bluuebunny/crossref_metadata_2025_split huggingface dataset:
The initial report of RTOG 0524: Phase I/II trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer.
Authors: Michaelson M. Dror , Hu Chen , Pham Huong T. , Dahl Douglas M. , Wu Chin-Lee , Whittington Richard M. , Swanson Gregory P. , Vuky Jacqueline , Lee R. Jeffrey , Souhami Luis , Chang Brian K. , George Asha , Sandler Howard Mark , Shipley William U. 
Published: February 2017

LBA287 Background: Most patients (pts) with muscle-invasive bladder urothelial carcinoma (UC) undergo definitive local treatment with radical cystectomy. Up to 50% of pts with UC overexpress HER2/neu, which may be associated with reduced responsiveness to chemoradiation and reduced survival. Many pts with UC have comorbidities that preclude surgery, creating a traditionally underserved population with worse outcomes. RTOG 0524 evaluated the safety and efficacy of trimodality, organ-preserving therapy in pts not suitable for cystectomy. Methods: Pts with invasive bladder UC (stages T2-T4a, N0-1, M0) underwent cystoscopic tumor resection. Tumors were analyzed by HER2/neu immunohistochemistry (IHC) and assigned to chemotherapy group I (IHC 2+ or 3+; paclitaxel and trastuzumab) or II (IHC negative or 1+; paclitaxel alone). Concurrent weekly paclitaxel (50 mg/m2), weekly trastuzumab (group I only) and daily radiation (64.8 Gy total in 36 fractions) were given for seven consecutive weeks. Results: 21 eligible patients were entered in group I and 47 in group 2, with median ages of 80 and 73, respectively. The primary endpoint was acute protocol-defined toxicity related to treatment. Acute toxicity was observed in 7/21 pts (33%) in group I and 14/47 pts (30%) in group II. Most common grade > 3 adverse events in groups I and II were marrow suppression (43% and 17%), diarrhea (33% and 30%), and hyponatremia (14% and 4%). Three deaths on study were attributed to colonic perforation, pneumonia, and sudden death. Radiation completion rates were 72% and 85% in the two groups, and full-dose chemotherapy completion rates were 52% and 51%. Evaluation by cystoscopy and/or tumor biopsy at 12 weeks noted complete response in 9/13 pts (69%) in group I, in 19/33 pts (58%) in group II, and was not performed in the remaining pts. Conclusions: Trimodality bladder-preserving therapy is an appropriate treatment in noncystectomy candidates with invasive UC. The response rate for HER2/neu-targeted therapy is encouraging but may increase certain adverse events in this challenging population. Clinical trial information: NCT00238420.
ASET study: Long-term follow-up data of patients with metastatic renal cell carcinoma treated with MGN1601.
Authors: Gruenwald Viktor , Weikert Steffen , Schmidt-Wolf Ingo G. H. , Hauser Stefan , Magheli Ahmed , Schroff Matthias , Schmidt Manuel , Wittig Burghardt 
Published: February 2017

LBA399 Background: The cell-based therapeutic cancer vaccine MGN1601 is a fixed combination of allogeneic tumor cells modified via MIDGE vectors to express IL-7, GM-CSF, CD80, and CD154 plus the immunomodulator dSLIM. In the ASET trial heavily pretreated patients with metastatic renal cell carcinoma (mRCC) were enrolled to assess safety, immunological effects, and clinical efficacy of MGN1601. Methods: The ASET study was a multicenter, single-arm phase 1/2 study. The treatment phase consisted of 8 intradermal vaccinations over 12 weeks. Following evaluation, patients with at least disease stabilization entered an extension phase (EP, 5 vaccinations over 120 weeks). Overall, 19 patients were included and received at least one MGN1601 injection (ITT); the majority (N=17) had ≥3 lines of previous therapy. Results: Of 19 patients, 10 (55%) completed the treatment phase per-protocol (PP); 9 patients discontinued the study due to disease progression (PD) or rapid deterioration. Overall, 110 adverse events were documented (grade 1-2: 80.9%) of which only 10 (9.1%) were drug-related. No drug-related serious adverse event was reported. PBMCs from patients increased cytokine secretion after re-stimulation with standard antigens, confirming an improved cellular immune function. Two patients achieved disease control (PR, SD) after 12 treatment weeks and continued in the extension phase: One patient had PD after 60 weeks, the other remains in sustained partial remission after completion of the EP. Median overall survival (OS) was 24.8 weeks in the ITT population and 115.3 weeks in the PP population. Univariate analysis of pre-treatment characteristics revealed absolute lymphocyte counts, neutrophil to lymphocyte ratios, platelets, MSKCC score, and liver metastasis as putative predictive factors of longer overall survival. Conclusions: MGN1601 administration was safe and showed promising OS in a population of heavily pretreated RCC patients who could receive therapy over 12 weeks (PP population). These results warrant further evaluation in a larger, controlled clinical trial. Baseline biomarkers and factors may allow identifying patients more likely to benefit from this innovative vaccination approach. Clinical trial information: NCT01265368.
Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients (pts) with advanced melanoma (MEL) (CheckMate 067).
Authors: Wolchok Jedd D. , Chiarion-Sileni Vanna , Gonzalez Rene , Rutkowski Piotr , Grob Jean Jacques , Cowey Charles Lance , Lao Christopher D. , Schadendorf Dirk , Ferrucci Pier Francesco , Smylie Michael , Dummer Reinhard , Hill Andrew Graham , Haanen John B. A. G. , Maio Michele , McArthur Grant A. , Yang Arvin , Rollin Linda , Horak Christine E. , Larkin James M. G. , Hodi F. Stephen 
Published: February 2017

LBA1 Background: The results of a phase I study in MEL suggested complementary clinical activity with NIVO (a PD-1 checkpoint inhibitor) plus IPI (a CTLA-4 checkpoint inhibitor). Here, we report the results of a randomized, double-blind, phase III trial designed to evaluate NIVO combined with IPI or NIVO alone vs IPI alone in MEL. Methods: Treatment-naïve pts (N = 945) were randomized 1:1:1 to NIVO 1 mg/kg Q2W + IPI 3 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W, NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo, until progression or unacceptable toxicity. Pts were stratified by PD-L1 status, BRAF mutation status, and M-stage. Co-primary endpoints are progression-free survival (PFS) (reported here) and overall survival (pts continue to be followed). Secondary endpoints include objective response rate (ORR) by RECIST v1.1 and safety. Results: At a minimum follow-up of 9 months, NIVO + IPI and NIVO alone significantly improved PFS and ORR vs IPI (Table). Grade 3-4 drug-related adverse events (AEs) occurred in 55.0%, 16.3%, and 27.3% of pts in the NIVO + IPI, NIVO, and IPI arms, respectively (most commonly diarrhea [9.3%, 2.2%, 6.1%], increased lipase [8.6%, 3.5%, 3.9%], increased alanine aminotransferase [8.3%, 1.3%, 1.6%], and colitis [7.7%, 0.6%, 8.7%]). Drug-related AEs led to discontinuation in 36.4%, 7.7%, and 14.8% of pts in the NIVO + IPI, NIVO, and IPI arms, with 0, 1, and 1 drug-related deaths, respectively. Efficacy outcomes by PD-L1 status will also be presented. Conclusions: NIVO + IPI and NIVO alone had superior clinical activity vs IPI alone. The results with NIVO + IPI and NIVO alone further suggest complementary activity of the two agents. There were no new safety signals or drug-related deaths observed with the combination. Clinical trial information: NCT01844505. [Table: see text]
Primary results, NRG Oncology/NSABP B-35: A clinical trial of anastrozole (A) versus tamoxifen (tam) in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy.
Authors: Margolese Richard G. , Cecchini Reena S. , Julian Thomas B. , Ganz Patricia A. , Costantino Joseph P. , Vallow Laura , Albain Kathy S. , Whitworth Pat W. , Cianfrocca Mary E. , Brufsky Adam , Gross Howard M. , Soori Gamini S. , Hopkins Judith O. , Fehrenbacher Louis , Sturtz Keren , Wozniak Timothy F. , Seay Thomas E. , Mamounas Eleftherios P. , Wolmark Norman 
Published: February 2017

LBA500 Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS. Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (<60 v ≥60). Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women <60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07). Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women <60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP. Clinical trial information: NCT00053898.
Trends in BRCA1/2 mutation testing rates among young women and men with breast cancer, 2005-2012.
Authors: Kehl Kenneth L , Shen Chan , Litton Jennifer Keating , Arun Banu , Giordano Sharon Hermes 
Published: February 2017

103 Background: Guidelines recommend consideration of testing for germline mutations in the BRCA1/2 genes for certain patients with breast cancer, including women diagnosed under age 45 and male patients. However, there are limited data regarding rates of genetic testing in these patients on a population basis. Methods: Using insurance claims from the national MarketScan database of privately insured patients, we identified incident breast cancer cases among women age ≤ 40, women age 41-45, and men of all ages, diagnosed from 2005-2012. We assessed claims for BRCA1/2 testing using Kaplan-Meier analysis and a Cox proportional hazards model, compared across patient cohorts and years of diagnosis. Results: We identified 28,495 patients (11,198 women age ≤ 40, 15,929 women age 41-45, and 1,368 men) for analysis. BRCA1/2 testing rates increased with later years at diagnosis (log-rank P < 0.001 for women age ≤ 40 and women age 41-45; P = 0.01 for men). Men had lower testing rates than women age 41-45, who in turn had lower rates than women age ≤ 40. Furthermore, among women diagnosed in earlier years, testing rates never approached those of patients diagnosed in later years, even after extended follow-up. For example, women age ≤ 40 diagnosed in 2005 had a testing rate by one year after surgery of 19.6% (95% confidence interval, CI, 17.0%-22.5%), and a rate by five years after surgery of 35.3% (95% confidence interval, CI, 31.1%-39.9%). However, for women age ≤ 40 diagnosed in 2009, the testing rate at one year was 57.1% (95% CI, 54.8%-59.5%; hazard ratio for testing, 3.40, 95% CI 2.95-3.92, compared to women age ≤ 40 diagnosed in 2005). Conclusions: Genetic testing rates among men and young women with breast cancer increased with time, but uptake of testing was uneven. Among young women, testing rates for survivors diagnosed in earlier years and followed over time never approached those of patients diagnosed later. These results demonstrate a need to better incorporate genetic counseling into survivorship care, and to promote awareness among providers that long-term breast cancer survivors may be eligible for genetic testing that was not offered or available when they were diagnosed.
Functional subtyping with BluePrint 80-gene profile to identify distinct triple-positive subtypes with and without trastuzumab/chemosensitivity.
Authors: Whitworth Pat W. , Beitsch Peter D. , Rotkis Michael C. , Pellicane James V. , Murray Mary , Baron Paul , Dul Carrie L. , Mislowsky Angela Marie , Nash Charles H. , Richards Paul D. , Lee Laura A. , Stork Lisette , De Snoo Femke , Untch Sarah , Gittleman Mark , Akbari Stephanie , Beatty Jennifer 
Published: February 2017

114 Background: Classification by molecular subtype can aid in the selection of therapy for patients with breast cancer. However at present, the methodology for molecular subtyping is not standardized. The aim of the prospective NBRST study is to compare chemosensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint (BP) functional subtype profile vs. conventional IHC/FISH subtyping. Methods: The study includes women aged 18–90 with histologically proven breast cancer, written informed consent, no excision biopsy or axillary dissection, and no prior therapy for breast cancer. Neo-adjuvant Chemotherapy (NCT) was at the discretion of the physician adhering to NCCN approved or other peer-reviewed regimens. BP in combination with MammaPrint classifies patients into 4 molecular subgroups: Luminal A, Luminal B, HER2 and Basal. Results: 721 patients had definitive surgery. 58/335 (17%) IHC/FISH HR+/HER2- patients were re-classified by BP as Basal (57) or HER2 (1). 92/222 (41%) IHC/FISH HER2+ patients were re-classified as BP Luminal (67) or BP Basal (25). 7/164 (4%) IHC/FISH triple negative (TN) patients were re-classified as BP Luminal (5) or BP HER2 (2). NCT pCR rates were 3% in Luminal A and 9% in Luminal B patients versus 10% pCR in IHC/FISH luminal patients. The NCT pCR rate was 54% in BP HER2 patients. This is significantly superior (p = 0.02) to the pCR rate in IHC/FISH HER2+ patients (40%). BP Basal and IHC/FISH TN had a pCR rate of 35%. Functional BP subtyping divided the 137 IHC/FISH triple positive patients into two major subgroups: BP Luminal (n = 66, pCR = 11%) and BP HER2 (n = 60, pCR = 45%).11 patients were re-classified as BP Basal with pCR = 45%. Conclusions: Molecular subtyping using BP leads to a reclassification of 23% of tumors. The re-classification is most prominent in classically assessed triple positive patients where 48% of patients are re-assigned to the less responsive BP Luminal-type group vs. 44% of patients assigned to the responsive BP HER2-type group. These findings confirm the more accurate identification of molecular subgroups for treatment decision by BluePrint functional subtype classifier. Clinical trial information: NCT01479101.
Tumor profiling of 1189 geriatric breast tumors.
Authors: Xiu Joanne , Reddy Sandeep K. , Pohlmann Paula Raffin 
Published: February 2017

116 Background: Breast cancer (BC) is a disease of aging and the number of geriatric patients is rising in the US. However, this group of patients is often excluded from clinical trials and under-represented in biomarker literature, complicating treatment selection strategies. Methods: BC tumors referred to Caris Life Sciences (Phoenix, AZ) between 2009 and 2015 were tested with a combination of immunohistochemistry (IHC), fluorescent/chromogenic in-situ hybridization (ISH) and sequencing (Next-generation and Sanger). De-identified biomarker data were analyzed. Results: A total of 1189 tumors collected from BC patients (M = 21/F = 1168) aged ≥ 70 (range: 70-97, average 75.6) were analyzed (breast biopsy n = 512; metastatic site n = 677). Of the 1088 tumors with available IHCs of ER, PR and IHC and/or ISH of HER2, 613 (56%) were HR+/HER2-, 72 (7%) were HR+/HER2+, 346 (32%) were TNBC and 57 (5%) were HR-/HER2+. Overall, 39 of 47 genes sequenced carried mutations with frequencies ranging from 0.2% to 37%. Highest mutation rates were seen in PIK3CA (37%), TP53 (37%), BRCA2 (12%), PTEN (5.8%), AKT1 (4.2%), cMET (3.9%), ERBB2 (3.5%), BRCA1 (3.3%) and ATM (3.2%). Among 13 patients with ERBB2 mutation, 3 had it amplified. PD-L1 expression on tumor cells was seen in 13% and PD-1 expression on tumor-infiltrating lymphocytes in 46%, with TNBC subtype showing the highest expression: 20% and 60%, respectively. In addition, TOPO1, TLE3, AR, TOP2A, SPARC were overexpressed in 61%, 58%, 55%, 51%, 37% of tumors, respectively, suggesting potential sensitivity to irinotecan, taxanes, anthracyclines and nab-paclitaxel. TS, RRM1 and ERCC1 were under-expressed in 69%, 69% and 53%, respectively, suggesting potential sensitivity to fluoropyrimidines, gemcitabine and platinums. A comparison with 7531 tumors from patients younger than 70, as well as description of abnormalities per molecular subtype of BC will be presented. Conclusions: Using multiple testing technologies, potentially targetable biomarker aberrations were identified in a large cohort of geriatric tumors. Our study provides key elements for the design of clinical trials focusing on geriatric patient population.
Invasive disease-free survival benefit following neratinib as extended adjuvant therapy in centrally-confirmed HER2+ early-stage breast cancer: The ExteNET phase III randomized placebo-controlled trial.
Authors: Chan Arlene , Martin Miguel , Von Minckwitz Gunter , Ejlertsen Bent , Chia Stephen K. L. , Buyse Marc E. , Mansi Janine , Gnant Michael , Holmes Frankie Ann , Moy Beverly , Iwata Hiroji , Wong Alvin , Lalani Alshad S. , Bryce Richard , Bebchuk Judith D , Delaloge Suzette 
Published: February 2017

117 Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor with clinical efficacy in trastuzumab pre-treated HER2-positive (HER2+) metastatic breast cancer (BC). ExteNET is an ongoing multicenter randomized placebo-controlled phase III trial evaluating the efficacy and safety of a 1-year course of neratinib in patients with early-stage HER2+ BC after trastuzumab-based adjuvant therapy (clinicaltrials.gov: NCT00878709). Methods: Women with locally-confirmed early-stage HER2+ BC were randomly assigned to oral neratinib 240mg/day or matching placebo for 1 year. Archived diagnostic tumor samples were submitted for HER2 gene amplification testing at a central laboratory. Primary endpoint: invasive disease-free survival (iDFS). Secondary endpoints: DFS including ductal carcinoma in situ (DFS+DCIS); distant disease-free survival (DDFS); time to distant recurrence (TDR). Stratified Cox proportional-hazards models were used to estimate hazard ratios (HR) for the ITT and amended ITT (aITT) populations; unstratified models were used for the centrally confirmed HER2 population. Treatment groups were compared using 2-sided log-rank tests. Results: The ITT population included 2840 patients (neratinib, N=1420; placebo, N=1420). The higher-risk aITT population (i.e. node-positive disease and randomized ≤1 year of completing prior trastuzumab) included 1873 patients (neratinib, N=938; placebo, N=935). Of the tumor samples analyzed, 1463 (86%) were centrally confirmed (neratinib, N=741; placebo, N=722). Conclusions: Neratinib significantly improves iDFS in trastuzumab-treated early-stage HER2+ BC patients. An enhanced treatment effect is observed with neratinib in women with centrally confirmed HER2+ tumors. Clinical trial information: NCT00878709. [Table: see text]
Significance of incidentally detected oval, circumscribed enhancing lesions on preoperative breast MRI.
Authors: Lee Jong Yoon , Jang Mi Jung , Kim Sun Mi , Yun Bo La , Jang Ja Yoon 
Published: February 2017

12 Background: To evaluate the characteristics and malignancy rate of oval, circumscribed enhancing lesions seen on preoperative breast MRI in patients with breast cancer. Methods: From January 2010 through May 2013, a total number of 502 oval, circumscribed mass was incidentally found in 326 patients with breast cancer who had undergone preoperative breast MRI. Seventy-eight lesions were excluded due to the lack of follow-up imaging or total mastectomy. Biopsy was performed when suspicious enhancing kinetics or interval change were detected on MRI. Otherwise, MRI or ultrasound follow up for correlated lesion were performed at least 2 years. Clinical and imaging features were recorded for analysis. Results: Of the 424 oval, circumscribed enhancing lesions detected on MRI, twelve (2.8%) were malignant and 412 (97.2%) were benign. There was no significant difference in size between malignant (0.72±0.26 cm) and benign (0.71±0.34 cm) lesions (p = 0.932). Among 424 lesions, 43 lesions (10.1%) were pathologically confirmed and twelve were malignant. Positive predictive value (PPV) of malignancy for the biopsy was 27.9%. Among 12 malignant lesions, 7 (58.3%) were invasive ductal carcinoma, 4 (33.3%) were ductal carcinoma in situ, and 1 (8.3%) was tubular carcinoma. Of the pathologically confirmed benign lesions, 8 (25.8%) were fibroadenoma, 7 (22.6%) were intraductal papilloma. Interestingly, there were significantly frequent MRI features with early fast enhancement and delayed washout pattern in malignant (11/12) compared to benign (29/412) lesions (p < 0.001). PPV of malignancy for early fast enhancement and delayed washout pattern in MRI was 27.5%. Conclusions: Cancer yield in patients with oval, circumscribed enhancing lesion on preoperative breast MRI was 12 (2.8%) of 424. MRI features with early fast enhancement and delayed washout pattern strongly suggested malignancy.