bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).
Authors: Stebbing Justin , Baranau Yauheni Valerievich , Baryash Valery , Manikhas Alexey , Moiseyenko Vladimir , Dzagnidze Giorgi , Javrid Edvard , Boliukh Dmytro , Stroyakovskiy Daniil , Pikiel Joanna , Eniu Alexandru E. , Komov Dmitry , Zautashvili Zakaria , Morar-Bolba Gabriela , Li Rubi Khaw , Lifirenko Igor , Rusyn Andriy V. , Lee Sang Joon , Lee Sung Young , Esteva Francisco J. 
Published: September 2018

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]
Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC).
Authors: Tolaney Sara M. , Barry William Thomas , Guo Hao , Dillon Deborah , Dang Chau T. , Yardley Denise A. , Moy Beverly , Marcom P. Kelly , Albain Kathy S. , Rugo Hope S. , Ellis Matthew James , Shapira Iuliana , Wolff Antonio C. , Carey Lisa A. , Overmoyer Beth , Partridge Ann H. , Hudis Clifford A. , Krop Ian E. , Burstein Harold J. , Winer Eric P. 
Published: September 2018

511 Background: Retrospective data suggest that patients (pts) with small HER2+ cancers have more than just minimal risk of disease recurrence. The APT trial was designed to address treatment for such pts. We have previously reported 3-yr disease-free survival (DFS) and here we provide an updated analysis with 7-yr DFS. Methods: APT is a single arm multicenter, phase II study of TH. Pts with HER2+ BC (IHC 3+ and/or FISH ratio > 2.0) with negative nodes (a single axillary lymph node micrometastasis was allowed) and tumor size < 3 cm were eligible. Pts received T (80 mg/m2) with H x 12 weekly (w), followed by H (weekly or q3w) x 39w. The primary endpoint was DFS. Recurrence Free Interval (RFI), Breast Cancer Specific Survival (BCSS), and overall survival (OS) were also analyzed. Intrinsic subtyping by PAM50 was performed on the nCounter Analysis system on archival tissue. Results: 410 pts were enrolled from September 2007 to September 2010 and 406 began protocol therapy. 67% had hormone-receptor (HR)+ tumors. Distribution by tumor size: 2% T1mi; 17% T1a; 30% T1b; 42% T1c, and 9% T2 ≤ 3 cm. 6 pts had a nodal micrometastasis. With a median follow-up of 6.5 yrs, there were 23 DFS events observed: 4 (1.0%) distant recurrences, 5 local/regional recurrences (1.2%), 6 new contralateral BC (1.5%), and 8 deaths without documented recurrence (2.0%). The 7-yr DFS was 93.3% (95% CI 90.4-96.2); 7-yr DFS for HR+ pts was 94.6% (95% CI 91.8-97.5) and for HR- pts was 90.7% (95% CI 84.6-97.2). 7-yr RFI was 97.5% (95% CI 95.9-99.1); 7-year BCSS is 98.6% (95% CI 97.0-100); and 7-yr OS was 95.0% (95% CI 92.4-97.7). Ongoing PAM50 testing (n = 227 pts) identified 142 (63%) HER2-enriched; 22 (10%) luminal A, 26 (11%) luminal B, and 20 (9%) basal-like; 17 samples had a poor quality assay. Additional testing and associations with clinical outcomes will be presented at the meeting. Conclusions: These data suggest that TH as adjuvant therapy for node-negative HER2+ BC is associated with few recurrences and only 4 distant recurrences with longer follow-up. Based on these data, if chemotherapy/trastuzumab is given to a pt with stage I HER2+ breast cancer, the TH regimen should be considered a standard treatment. Clinical trial information: NCT00542451.
A phase III, open label, prospective, randomized, multicenter, neoadjuvant study of chemotherapy versus endocrine therapy in premenopausal patient with hormone responsive, HER2 negative, breast cancer (KBCSG 012).
Authors: Kim hee Jeong , Noh Woo Chul , Lee Eun Sook , Kim Leesu , Jung Yongsik , Han Wonshik , Nam Seok Jin , Ahn Sei-Hyun 
Published: September 2018

517 Background: Neoadjuvant endocrine therapy has shown efficacy in hormone-responsive postmenopausal breast cancer patients. We aimed to assess the efficacy and safety of cytotoxic chemotherapy versus endocrine therapy for hormone-responsive lymph node-positive premenopausal breast cancer patients in a neoadjuvant setting. (NCT01622361). Methods: In this phase 3, randomized, double blind, parallel group, multicenter study, we enrolled premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with adriamycin plus cyclophosphamide (AC) followed by taxane (T) or neoadjuvant endocrine therapy with zoladex and tamoxifen. Results: 187 patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed the 24 week neoadjuvant treatment period (n=87, both). More patients in the chemotherapy group had a complete or partial response than did those in endocrine therapy arm on both caliper (chemotherapy 83.9% vs endocrine therapy 71.3%, OR 0.476 95% CI 0.228 to 0.994) and MRI (chemotherapy 83.7% vs endocrine therapy 52.9%, OR 0.219, 95% CI 0.107 to 0.447). Three patient on chemotherapy group (3.4%) and 1 patients (1.15%) on endocrine treatment group showed complete pathologic response. In the patients who had breast cancer with low Ki 67 expression (<20%) on initial biopsy, clinical response on caliper were shown similar on both treatment group (HR 0.958, 95%CI 0.296 to 3.101). Five patients who had no tumor on the breast or lymph node after 24 week neoadjuvant endocrine therapy had higher ER score (all allred score >6), all low grade (1or 2) low Ki 67(≤20%) expression (4/5 patients) on initial biopsy specimen. Conclusions: In premenopausal breast cancer patients, 24 weeks neoadjuvant chemotherapy showed better clinical response than endocrine therapy. Low Ki 67 expression could be a parameter of the endocrine treatment. Clinical trial information: NCT01622361.
Independent validation of stromal uPA in archived tumor samples from the prospectively randomized ABCSG8 trial to provide level 1b evidence for a prognostic value of uPA immunohistochemistry in endocrine-treated postmenopausal breast cancer patients.
Authors: Singer Christian F. , Jahn Stephan W , Rudas Margaretha , Bago-Horvath Zsuzsanna , Fitzal Florian , Greil Richard , Mlineritsch Brigitte , Schmitt Manfred , Filipits Martin , Gnant Michael ,   ABCSG
Published: September 2018

536 Background: We have recently demonstrated that urokinase Plasminogen Activator (uPA), together with its inhibitor PAI-1, have prognostic value in hormone-receptor positive early breast cancer, and can be measured in FFPE archived tumor samples. We have now aimed to validate the prognostic role of uPA protein expression in FFPE archived tumor samples in an independent cohort of endocrine-treated breast cancer patients. Methods: 303 postmenopausal women with hormone receptor–positive, early breast cancer who had received 5 years of endocrine therapy in the prospectively designed ABCSG-08 trial, and in whom FFPE tumor tissue was available, were included in this analysis. Stromal uPA and PAI-1 protein expression was evaluated by immunohistochemistry and correlated with distant recurrence-free survival (DRFS) and overall survival (OS). Results: Stromal uPA was detected in 132 of 297 tumors (44.4%), and 74 out of 269 samples (27.5%) exhibited stromal PAI-1, while co-expression of both proteins was found in 48 of 294 (16.3%) samples. Neither uPA nor PAI-1 expression were associated with tumor size, age, nodal status, grading, or receptor status. Patients whose tumor stroma expressed uPA protein were more likely to have a shorter DRFS (adjusted HR for relapse: 2.78; 95% CI 1.31-5.93; p=0.008 Cox regression analysis) and OS (adjusted HR for death: 1.29; 95% CI 0.86-12.50; p=0.161) than women without uPA expression. No such association was observed for PAI-1 and for the uPA/PAI1 ratio. After a median follow-up of 5.6 years women with uPA-positive tumors experienced a significantly shorter DRFS (93.3% vs 84.8%; p<0.013 log rank test) and tended to have a worse OS (83.0.4% vs 77.3%; p=0.106) compared to women with uPA negative tumors. Conclusions: By confirming the clinical utility of stromal uPA IHC in archived breast cancer samples from an independent prospective randomized trial, we now provide level 1b evidence for a prognostic role of stromal uPA in women with endocrine-responsive early breast cancer.
Which patient characteristics drive treatment decisions in elderly patients with early stage hormone receptor–positive breast cancer?
Authors: Satram-Hoang Sacha , Reyes Carolina M. , Stein Alisha , Hoang Khang Q. , Momin Faiyaz , Cortazar Patricia 
Published: September 2018

538 Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer (BC). We examined treatment patterns and outcomes associated with adjuvant or neoadjuvant therapy among elderly patients (pts) in the US. Methods: The analysis included 18,470 first primary HR+HER2- BC pts from the linked SEER-Medicare database. Pts were diagnosed with Stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, continuously enrolled in Medicare Parts A/B in the year prior to diagnosis, enrolled in Part D in the year after diagnosis, and underwent BC surgery ≤6 months after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival adjusting for pt characteristics. Date of last follow-up was 12/31/2013. Results: There were 13,670 (74%) pts treated with hormonal therapy +/- chemotherapy and 4,800 (26%) untreated. Compared to treated pts, untreated pts were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity, and less genomic testing for risk of recurrence (p<0.0001). In a multivariate analysis, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of genomic testing was associated with a lower risk of death. The Cox model showed a 48% higher risk of death in untreated compared to treated pts (HR=1.48; 95% CI=1.35-1.61). Even in a subset of 8,967 pts with stage I disease, tumor size <2.0cm and grade 1/2; untreated pts had a 22% higher risk of death compared to treated pts (HR=1.22; 95% CI=1.05-1.41). Conclusions: Patients who are older with favorable disease characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to pts who received adjuvant or neoadjuvant therapy. The unmet need among elderly BC pts remains, suggesting that age should not deter guideline-based therapy. [Table: see text]
A randomized phase III trial of docetaxel plus cisplatin or paclitaxel plus carboplatin compared with doxorubicin plus cisplatin as adjuvant chemotherapy for endometrial cancer at high risk of recurrence: Japanese Gynecologic Oncology Group study (JGOG2043).
Authors: Nomura Hiroyuki , Aoki Daisuke , Michimae Hirofumi , Mizuno Mika , Nakai Hidekatsu , Arai Masahide , Sasagawa Motoi , Ushijima Kimio , Sugiyama Toru , Saito Motoaki , Tokunaga Hideki , Omatsu Kohei , Nakanishi Toru , Watanabe Yoh , Saito Toshiaki , Yaegashi Nobuo 
Published: September 2018

5503 Background: The superiority of chemotherapy regimens employing a taxane plus a platinum agent over standard therapy with doxorubicin plus cisplatin (AP) was recently demonstrated for advanced or recurrent endometrial cancer. This multicenter phase III trial evaluated the clinical benefit of taxane plus platinum agent regimens as adjuvant chemotherapy compared with AP for endometrial cancer patients at high risk of recurrence after surgery. Methods: Endometrial cancer patients having a high risk of recurrence and postoperative residual disease < 2 cm were randomly assigned (1:1:1) with stratification by FIGO stage and histologic grade to receive 6 cycles of doxorubicin (60 mg/m2) plus cisplatin (50 mg/m2) on day 1 (AP), docetaxel (70 mg/m2) plus cisplatin (60 mg/m2) on day 1 (DP) or paclitaxel (180 mg/m2) plus carboplatin (AUC 6.0 mg/mL x minute) on day 1 (TC) every 3 weeks as adjuvant chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), adverse events, and tolerability. Results: From November 2006 to January 2011, 788 patients were enrolled from 118 institutions in Japan and were eligible for evaluation. The proportion of patients receiving 6 cycles was 80% for AP, 83% for DP, and 76% for TC, and tolerability of the regimens showed no significant difference. After a median follow-up period of 7.0 years, there was no statistical difference of PFS (P=0.1246) or OS (P=0.6734) among the 3 groups. The 5-year PFS rate was 74.9% for AP, 80.9% for DP, and 74.7% for TC, while the 5-year OS rates were 84.3%, 89.3%, and 88.4%, respectively. Conclusions: There was no significant difference of survival among patients receiving AP, DP, or TC as adjuvant chemotherapy for endometrial cancer. Since each regimen showed adequate tolerability, taxane plus platinum agent regimens may be a reasonable alternative to AP. Clinical trial information: UMIN000000522.
Phase II randomized trial of neoadjuvant (NA) chemotherapy (CT) with or without bevacizumab (Bev) in advanced epithelial ovarian cancer (EOC)‏ (GEICO 1205/NOVA TRIAL).
Authors: Garcia Garcia Yolanda , De Juan Ana , Mendiola Cesar , Barretina-Ginesta Maria Pilar , Prat Aleix , Santaballa Ana , Bover Isabel , Gil-Martin Marta , Manzano Aránzazu , Rubio M Jesus , Romeo Margarita , Arqueros Cristina , Garcia Martinez Elena , Gonzalez Martin Antonio 
Published: September 2018

5508 Background: First line carboplatin(C)-paclitaxel(P) and Bev has proved to be an active combination after primary debulking surgery and improve overall survival in sub-optimal resected advanced EOC patients (pts). However, the role of Bev in the NA setting has not been well defined yet. Methods: We performed a phase II randomized open label multicentric study in pts with high grade serous or endometrioid EOC, FIGO stage III-IV, ECOG 0-2, considered unresectable in whom NA CT and interval debulking surgery (IDS) were planned. Main exclusion criteria were intestinal occlusion and contraindication for Bev. Pts were randomized to 4 courses of triweekly C AUC 6 and P 175 mg/m2 iv alone or with at least 3 courses of Bev 15 mg/kg i.v. every 3w in experimental arm. The primary endpoint was complete macroscopic response (CMR) rate at IDS. Secondary objectives were safety, surgical feasibility, optimal surgery rate (OSR), RECIST 1.1 and CA-125 GCIG response rate. Sample collection for translational research was taken at diagnosis and IDS. After surgery pts in both arms completed 3 additional cycles of CT and Bev, followed by maintenance Bev up to 15 mo. Results: Sixty-eight out of seventy-one evaluable pts. Clinical pts characteristics were well balanced, median age 60.0 y.o and a 33.8% stage IV. No differences in CMR were found at IDS (2/33 Control and 2/35 Bev). Bev arm was favoured in rate of surgical feasibility (66.7 vs 88.6%, p = 0.029), while no differences were found in OSR (63.6 vs 65.7%, p = 0.858) and in number of pts considered unresectable at time of IDS (2 vs 0). Median time from IDS to restarting Bev was 7.1 w. Median PFS was 20.3 mo in both arms, 20.13 mo in control arm and 20.36 mo in Bev arm, HR: 1.14 (IC 95%, 0.656 - 1.994). There were lower rates of serious adverse events (grade 3-4) in Bev arm (69.7 vs 42.9%, p = 0.026). 8 pts presented AE of special interest in Bev arm (3G2 proteinuria, 1G2/1G3 hypertension, 1G3 entero-vaginal fistulae, 1G3 entero-cutaneous fistulae, 1G3 deep venous thrombosis, 1G2 bleeding, 1G1 surgical dehiscence). Conclusions: NACT with Bevacizumab was feasible and improved the surgical outcomes at IDS in pts initially considered unresectable. Clinical trial information: 2012-003883-31.
Evaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes.
Authors: Yates Melinda S. , Timms Kirsten , Daniels Molly S , Oakley Holly D. , Munsell Mark F. , Lanchbury Jerry S. , Lu Karen H. 
Published: September 2018

5511 Background: Recent studies show that germline or somatic BRCA1/2 mutations and homologous recombination (HR) defects can be used to predict response to PARP inhibitors in recurrent ovarian cancer. However, the impact of defects in BRCA1/2 and HR genes on overall clinical outcomes are not yet defined for patients undergoing neoadjuvant chemotherapy (NACT) versus upfront surgical debulking (USD). Methods: Previously untreated ovarian cancer patients were prospectively enrolled under approved IRB protocol. Germline and tumor BRCA1/2 mutation testing and methylation were analyzed when sufficient tumor and blood was available. Mutation in 21 additional hereditary cancer genes (including HR genes) was also evaluated. Tumor HR defects were scored on LOH, telomeric allelic imbalance, and large-scale state transitions (as previously described). Presence of germline or somatic BRCA1/2 mutations, BRCA1 methylation, HR score ≥42, or germline mutation in other HR genes were defined together as HRD positive. Results: Of 299 enrolled patients, 129 (43%) received USD and 170 (57%) received NACT. Patients receiving USD had better outcomes compared to NACT, including overall survival (OS, 65.8 vs 45.2 months, p = 0.0003) and event free survival (EFS, 24.8 vs 15.6 months, p < 0.0001). In the overall cohort, EFS was significantly longer for HRD positive patients vs HRD negative (20.5 vs 16.3 months, p = 0.0268). Patients with somatic and germline BRCA1/2 mutations had longer OS vs BRCA1/2 negative (65.3 vs 46.1 months, p = 0.0403). Overall outcomes were worse in NACT compared to USD, but impact of BRCA1/2 mutations and HR defects was stronger in this group. NACT patients with any HR defect had longer EFS (19.7 vs 14.5 months, p = 0.0247). NACT patients with BRCA1/2 germline mutations had longer OS (65.3 vs 38.3 months, p = 0.0230). NACT patients with BRCA1/2 germline mutation had longer EFS (22.6 vs 14.6 months, p = 0.0047). OS and EFS in USD patients were significantly changed based on only debulking status; mutation or HR status did not have a statistically significant effect. Conclusions: While HR defects and BRCA1/2 mutations influence overall outcomes for ovarian cancer patients, the impact is stronger in NACT compared to USD.
Effect of adoption of neoadjuvant chemotherapy for advanced ovarian cancer on all-cause mortality.
Authors: Melamed Alexander , Fink Günther , Wright Alexi A. , Keating Nancy Lynn , Gockley Allison Ann , del Carmen Marcela G. , Schorge John O. , Rauh-Hain Jose Alejandro 
Published: September 2018

5537 Background: Use of neoadjuvant chemotherapy followed by surgery for advanced epithelial ovarian cancer is controversial in the United States. Methods: Use of neoadjuvant chemotherapy for stage IIIC and IV ovarian cancer has increased gradually in the United States since 2007, but rates of adoption vary by region. Between 2011 and 2012, use of neoadjuvant chemotherapy increased by 27% in the New England and East South Central regions, but remained unchanged in three control regions (South Atlantic, West North Central, and East North Central regions). Employing prospectively collected data from Commission on Cancer-accredited cancer programs in the United States, we used this discontinuity in treatment approach to assess the causal impact of neoadjuvant chemotherapy on all-cause mortality in a quasi-experimental fuzzy regression discontinuity design. Kaplan-Meier curves and proportional hazard models were estimated to compare mortality differences between rapidly-adopting regions and controls. We also conducted a cross-sectional analysis of the relationship between regional use of neoadjuvant chemotherapy and survival. Results: We identified 1,156 women treated for advanced epithelial ovarian cancer during 2011 and 2012 in the two rapidly-adopting regions and 4,878 women in the three control regions. In the rapidly-adopting regions, patients treated in 2012 compared with 2011 had a mortality hazard ratio (HR) of 0.81 (95%CI=0.71-0.94) after adjusting for mortality time trends, while no difference was observed in control regions (HR=1.02, 95%CI=0.93-1.12). Compared with control regions, we observed larger declines in 90-day surgical mortality (7.0% to 4.0% versus 5.0 to 4.3%, p=0.01) and in the proportion of women not receiving surgery and chemotherapy (20.0% to 17.4% versus 19.0 to 19.5%, p=0.04) in rapidly adopting regions. Cross-sectional analysis confirmed that treatment in regions with greater use of neoadjuvant chemotherapy was associated was lower mortality (p=0.001). Conclusions: Adoption of neoadjuvant chemotherapy for advanced epithelial ovarian cancer in New England and East South Central regions led to a sizable reduction in mortality within three years after diagnosis.