bluuebunny/crossref_metadata_2025_split huggingface dataset:
TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM).
Authors: Freedman Rachel A. , Gelman Rebecca Sue , Melisko Michelle E. , Anders Carey K. , Moy Beverly , Blackwell Kimberly L. , Connolly Roisin M. , Niravath Polly Ann , Van Poznak Catherine H. , Puhalla Shannon , Farooq Sarah , Cropp Anne , Cotter Christine M , Liu Minetta C. , Krop Ian E. , Nangia Julie R. , Tung Nadine M. , Wolff Antonio C. , Winer Eric P. , Lin Nancy U. 
Published: September 2018

1005 Background: Evidence-based treatments (tx) for metastatic, HER2+ BCBM are limited. We previously found a central nervous system (CNS) objective response rate (ORR) of 8% (95% CI 2-22%) for the irreversible, EGFR/HER2-targeted kinase inhibitor, neratinib. To enhance CNS activity, we evaluated the combination of neratinib + capecitabine in a subsequent cohort, and report results here. Methods: Pts with measurable BCBM (≥ 1 cm in longest dimension) and no prior lapatinib or capecitabine were eligible. All but 3 had CNS progression after local CNS tx. During 21 day cycles, pts received capecitabine 750 mg/m2 twice daily x 14 days followed by 7 days off + neratinib 240 mg orally once daily. Loperamide prophylaxis (16 mg total daily) was recommended during cycle 1. Brain MRI and non-CNS imaging were repeated every 2 cycles until 18 wks, then every 3 cycles. The primary endpoint was composite CNS ORR, requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions (central review, VORR), no progression of non-target or non-CNS lesions, no new lesions, no escalating steroids, and no progressive neurologic signs/symptoms. We used a two-stage design with hypotheses ORR 15% and 35% (error rates 5% and 20%), responses in ≥5/19 pts to enter 2ndstage; responses in ≥9/35 [26%] pts to be promising. Results: 39 pts enrolled between 4/2014-11/2016 (2 withdrew before tx, 37 analyzed); median age 51, median prior metastatic lines 2 (range 0-6), 65% had prior WBRT. As of 11/15/16, 23 (62%) patients are alive and 7 remain on protocol tx; median number of cycles initiated = 5 (range 1-26). 18 women (49%) had a VORR (95% CI 32-66%, neurologic exams not yet available on all pts). Overall 12-month survival is 63% (95% CI 43%-77%); 4/7 pts still on protocol therapy have not yet reached 6 cycles. No pts had grade 4 toxicity; 18 (49%) had grade 3 toxicity, with diarrhea most common (32%), and 6 pts discontinued tx for toxicity. Conclusions: The combination of neratinib and capecitabine is active for BCBM with VORR in nearly half of pts, supporting further development of the regimen for BCBM. Updated results will be presented at the meeting. Clinical trial information: NCT01494662.
What do social media-savvy cancer survivors tell us about the completeness of survivorship care plans?
Authors: Radford Diane Mary , Staley Alicia C. , Landercasper Jeffrey , Dietrich Leah L. , Vang Choua A , Borgert Andrew , Attai Deanna J. 
Published: September 2018

10063 Background: The Commission on Cancer (CoC) standard 3.3 became effective in 1/2015 requiring the delivery of a survivorship care plan (SCP) at the completion of curative treatment. Both the CoC and ASCO have recommended minimum requirements for SCPs, which should include both a treatment summary and follow up care plan. Many cancer patients use social media (SM) as a way to obtain support and information. We have shown previously that the majority of SM savvy cancer survivors (88.2%) do not receive SCPs ( J Clin Oncol 35, 2017 suppl 5S; abstr 104). We sought to determine the contents of the SCPs received. Methods: An IRB-approved survey was conducted via the online tool SurveyMonkey from 3/21/2016 to 4/2/2016. Patients were invited to participate via SM outlets reaching cancer-related communities including Twitter chats, Facebook groups, blogs, and targeted emails. Results: A total of 312 patients responded. 63% (194) had completed curative treatment (excluding endocrine therapy). Of these 11.8% (23) reported receiving an SCP at the end of treatment. Of 22 patients who responded, 9/22 (40.9%) found the SCP helpful, 11/22 (50.0%) somewhat helpful, and 2/22 (9.1%) not helpful. The table below shows the components of those SCPs received. Conclusions: Not only did a small percentage of patients receive SCPs but also no patient received a complete SCP per the CoC and ASCO recommendations. Particularly deficient was a description of late/long-term effects of treatment—only 36% received such information. Challenges exist in the delivery of complete SCPs. [Table: see text]
Endocrine and metabolic diseases among colorectal cancer survivors in a population-based cohort.
Authors: Hawkins Makenzie , Soisson Sean Patrick , Blackburn Brenna , Rowe Kerry G. , Deshmukh Vikrant , Newman Michael , Wan Yuan , Fraser Alison M , Smith Ken R , Ulrich Cornelia M , Ganz Patricia A. , Samadder Niloy Jewel , Hashibe Mia 
Published: September 2018

10074 Background: Colorectal cancer is the third most common cancer among men and women in the United States. As of 2016, there were an estimated 1.4 million colorectal cancer survivors. Research on endocrine and metabolic diseases over the long term in colorectal cancer survivors is limited. Obesity is a risk factor for colorectal cancer, thus it is of interest to investigate diseases that may share this risk factor such as diabetes for long term health effects among survivors. Methods: A total of 7,077 colorectal cancer patients who were diagnosed between 1997 to 2012 were identified in the Utah Population Database. A general population cohort of 35,354 individuals was matched on birth year, sex, birth state and follow-up time as a comparison group. Late effects were identified using electronic medical records and statewide ambulatory and inpatient data and were assessed over three time periods of 1-5 years, 5-10 years, and > 10 years. Cox proportional hazard models were used to estimate the risk of late effects after adjusting for matching factors, race, baseline body mass index, and the baseline Charlson Comorbidity Index. Results: Across all three time periods, late effects risk for endocrine diseases and metabolic disorders was significantly greater for colorectal cancer survivors compared to the general population cohort. Risk for diabetes mellitus with complications was significantly increased for survivors and risk was greatest for uncontrolled diabetes (HR = 5.04, 99%CI = 2.38, 10.67) and diabetes with neurological manifestations (HR = 4.10, 99%CI = 2.08, 8.26). Higher risk was also observed for thyroid disorders (HR = 3.09, 99%CI = 2.34, 4.08) and nutritional deficiencies (HR = 4.98, 99%CI = 3.47, 7.17). The risk of obesity in survivors was greatest 1-5 years post cancer diagnosis (HR = 5.04, 99%CI = 2.91, 8.75), but remained significantly increased at all follow-up time periods. Conclusions: Endocrine and metabolic diseases were significantly higher in colorectal cancer survivors across the follow-up periods. As the number of colorectal cancer survivors increases, understanding the long term multimorbidity trajectory is critical for improved survivorship care.
Body weight response with anamorelin in advanced non-small cell lung cancer (NSCLC) patients with anorexia/cachexia: Pooled analysis of two phase III trials.
Authors: Currow David Christopher , Temel Jennifer S. , Abernethy Amy Pickar , Friend John , Giorgino Ruben 
Published: September 2018

10097 Background: Anorexia/cachexia commonly occurs in patients with advanced NSCLC and is associated with increased morbidity and mortality. In two randomized, double-blind, placebo-controlled phase 3 trials in NSCLC patients with cachexia, the ghrelin receptor agonist anamorelin was well tolerated and significantly increased body weight, lean and fat mass, and anorexia/cachexia symptom burden over 12 weeks compared to placebo (Temel J. Lancet Oncol. 2016). Since an involuntary weight loss of ≥ 5% is an established diagnostic criterion for cancer anorexia/cachexia, an analysis was conducted to assess the proportion of patients with ≥ 5% increase in body weight. Methods: NSCLC patients [ROMANA 1 (NCT01387269; N = 484) and ROMANA 2 (NCT01387282; N = 495)] with stage III/IV disease and cachexia (BMI < 20 kg/m2 or ≥ 5% weight loss during prior 6 months) were randomized 2:1 to receive 100 mg once daily oral anamorelin or placebo up to 12 weeks. A pooled analysis was conducted post-hoc in the modified intent-to-treat population (N = 829) to measure the proportion of patients with ≥ 5% increase in body weight at the end of study (or last observation carried forward since week 6 or 9). Results: The percentage of patients with ≥ 5% increase in body weight at the end of study was significantly higher in the anamorelin arm (N = 188/552, 34.1%) compared to placebo (N = 37/277; 13.4%). Among patients with BMI < 20kg/m2 at baseline (N = 182), 47.3% (N = 53/112) of anamorelin patients had a weight increase of ≥ 5% compared to 17.4% (N = 12/69) in the placebo arm. In both cases the nominal p-value was lower than 0.0001. Conclusions: Data from two published large pivotal studies in advanced NSCLC patients with anorexia/cachexia suggest that anamorelin treatment effect size on body weight is clinically relevant, as shown by the higher response rate achieved when the stringent cut-off of ≥ 5% weight gain was applied. The proportion of patients with BMI < 20kg/m2 that benefited from anamorelin treatment was greater than the proportion of patients who benefited in the entire study sample, suggesting that patients with more advanced cachexia may still benefit from anamorelin treatment. Clinical trial information: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.
Clinical application of comprehensive next generation sequencing in the management of metastatic cancer in adults.
Authors: Cobain Erin Frances , Robinson Dan R. , Wu Yi-Mi , Everett Jessica , Rabban Erica , Kumar Chandan , Schuetze Scott , Alva Ajjai Shivaram , Chugh Rashmi , Worden Francis P. , Zalupski Mark , Tomlins Scott A. , Ramnath Nithya , Schott Anne F. , Stoffel Elena Martinez , Smith David C. , Kunju Lakshmi Priya , Hayes Daniel F. , Talpaz Moshe , Chinnaiyan Arul M. 
Published: September 2018

101 Background: Next generation sequencing (NGS) platforms are frequently utilized in the care of patients (pts) with metastatic cancer to identify tumor genomic alterations that may serve as therapeutic targets. Biomarker driven clinical trials, such as NCI-Molecular Analysis for Therapy Choice (MATCH) and Targeted Agent and Profiling Utilization Registry (TAPUR) have augmented clinicians’ ability use this strategy in clinical practice. Methods: From 2011-2015 over 500 adult pts with metastatic solid tumors of diverse lineage underwent biopsy for whole exome and transcriptome sequencing of tumor and matched normal sample through the Michigan Oncology Sequencing Center (Mi-Oncoseq). Genomic alterations identified were reviewed at Precision Medicine Tumor Board and tiered according to their clinical relevance. Alterations were also classified as being identifiable or not identifiable by a commercially available NGS assay such as Oncomine Focus or FoundationOne. Results: Genomic alterations identified by Mi-Oncoseq provided rationale for enrollment in a clinical trial in 72% (n = 360) of cases. The percentage of pts who did receive therapy informed by NGS results increased over time (5% in 2012 versus 11% in 2015). 11% of pts (n = 55) had a pathogenic germline variant (PGV) conferring increased cancer risk identified, none of which were known prior to study entry. Numerous pts had clinically relevant molecular alterations identified by Mi-Oncoseq that would not have been identifiable utilizing targeted NGS assays, including PGVs and activating/deleterious gene fusions. Conclusions: Comprehensive NGS, including DNA and RNA sequencing, readily identifies potentially actionable alterations in the vast majority of pts beyond what is observed with use of targeted NGS platforms. Observed modest increase in utilization of NGS results to direct subsequent therapy over time is due to clinician employment of this strategy earlier in the therapeutic algorithm, increased availability of biomarker driven clinical trials and changes in physician referral patterns. Comprehensive NGS identified many unanticipated PGVs of clinical importance for pts and their families. Clinical trial information: HUM00067928.
A phase II RCT of high-dose vitamin D supplementation for androgen deprivation therapy (ADT)-induced bone loss among older prostate cancer (PCa) patients.
Authors: Peppone Luke Joseph , Mustian Karen Michelle , Peoples Anita Roselyn , Kerns Sarah L. , Reschke Jennifer E , Cole Calvin , Janelsins Michelle Christine , Asare Matthew , Kamen Charles Stewart , Culakova Eva , Zhang Hong , Fung Chunkit , Lin Po-Ju , Mohile Supriya Gupta 
Published: September 2018

10113 Background: ADT is the most commonly used systemic therapy for treating locally advanced and metastatic PCa. ADT use causes hypogonadism, which can result in accelerated bone loss and fragility fractures. Vitamin D (VITD) may protect against bone loss; however it remains unclear if the recommended daily allowance (RDA) of VITD is sufficient to reduce bone loss or whether higher doses are needed. The aim of this phase II RCT was to collect preliminary data on the effect of high-dose VITD on bone mineral density (BMD) in ADT-treated PCa patients compared to the RDA of VITD. Methods: Older PCa patients (≥60 years old) with VITD insufficiency ( < 32 ng/ml), within 6 months of starting ADT and with 6 more planned months of ADT were randomized 1:1 to high-dose VITD (hVITD; 600 IU/daily plus 50,000 IU/weekly) or RDA of VITD (rVITD; 600 IU/daily plus placebo weekly) for 24 weeks. All subjects received 100% of the RDA for calcium (1,000 mg/day). BMD was assessed at the total hip (TH) and lumbar spine (LS) via DXA at pre- and post-intervention. ANCOVA was used to test the change in BMD between groups. Results: 59 PCa patients were accrued (85% white; mean age = 67.6). Serum analyses confirmed high compliance in both groups (25-OH VITD change: hVITD = +32.0 ng/ml vs rVITD = +4.3 ng/ml; p < 0.01). The safety of hVITD was similar to rVITD (Grade I hypercalcemia: hVITD: n = 1 vs rVITD: n = 0). Bone loss was significantly reduced for the hVITD group compared to rVITD group for total hip (TH BMD% change: hVITD = −1.5% vs rVITD = −4.1%; p = 0.02), with a trend for the femoral neck (BMD% change: hVITD = −1.7% vs rVITD = −4.3%; p = 0.06) and trochanter (BMD% change: hVITD = −1.0% vs rVITD = −2.8%; p = 0.10). There was no difference between groups for LS bone loss (LS BMD% change: hVITD = −0.8% vs rVITD = −0.6%; p = 0.75). Conclusions: High-dose VITD supplementation produced significantly greater reductions in hip BMD loss among older PCa patients receiving ADT compared to rVITD. Clinically, higher doses of VITD may be necessary to effectively prevent ADT-induced bone loss. A definitive phase III RCT is needed to confirm these findings. Funding: NCI R21CA175793, K07CA168911 & UG1CA189961. Bio-Tech Pharmacal Inc. supplied all agents. Clinical trial information: NCT02064946.
Multimodal therapy for cancer related fatigue in patients with prostate cancer receiving radiotherapy and androgen deprivation therapy.
Authors: Yennu Sriram , Basen-Engquist Karen , Reed Valerie Klairisa , Carmack Cindy L. , Lee Andrew , Mahmood Usama , Choi Seungtaek , Hess Kenneth R. , Wu Jimin , Williams Janet L. , Lu Zhanni , Cella David , Kuban Deborah A. , Bruera Eduardo 
Published: September 2018

10114 Background: There are limited studies to evaluate treatments that target causative mechanisms of Cancer-related-fatigue (CRF) using validated tools in a defined population. The objective is to determine the feasibility, and the preliminary estimates of the effects of various combinations of standardized exercise, cognitive behavioral therapy (CBT), and methylphenidate (multimodal therapy, or MMT) on CRF as measured by AUC of Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) subscale scores in Pts with prostate cancer receiving radiotherapy with androgen deprivation therapy. Methods: Prostate cancer Pts with CRF scheduled to receive radiotherapy with androgen deprivation therapy were eligible. Using a double blind (patient, investigators) randomized factorial study design, eligible Pts were randomized into 1 of the 8 arms, which included all possible combinations of the interventions (exercise, CBT, and methylphenidate) and/or their corresponding placebo treatments for a duration of 8 weeks. Results: 62/69 (89%) randomized Pts were evaluable. There were no differences in the demographics and baseline fatigue between groups. The adherence rates for pills, exercise and CBT were 96.5%, 67%, and 90% respectively. The study was feasible and there was no significant difference in adverse events by groups. Table 1 shows the comparison of AUC by treatment. For Pts receiving drug compared to placebo, the median FACIT-F AUC was 2328 vs 2095. The drug effect (estimate, 95% CI) in Pts who received Exercise was 596 (68.3, 1125); CBT was 354 (-121, 830); combined Exercise and CBT was -187 (-802,427); and control Exercise, control CBT was 294 (-192,781). Conclusions: Methylphenidate containing combinations were superior to no drug combinations. Methylphenidate + Exercise provided the best signal and should proceed to large randomized control trials. Clinical trial information: NCT01410942. [Table: see text]
Genomic alterations driving breast cancer (BC) metastases and their relationship with the subtype switch in the GEICAM ConvertHER study.
Authors: Albanell Joan , Gonzalez Abel , Gonzalez-Angulo Ana M. , Eterovic Agda Karina , Martinez-De Duenas Eduardo , Zheng Xiaofeng , Guerrero Angel , Liu Shuying , Pérez-Carrión Ramon , Chen Ken , Chacon Jose Ignacio , Mills Gordon B. , Antolín Novoa Silvia , Blancas Isabel , Sanchez-Arago Maria , Carrasco Eva Maria , Caballero Rosalia , Rojo Federico , Meric-Bernstam Funda , Lluch Hernandez Ana 
Published: September 2018

1017 Background: To understand the mechanisms underlying the evolution of tumors in the process of metastasis, we studied 61 paired primary-relapse BC from the GEICAM ConvertHER study. While some of the metastases maintained the clinical (ER/PR and HER2 status) and/or intrinsic subtype (defined by expression arrays) of the original tumor (concordant), others exhibited a subtype shift (discordant). We aimed to identify the genomic alterations driving the metastases and, particularly, their relationship with the subtype switch. Methods: We detected the somatic variants (mutations and copy number alterations (CNAs)) affecting 202 genes across the 61 sample pairs via targeted sequencing. We employed the Cancer Genome Interpreter (cancergenomeinterpreter.org), a bioinformatics approach to identify the alterations most likely driving tumorigenesis, and subsequently identified those whose cancer cell fraction markedly changed in the metastases. We explored the clonal remodeling in metastasis comparing the cell fractions of driver mutations in both concordant and discordant tumors. Results: We found that 156 genes had 747 somatic mutations and 171 genes suffered 1042 somatic CNAs in the 61 studied tumor pairs. We identified a median of 11 and 9 mutations in primaries and metastases, respectively. Several frequent BC mutational drivers, such as TP53, PIK3CA, MLL3, MAP3K1, and NOTCH2 were amongst the more frequently changed their cancer cell fraction in metastases with respect to primaries. We found that driver mutations of discordant tumors exhibited a significantly higher increase of clonal cell fraction. Moreover, whether the clonal status of a driver mutation was conserved in the metastasis was significantly associated to whether the tumor maintains its clinical subtype but not its intrinsic subtype. Conclusions: Our results suggest that a shift in the clinical subtype of BC undergoing metastasis is accompanied by more significant changes at the genomic level than those suffered by tumors that maintain their clinical subtype. This remodeling of the landscape of drivers could open new therapeutic opportunities to specifically target discordant BC.
A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC).
Authors: Metzger Filho Otto , Goel Shom , Barry William Thomas , Hamilton Erika Paige , Tolaney Sara M. , Yardley Denise A. , Rees Rebecca , Demeo Michelle , Mills Caitlin , Hafner Marc , Winer Eric P. , Zhao Jean , Krop Ian E. 
Published: September 2018

1030 Background: PI3K blockade has the potential to revert resistance to anti-HER2 therapies. Methods: Pre-clinical experiments were conducted in parallel to a phase Ib study with the PI3-kinase inhibitor Taselisib + T-DM1 in HER2+ MBC. Results: Pre-clinically, HER2+ cell lines (HCC1954, MDA-MB-361, MDA-MB453) treated with T-DM1 until resistance had decreased HER2 expression. Tx with Taselisib restored HER2 levels in T-DM1 resistant cells. In vivo, the combination of T-DM1 + Taselisib was superior to either agent alone in transgenic mammary carcinomas driven by HER2 with or without a PIK3CA H1047R transgene. The phase Ib study enrolled 26 pts with HER2+ MBC. Median age was 57 (38-95), ER+ (58%), ER- (42%). PIK3CA wild type (35%) mutant (23%) pending results (42%). Pts had a median of 2 lines of prior tx for MBC. Prior T-DM1 was given to 38.5% of pts. Median duration of tx among 18 pts was 4 cycles (2-19). 8 pts remain on tx. No DLTs were observed in the 2 dose levels explored: T-DM1 (3.6mg/Kg) q3 wk with either Taselisib 2mg QD or Taselisib 4mg QD. 20 patients were included in the expansion phase. Most common G3 G4 AEs were thrombocytopenia (19.2%), diarrhea (15.4%), vomiting (7.7%), lipase increase (7.7%) and hyperglycemia (7.7%). Pneumonitis was reported in 4 cases (3 G1, 1 G2); further evaluation revealed elevated beta-glucan in 3 of the 4 cases raising suspicion for pneumocystis pneumonia (PJP). 24/26 pts were evaluable for confirmed response: (4% CR, 29% PR, 50% SD). Confirmed PR/CR according to prior TMD1 (yes 30% no 36%) and PIK3CA mut status (40% mut, 22% wild type; 9/23 PIK3CA results pending). Median PFS was 7.6 mos (95% CI 2.9 to NR). Conclusions: The combination of Taselisib + T-DM1 is superior to either agent alone in mouse models of HER2+ BC. In the phase Ib study, T-DM1 + Taselisib had an acceptable safety profile although PJP prophylaxis should be considered for this regimen. Thrombocytopenia was reversible with no bleeding events. Preliminary evidence of efficacy was observed regardless of PIK3CA status or prior tx with T-DM1. This co-clinical trial allowed for the rapid translation of lab observations to the clinical setting and provided data to facilitate interpretation of the clinical results. Clinical trial information: NCT02390427.