use on survival outcomes, hazard ratios (HRs) for PFS and OS were estimated for the FP group compared with the non-FP group.

Results

A total of 289 patients (FP group: n = 106; non-FP group: n = 183) were analyzed. Patient characteristics were similar between the two groups. The median recurrence-free interval (RFI) was 3.94 (range: 0.27-20.11) years in the FP group and 4.24 (range: 0.27-27.07) years in the non-FP group (p = 0.402). The FP group had poorer PFS than the non-FP group (univariate HR: 1.33; 95% confidence interval [CI]: 1.03-1.72, p = 0.028; multivariate HR: 1.33; 95% CI: 1.02-1.73; p = 0.034). However, OS was similar between the groups (univariate HR: 1.16; 95% CI: 0.84-1.62; p = 0.368; multivariate HR: 1.06; 95% CI: 0.74-1.51; p = 0.755). Multivariate HRs for PFS for the FP group with short RFI and long RFI (cutoff: RFI=4 years) separately were 1.56 (95% CI: 1.06-2.28; p = 0.025) and 1.20 (95% CI: 0.84-1.70; p = 0.326), respectively. With different cutoffs (RFI=3, 4, and 5 years), the ranges of adjusted HRs for PFS were 1.32-1.67 with short RFI, and 1.00-1.25 with long RFI. A trend for larger HR for the FP group with short RFI than with long RFI was also seen for OS with different cutoffs of RFI. The response rate (FP group vs. non-FP group) was 21.0% vs. 14.8% (p = 0.306), and the disease control rate was 59.9% vs. 54.5% (p = 0.422). There was no significant difference in AEs between the two groups.

Conclusions

Capecitabine can be used for patients with advanced breast cancer with FP use history, as OS does not correlate with prior FP use. For patients with FP use history, RFI may be a relevant factor for treatment selection.

Legal entity responsible for the study

National Cancer Center Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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.

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.

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.

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.Table: 92O

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.

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.