S-A Im

Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m−2 at week 1 and 250 mg m−2 weekly thereafter until disease progression. Oxaliplatin (100 mg m−2) and leucovorin (100 mg m−2) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m−2) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1–65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5–6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-α levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.

FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study

Background:In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials.Methods:FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed.Results:The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour.Conclusion:A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive.

Abstract S1-03: Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer

Background The humanized monoclonal antibody (mAb) trastuzumab (H) + chemotherapy (chemo) prolongs disease-free survival (DFS) in patients (pts) with HER2-positive breast cancer (BC) in the adjuvant setting. Vascular endothelial growth factor (VEGF-A), one central regulator of angiogenesis, is a downstream target of HER2. Tumors overexpressing HER2 also overexpress VEGF-A and exhibit increased angiogenic potential. Combining H with the anti-VEGF-A mAb bevacizumab (B) significantly decreased tumor volume vs B or H alone in HER2-positive xenograft models and demonstrated efficacy in phase 2 studies. In the phase 3 AVEREL study in pts with HER2-positive metastatic BC, adding B to H + docetaxel (T) led to a non-significant increase in a duration of PFS and objective response rates. Chemo plus H±B is now explored in this large phase 3 trial to assess the impact of VEGF-A blockade on residual or micrometastatic disease in the adjuvant setting. Methods BETH (NCT00625898) is a randomized, phase 3, open-label study evaluating the addition of B to 2 different H-chemo regimens. Pts had centrally-confirmed HER2-positive BC (FISH+ and/or IHC 3+), ECOG PS 0-1, unilateral invasive breast adenocarcinoma, total mastectomy or lumpectomy, and LVEF ≥55%. Prior therapy with anthracyclines, taxanes, carboplatin (C), H or B for any malignancy or radiotherapy, chemo, and/or targeted therapy for the currently diagnosed BC were not permitted. Pts were stratified by center, hormone receptor status (ER and/or PR-positive, ER/PR-negative), and axillary lymph node status (0, 1-3, 4+) before inclusion into 1 of 2 chemo cohorts, and then randomized. All pts were recruited by investigators from the Translational Research in Oncology (TRIO/CIRG), the National Surgical Adjuvant Breast and Bowel Project (NSABP) or a group of independent sites. Cohort 1 (3231 pts) included pts receiving 6 cycles of TCH±B followed by H±B for 1 yr after the first dose. Cohort 2 (278 pts) included pts from some independent sites electing to use anthracycline-based therapy and these pts received 3 cycles of TH±B followed by 3 cycles of 5-fluorouracil, epirubicin, cyclophosphamide followed by H±B to complete 1 yr of treatment. T was given at 8 mg/kg IV loading dose, 6 mg/kg IV q3w thereafter; B was given at 15 mg/kg IV q3w. The primary endpoint is invasive DFS (IDFS) for B-containing vs. non-B-containing regimens. Secondary endpoints are IDFS within chemo cohorts, DFS, overall survival, recurrence-free interval (RFI), distant RFI, safety including specific cardiac assessments, and the identification of predictive biomarkers for B. The sample size was determined to test the hypothesis of interest, both in the faster accruing cohort and overall. With 3509 pts enrolled, the trial will have 85% power to detect a HR of 0.70 favoring the addition of B overall, irrespective of chemo regimen. With ∼3000 pts in the faster-accruing cohort, the study will have 80% power to detect a hazard ratio (HR) of 0.70 at a 2-sided alpha of 0.05. Median duration of follow-up will be 36 months in Jun 13, cut-off date of the primary analysis. Initial efficacy, safety, and plasma marker analyses will be reported. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S1-03.

Biomarker analysis in stage III–IV (M0) gastric cancer patients who received curative surgery followed by adjuvant 5-fluorouracil and cisplatin chemotherapy: epidermal growth factor receptor (EGFR) associated with favourable survival

The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III–IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282–0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III–IV (M0) gastric cancer patients who received adjuvant FP chemotherapy.

Abstract S1-07: A phase III trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04)

Background Patients (pts) with pathologic residual invasive disease after neoadjuvant chemotherapy (NAC) have an intermediate or high-risk for relapse. It is not clear whether further systemic chemotherapy is beneficial for these pts. CREATE-X is a multicenter open-label randomized phase III trial evaluating this major clinical issue using capecitabine (X) in pts without pCR after NAC (UMIN000000843). We have shown previously that the addition of 8 cycles of X to standard adjuvant therapy is feasible and well tolerated (Ohtani S, et al. SABCS2013#P3-12-03). We report the first efficacy results from a pre-planned interim analysis after 2-year follow-up. Methods Pts with HER2-negative residual invasive cancer after anthracycline- and/or taxane-containing NAC were randomized to standard treatment (RT, hormone therapy (HT) as appropriate) with or without 8 cycles of X (1250 mg/m2 bid, days1–14,q3w). Pts with hormone receptor (HR)-positive disease received HT either with or after X, according to each center9s prespecified standard practice. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS), safety, and cost-effectiveness. It was originally planned to enroll 450 pts in each arm in order to detect a HR 0.74 improvement in the X arm with 80% power and a two-sided 5% significance level. We planned one interim analysis of DFS at 2-years after all pts enrolled using Lan-DeMets alpha spending function method (O9Brein-Fleming type). Results Between Feb 2007 and Jul 2012, 910 pts were randomized, with 455 pts to receive X. The full analysis consisted of 902 pts who matched the inclusion criteria. Baseline characteristics were well balanced. The median age was 48 years in both arms; 63.5% were HR-positive. In the investigational arm, HT was given with X concurrently in 200 pts and after X in 24 pts. The relative dose intensity of X was 78.8%. At the time of the interim analysis, DFS events were confirmed in 81 (18.8%) in the investigational arm and 109 (24.7%) in the standard arm, and OS events were 28 (6.5%) and 41 (9.3%), respectively. On Kaplan-Meier analysis, 2-year DFS was 87.3% for the arm with X and 80.5% for no X (HR:0.688, 98.66%CI: 0.479-0.989, log-rank P=0.001). The tendency for improvement of OS by adding X was also confirmed; 2-year OS was 96.2% and 93.9%, respectively (HR: 0.658, 95%CI: 0.407-1.065, log-rank P=0.086). In the experimental arm with X, grade 3/4 toxicities included HFS (11%), neutropenia (9%), diarrhea (3%), and fatigue (1%); all were controllable. No SAE was related to X administration. Because the study met the primary endpoint, an independent data monitoring committee recommended discontinuation of the study. Conclusions: The clinical utility of X in the adjuvant setting for breast cancer pts has been proven to improve the prognosis based on the pathological response-guided strategy. Tolerability was consistent with the established safety profile of X in mBC. The benefit to risk balance of the addition of 8 cycles of X to standard adjuvant therapy seems to be satisfied. This evidence might allow the development of personalized individualized treatment based on the response to primary systemic therapy. Citation Format: Toi M, Lee S-J, Lee ES, Ohtani S, Im Y-H, Im S-A, Park B-W, Kim S-B, Yanagita Y, Takao S, Ohno S, Aogi K, Iwata H, Kim A, Sasano H, Yokota I, Ohashi Y, Masuda N. A phase III trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S1-07.

Abstract P3-12-03: Adjuvant capecitabine in breast cancer patients with pathologic residual disease after neoadjuvant chemotherapy: First safety analysis of CREATE-X (JBCRG-04)

Background Patients (pts) without pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have a poor prognosis compared with pts achieving a pCR with NAC. It is not clear whether further systemic chemotherapy is beneficial for pts with no pCR. CREATE-X (UMIN000000843) is an ongoing collaborative Korean (KRN)/Japanese (JPN) prospective multicenter open-label randomized phase III trial evaluating this clinical question using capecitabine (X) in pts with no pCR after NAC. We report first safety results, focusing on hand-foot syndrome (HFS), the timing of radiotherapy (RT) and hormone therapy (HT), and differences between KRN and JPN pts. Methods Pts with residual invasive cancer after anthracycline- and/or taxane-containing NAC were randomized to standard post-surgical treatment (RT, HT as appropriate) with or without 8 cycles of X (1250 mg/m2 bid, days 1–14 q3w). RT was given before or after X. Pts with hormone receptor (HR)-positive disease received HT either with or after X, according to each center9s prespecified standard practice. After evaluation of the tolerability of 6 cycles of X in the first 50 pts, the independent data monitoring committee recommended extending X to 8 cycles. Results Between Feb 2007 and Jul 2012, 910 pts were enrolled (304 in Korea, 606 in Japan). At the time of data cut-off (May 20, 2013), data were available from 866 pts. Median age was 48 years in both arms. In the investigational arm, RT was given before X in 260 pts and after X in 33 pts; 73 pts received prophylactic vitamin B6 (VB6). In HR-positive pts HT was given with X in 200 pts and after X in 24 pts. The relative dose intensity of X was 85.7% in JPN pts and 95.2% in KRN pts. Grade (G) 3/4 neutropenia, HFS (G3 only), fatigue, and diarrhea were significantly (p Conclusions Addition of 8 cycles of X to standard adjuvant therapy is feasible and tolerable, resulting in a modest yet acceptable increase in toxicities. The timing of RT and HT administration relative to X influenced the incidence of adverse events. HFS was more common in JPN than KRN pts, although further investigation of the potential cause of this difference is required. These findings should be interpreted in light of efficacy data, expected in 2015. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-03.

Abstract P4-07-08: The prognostic significance of ataxia-telangiectasia-mutated (ATM) and p53 expression in breast cancer

The purpose of this study was to investigate the correlation of ataxia-telangiectasia-mutated (ATM) protein and p53 expression with clinicopathological features and prognosis in patients with sporadic breast cancers. The expression of ATM and p53 was determined by immunohistochemistry in 420 surgically resected breast cancers. Loss of ATM was observed in 126 out of 407 evaluable cases (31.0%), and was significantly associated with aggressive features with large tumor size, lymph node metastasis, higher tumor grade, and negativity of ER and/or PR. ATM loss was associated with a significantly shorter disease-free survival (DFS) (p = 0.019). Abnormal p53 expression was found in 39.3% of tumors (157 out of 400), conferring a worse DFS as well (p = 0.002). When investigated together, combined ATM and p53 expression status were associated with a worse DFS (p = 0.002). On multivariate analysis, ATM loss and abnormal p53 expression status was an independent predictor of poorer DFS (intact ATM and normal p53 vs. ATM loss and abnormal p53, HR 3.350; 95% CI 1.496 - 7.502; p = 0.003). Furthermore, in patients treated with adjuvant anthracyclines, either p53 alone or p53 combined with ATM significantly influenced DFS (p = 0.004, p = 0.015, respectively). The present study demonstrates that expression of ATM and p53 is an independent prognostic marker in breast cancers, and might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy. Citation Format: Suh KJ, Ryu HS, Lee K-H, Im S-A, Kim T-Y, Kim H, Yang Y, Moon H-G, Han S-W, Oh D-Y, Han W, Kim T-Y, Park IA, Noh D-Y, Bang Y-J. The prognostic significance of ataxia-telangiectasia-mutated (ATM) and p53 expression in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-07-08.

Abstract P4-13-01: PALOMA3: Phase 3 trial of fulvestrant with or without palbociclib in pre- and postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy—confirmed efficacy and safety

Background: Selective estrogen receptor modulators and aromatase inhibitors (AI) (+LHRH agonists [premenopausal]) are standard of care (SOC) for hormone–receptor–positive (HR+) metastatic breast cancer (MBC). Many HR+ MBC patients (pts) get limited benefit from adjuvant or advanced endocrine therapy (ET) and develop endocrine resistance, refractory disease. HR+ BC growth relies on cyclin dependent kinases 4/6 that promote G1–S phase cell cycle progression. Palbociclib (PAL) with ET showed efficacy in HR+/HER2– MBC (Turner et al, 2015). We report updated safety and efficacy from PALOMA3 with longer follow–up, focusing on degrees of clinically defined endocrine resistance. Methods: Pts with HR+/HER2– MBC that progressed on prior ET were randomized 2:1 to PAL (125 mg/d oral [3 wks drug, 1 wk off]) + fulvestrant (F, 500 mg, SOC) +/– goserelin or placebo (PLB)+F. One line of chemotherapy (CT) for MBC was allowed. Pt stratification: prior ET sensitivity; visceral metastases; menopausal status. Primary endpoint (EP) was investigator–assessed progression–free survival (PFS). Secondary EP: overall survival, response assessment, patient–reported outcomes, safety. Results: By March 2015, median follow–up was 8.9 mo. 521 pts were randomized (PAL+F, 347; PLB+F, 174). Baseline characteristics were balanced. Median PFS was 9.5 (95% CI 9.2–11.0) mo (PAL+F) vs 4.6 (3.5–5.6) mo (PLB+F) (HR 0.46 [0.36–0.59], P Conclusion: Mature efficacy confirmed superior PFS and demonstrated significantly improved clinical response and CBR by the combination of ET and Palbociclib. It also consistently showed therapeutic benefit irrespective of menopausal status and various degrees of endocrine sensitivity. Safety profile is favorable. PAL+F may be an effective option for HR+ MBC pts. Funding: Pfizer. Citation Format: Cristofanilli M, Bondarenko I, Ro J, Im S-A, Masuda N, Colleoni M, DeMichele AM, Loi S, Verma S, Iwata H, Huang Bartlett C, Zhang K, Puyana Theall K, Turner NC, Slamon DJ. PALOMA3: Phase 3 trial of fulvestrant with or without palbociclib in pre- and postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy—confirmed efficacy and safety. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-01.

Abstract OT3-01-10: A prospective, open-label, single-arm, multi-center, phase II exploratory study to evaluate the efficacy and safety of poziotinib (NOV120101) in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens

Background: Poziotinib is a novel, oral, irreversible pan-HER inhibitor that has shown promising clinical activity in Phase 1 studies of patients (pts) with advance HER2 positive breast cancer who have failed at least 2 prior lines of HER2-directed therapy. A Phase 2 study of poziotinib was initiated in Korea in March 2015 in pts with HER2+ metastatic breast cancer. This phase 2 study is designed to seek accelerated approval for poziotinib for the treatment of metastatic breast cancer in Korea. Trial Design: Prospective Phase 2, open-label, single-arm, multi-center study in pts with recurrent, Stage IV breast cancer with HER2-overexpression who had received at least 2 prior HER2-directed regimens Eligibility Criteria: Histologically confirmed breast cancer patients, at least 19 years of age, with confirmed HER2 positive evaluable tumors (per RECIST, 1.1) who have adequate hematologic, renal, and hepatic function and have failed at least two HER2-directed regimens that included a taxane-containing anticancer chemotherapy, with a life expectancy of at least 12 weeks. Specific Aims: The Primary Efficacy Endpoint of the study was Progression-Free Survival (PFS). The Secondary Efficacy Endpoints included: PFS rate at 12 weeks post-dose; Objective Response Rate (ORR) including Complete Response (CR) and Partial Response (PR) rates; Disease Control Rate (DCR) including CR, PR, and Stable Disease (SD); Duration of Disease Control; Overall Survival (OS); Time to Progression (TTP); Time to Objective Response and Duration of Objective Response. The Exploratory Endpoints included: Population Pharmacokinetic (PK) Profile and Exploratory Genomic and Biomarker Analyses. Statistical Methods: In the randomized, multicenter, 2-arm, open-label study of trastuzumab emtansine (TH3RESA18), the median PFS was shown to be 3.3 months in subjects with optimal treatment per Investigator9s Choice. This ongoing study with poziotinib expects a median PFS of 4.5 months based on data from a previous Phase 1 study of poziotinib (NOV120101). Based on the following assumptions, a 5% one-sided significance level, and 80% power, and 2 months of accrual and 12 months of follow-up, 66 subjects will be required. Accounting for a 10% drop-out rate, a total of 74 subjects will be recruited into this ongoing Phase 2 study. Present Accrual and Target Accrual: 17 patients enrolled as of May 20, 2015 with a total target enrollment of 74 patients Contact information: ClinicalTrials.gov Identifier: NCT02418689. Citation Format: Park Y-H, Jung KH, Sohn JH, Lee KS, Lee KH, Kim J-H, Kim J-Y, Jung J, Han H, Park W-Y, Im S-A. A prospective, open-label, single-arm, multi-center, phase II exploratory study to evaluate the efficacy and safety of poziotinib (NOV120101) in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-10.

Abstract P4-13-19: Poziotinib, an oral, irreversible pan-HER inhibitor, demonstrates promising clinical activity in metastatic HER2 positive breast cancer patients

Background: Poziotinib is a novel, oral, irreversible pan-HER inhibitor that has been studied in two completed Phase 1 clinical trials in patients with advanced solid tumors (HM-PHI-101; HM-PHI-102) and is currently being studied in several Phase 2 clinical trials. Preclinical studies have shown poziotinib to be more potent in vitro than other EGFR- and HER2-directed tyrosine kinase inhibitors. This study collates the clinical experience of poziotinib in patients with advanced HER2 positive breast cancer from the two completed Phase 1 trials. Results: The maximum tolerated dose (MTD) and safety of poziotinib were evaluated in HM-PHI-101 (once daily, Day 1-14 q3 weeks) and in HM-PHI-102 (continuous dosing). The Dose Limiting Toxicity (DLT) was diarrhea in both studies. Anti-diarrheal medicine was allowed, but prophylactic anti-diarrheal therapy was not used. The most frequently reported Grade 3 AE was diarrhea (40%). The MTD for intermittent dosing of poziotinib was 24 mg and the MTD for continuous dosing was 16 mg. The Dose Limiting Toxicity (DLT) was diarrhea in both studies. Anti-diarrheal medicine was allowed, but prophylactic anti-diarrheal therapy was not used. In total, 10 patients with HER2 positive metastatic breast cancer were treated in the two trials (median age 56.5, range 30-69). These patients were heavily pretreated (median number of previous treatment regimens 5, range 3-9), and all patients had failed treatment with both trastuzumab and lapatinib. The Overall Response Rate (ORR) in these breast cancer patients was 60% and Clinical Benefit Rate (CBR) was 80%. The median duration of response was 32.5 weeks (range 18 - 56 weeks). Two patients in the early dose cohorts of 1 or 2mg had progressive disease. The median progression free survival (PFS) was 28 weeks (6, 6, 12, 17, 25, 31, 37, 49, 57, and 98 weeks). Conclusions: Poziotinib showed very promising clinical activity in Phase 1 patients with metastatic HER2 positive breast cancer, who had been heavily pretreated and failed two prior HER2-directed therapies. The ORR in this patient population was 60% and the CBR was 80% in these two early dose finding studies. The AEs observed in these studies was consistent with other pan-HER and EGFR inhibitors. While the majority of DLT cases involves diarrhea, toxicity of other adverse events was relatively tolerable. An intermittent dosing schedule seemed appropriate for poziotinib. Multiple Phase 2 studies with poziotinib are ongoing in patients with breast cancer and other solid tumors. Citation Format: Im S-A, Kim J-H, Lee K-H, Kim SH, Oh D-Y, Kim Y-J, Han S-W, Kim T-Y, Kim T-Y, Jung J, Bang Y-J. Poziotinib, an oral, irreversible pan-HER inhibitor, demonstrates promising clinical activity in metastatic HER2 positive breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-19.