Jaqueline Willemann Rogerio

Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis

Abstract Objective: To examine the outcomes following resection of subependymal giant cell astrocytoma (SEGA) among patients with SEGA-associated tuberous sclerosis complex (TSC). Methods: Using three large US national healthcare claims databases, we retrospectively examined the outcomes of SEGA surgery among TSC patients who underwent SEGA surgery between 2000 and 2009. The examined outcomes were: prevalence rates of post-surgery SEGA, repeated SEGA surgery, and postoperative complications (surgical procedure complications, nervous system complications, postoperative infections, complications of subdural empyemas, and complications of epidural abscesses). Descriptive data analysis and two-sided one sample t-test for mean or proportion were used to assess the characteristics of patients and the outcomes of SEGA surgery. Results: The selected patients (N = 47) had a mean age of 11.6 years at their first SEGA surgery and 66% were male. During the third through twelfth months following surgery, 34% had post-surgery SEGA (diagnosis) and 12% underwent repeated SEGA surgeries. During the first post-surgery year, 48.9% of patients developed postoperative complications (34.0% had complications relating to the surgical procedure, 12.8% had nervous system complications, 6.4% developed postoperative infections, 17.0% had complications of subdural empyemas, and 2.1% had complications of epidural abscesses). Conclusions: SEGA surgery was associated with statistically significant risks of developing post-surgery SEGA, requiring repeated SEGA surgery and developing postoperative complications. Future efforts in reducing these outcomes, either through improving surgical procedures or through alternative treatments, are urgently needed. Limitations: This study has its limitation in data source representativeness and measurement accuracy.

Patients rank toxicity against progression free survival in second-line treatment of advanced renal cell carcinoma

Abstract Background: The aims of this study were to quantify and contrast patient preferences between second-line advanced renal cell carcinoma (RCC) medication profiles and their associated benefits and toxicities, and to help frame the doctor–patient discussion about selecting appropriate RCC therapies. Research design and methods: Adult residents of the US with a diagnosis of RCC completed a Web-enabled choice-format conjoint survey consisting of a series of 10 treatment-choice questions, each of which included a pair of hypothetical RCC medication profiles. Each profile was described by various medication attributes (features or outcomes) with varying levels. The attributes included efficacy (progression-free survival [PFS]), tolerability (fatigue, stomach problems, mucositis or stomatitis, hand–foot syndrome [HFS]), serious but rare adverse events (pneumonitis, hepatic impairment), and mode of administration. Treatment-choice questions were based on an experimental design with known statistical properties. Random-parameters logit regression was used to estimate relative preference weights for each attribute level. Benefit equivalent measures (additional months of PFS in exchange for toxicities) were also calculated. Results: Of the 272 patients who completed the survey, the majority were female (53%), white (92%), and had at least a college degree (66%). The mean age was 57 years (standard deviation: 10 years). Over the range of attributes and attribute levels included in the survey, PFS was the most important attribute, followed by fatigue, stomach problems, hepatic impairment, mucositis or stomatitis, HFS, pneumonitis, and mode of administration. To reduce severe fatigue to mild-to-moderate fatigue, patients on average would be willing to forego 4.4 months of PFS. To reduce hepatic impairment risk from 0.5% to 0.0%, patients on average would be willing to forego 1.0 month of PFS. The main study limitation was that patients answered hypothetical treatment-choice questions. Conclusions: This study provides information to physicians about patient priorities when reviewing and selecting RCC therapies with patients.

Surgical resection of subependymal giant cell astrocytomas (SEGAs) and changes in SEGA-related conditions: a US national claims database study

Abstract Objectives: To compare the prevalence rates of clinical conditions related to subependymal giant cell astrocytomas (SEGAs) before and after SEGA surgery among patients with tuberous sclerosis complex (TSC). Methods: Based on three US national claims databases, we analyzed and compared the prevalence rates of 21 SEGA-related conditions (including seizures, hydrocephalus, headaches and stroke or hemiparesis) in the six months preceding surgery with the rates in the second through sixth post-surgery months and in the seventh through twelfth post-surgery months among TSC patients who underwent SEGA surgery during 2000–2009. Repeated measures analysis with a bootstrapping method was used to assess the surgery impact. Results: Patients (N = 47) had a mean age of 11.5 years at their first SEGA surgery, and 66% were male. Compared with the six months preceding surgery, the post-surgery prevalence rates increased by 23–26% for seizures, 21–26% for hydrocephalus, 17–19% for headache and 6–9% for stroke or hemiparesis (all p < 0.05). Repeated measures analysis confirmed the impact of surgery on the prevalence rate of these five conditions (all p < 0.05). Conclusions: SEGA surgery has its important role in SEGA treatment. However, after SEGA surgery this group of TSC patients had increased prevalence rates of seizures, hydrocephalus, vision disorders, headaches, stroke or hemiparesis, and autism. Future research to examine the causes of these symptoms is imperative. Limitations: The study results have limitations in data source representativeness, coding accuracy, and study design.

Healthcare Resource Use and Expenditures among Metastatic Breast Cancer Patients Treated with HER2-Targeted Agents

Objective. To compare healthcare utilization (HCU) and costs of women newly diagnosed with metastatic breast cancer (mBC) by receipt of HER2-targeted agents (H2T) and among H2T subgroups. Methods. Adult women newly diagnosed with mBC (index date) during 2008–2012 were followed until enrollment end or inpatient death. Study cohorts were antineoplastic ± H2Ts, and no treatment; and subgroups of H2T patients stratified by receipt of hormonal therapy (HT+/HT−), by de novo versus recurrent disease status, and by age group. All-cause (ALL) and breast cancer related (BCR) HCU and costs (in 2012 dollars) were estimated using a generalized linear model. Results. Of 18,059 women, 14.6% were H2T users 71.1% nonusers, and 14.3% untreated. No treatment patients had the highest ALL and BCR inpatient HCU, and ALL emergency room HCU. H2Ts users had the highest ALL and BCR office visits, lab and diagnostic radiology, radiation treatments, other outpatient services, and prescription antineoplastics. Adjusted ALL and BCR costs were the highest for H2T users and, in H2T subgroups, higher for HT—versus HT+ and de novo versus recurrent, and declined with older age. Conclusions. Receipt of H2Ts was associated with greater levels of ALL and BCR HCU and costs. H2T subgroups of HT−, de novo, and younger age had higher HCU and costs, possibly indicating more aggressive treatments.

Treatment patterns and survival in metastatic breast cancer patients by tumor characteristics

Abstract Objectives: Study objectives were to compare the treatment patterns and clinical outcomes among metastatic breast cancer (mBC) patients by receipt of HER2-targeted agents and among subgroups of HER2-targeted agent users. Research design and methods: Adult women newly diagnosed with mBC (index date) during 2008–2012 were selected from the Truven MarketScan databases and followed until end of enrollment or inpatient death. Patients with <12 months of data, pre-index primary cancers other than breast cancer, pregnancy, or HIV/AIDS were excluded. Study cohorts were users and nonusers of HER2-targeted agents and women with no treatment; and HER2-targeted agent subgroups by receipt of hormonal therapy (HT), de novo vs. recurrent status, and age group. Pre- and post-index breast cancer treatments were compared across cohorts. Relative risk of progression and death were evaluated among the subset of patients with mortality data. Results: Of 18,059 eligible women selected, 14.6% were users of HER2-targeted agents, 71.1% were nonusers, and 14.3% untreated. HER2-targeted agent users received more aggressive cancer treatments compared to nonusers. HER2-targeted agent users were 33% more likely to progress and had a similar risk of death compared to nonusers. Among HER2-targeted agent subgroups, the risk of progression was 30% lower among HT+ patients vs. HT-, 32% lower for de novo vs. recurrent, and similar across age groups. The risk of death was 52% lower for HT+ vs. HT−, 35% lower for de novo vs. recurrent, and increased with age. Limitations: Identification of distant metastasis, tumor receptor expression and disease progression were based on claims data rather than on clinical assessment. Conclusions: Receipt of HER2-targeted agents (vs. non-HER2-targeted agents) was significantly associated with receipt of pre- and post-index breast cancer treatments. HER2-targeted agent users were more likely to progress but had a similar risk of death during follow-up. Among HER2-targeted agent subgroups, HT+ and de novo status were associated with a reduced risk of progression and death.

Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer: Sequencing of chemotherapy and endocrine therapy.

164 Background: National Comprehensive Cancer Network breast cancer guidelines suggest sequencing of systemic therapy. This study examined sequencing of endocrine and chemotherapy treatments to better understand real-world treatment patterns for HR+/HER2- advanced breast cancer. METHODS A proprietary clinical cancer database with physician-reported clinical data on patients with breast cancer was linked to medical and pharmacy claims (2008-2012) from a national US health plan. Study patients had HR+ and HER2- status. Advanced cancer cohorts were defined: stage III (SIII) or IV (SIV) at initial diagnosis, or developed metastases following initial diagnosis (MET). Index date was the first date of advanced cancer diagnosis or date of metastases following initial diagnosis. Health plan enrollment for 3 months pre- and ≥ 3-months post- index date was required; patients who died within 3 months after index date and were continuously enrolled were retained. A 3-month baseline period assessed prior treatment; a variable follow-up (until disenrollment or 31 Oct 2012) assessed patterns of endocrine and chemotherapy treatments following index date. RESULTS A total of 954 breast cancer patients met study inclusion criteria and were HR+/HER2- with ≥ 3 months of continuous enrollment after index date, with 369 of the 954 (38.68%) SIII, 117 (12.26%) SIV, and 469 (49.16%) MET patients. In the study population, 83.65% were treated with endocrine therapy, starting an average of 179 days after index date. A total of 80.29% were treated with chemotherapy, starting an average of 53 days following the index date; 65% of patients initiated chemotherapy after index date without prior endocrine treatment. Rates varied by cohort: 90% of SIII, 57% of SIV, and 48% of MET patients had no evidence of endocrine treatment prior to initiating chemotherapy. CONCLUSIONS This study found large proportions of HR+/HER2- advanced breast cancer patients initiated chemotherapy without prior endocrine therapy. Further investigation of patient characteristics and outcomes by therapy sequencing patterns will help illuminate the extent to which patterns adhere to NCCN guidelines.

Treatment characteristics and mortality of a large insured female population with advanced or metastatic breast cancer by receipt of HER2-targeted agents

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Comparative Effectiveness Research 2015:5 35–47 Comparative Effectiveness Research Dovepress

Abstract P3-06-14: Serum activin A and response to the aromatase inhibibitor (AI) letrozole versus tamoxifen in metastatic breast cancer

Introduction: The prognostic and predictive utility of pretreatment serum activin A (TGF-B superfamily ligand) was correlated with the response of first-line metastatic breast cancer patients (MBC) in the phase 3 randomized trial of letrozole vs. tamoxifen. Methods: 555 ER+ first-line MBC patients had pretreatment serum available for activin A ELISA (RD p In the total population with available serum (n=555), multivariate analysis for TTP revealed that high serum activin A was a significant adverse prognostic factor (HR=1.46, p Conclusions: Patients with high pretreatment serum activin A levels had a significantly reduced ORR, CBR, TTP and OS compared to patients with low serum activin A. The results were similar within the letrozole or tamoxifen treatment arms, and within the serum HER2 not-elevated subgroups. High pretreatment serum activin A level is associated with relative resistance to hormone therapy in first-line metastatic breast cancer. Citation Format: Meghan Jensen, Ashley Kang, Suhail M Ali, Kim Leitzel, Ashwani Garg, Jaqueline Rogerio, David Chen, Raymond Hall, Scott Hofsess, Hilary A Chaudri-Ross, Nicholas Bade, Walter P Carney, Allan Lipton. Serum activin A and response to the aromatase inhibibitor (AI) letrozole versus tamoxifen in metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-14.

Abstract LB-194: Window of opportunity preoperative interrogation of mTOR pathway in patients with resectable non-small cell lung cancer (NSCLC).

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: We conducted this ‘window- of-opportunity’ study to characterize the biologic activity of everolimus, an allosteric inhibitor of mTOR pathway, in patients with surgically resectable NSCLC. Methods: Patients with surgically resectable NSCLC (Stage I-III) underwent baseline tumor biopsy and FDG PET/CT scan followed by treatment with everolimus (5 or 10mg daily for up to 28 days). A repeat PET/CT scan was obtained 24 hours prior to surgery. Blood samples for pharmacokinetic (PK) assay for drug levels were collected at 0.5, 1, 2, 5, 8 and 24 hours post drug ingestion on Days 1, 8 and 21. Control patients not treated with everolimus also had paired FDG PET/CT scans prior to surgery. Target modulation by everolimus was assessed in vivo by PET and ex vivo by immunohistochemical detection of total and phosphorylated mTOR, Akt, S6, eIF4e and 4EBP1 in pretreatment and posttreatment tissue samples. Alterations in common driver mutations in NSCLC were assessed using SnapShot minisequencing technique. Results: We enrolled 33 patients; 23 on everolimus and 10 on the control arm. Median age: 64 yrs (range 36-77), gender: (14/19 -M/F), stage (I - 14; II - 13; IIIA - 6); histology (adenocarcinoma - 22; squamous - 7; others - 4). Treatment was tolerated well with mostly grade 1/2 toxicities (hyperglycemia, hypertriglyceridemia, anemia and fatigue) and 32 of 33 patients proceeded with surgery on schedule. Compared to controls, there was significant reduction in SUVmax and median anatomic tumor size in a dose-dependent manner in everolimus-treated patients (15.38 vs. -21.74 vs. -23.23; p=0.012 and 4.39 vs. 0 vs.-13.33; p=0.039 in the control, 5mg and 10mg cohorts respectively). There was a similar trend in reduced metabolic activity in Ras mutant tumors treated with 10mg everolimus compared to control (88% vs. -28%). Comparison of baseline biopsy samples and resected tumor specimens in control and everolimus-treated patients showed reduction of S6 (-27.38 vs. 0 vs. -78.95; p=0.0536), pS6 (-20 vs. -29.17 vs. -57.14; p=0.0233) and p4EBP1 (-45.83 vs. 0 vs. -75; p=0.057) with greatest reduction observed in patients treated with higher dose of everolimus. Conclusions: Everolimus exerts a measurable, dose-dependent biologic activity in NSCLC tumors. ‘Window of opportunity’ studies in early stage NSCLC provide strong mechanistic insights and guide development of novel targeted agents. Acknowledgements: This study was supported by NCI grant P01 CA116676. Everolimus was provided by Novartis Oncology. TKO, GS, SS, SSR and FRK are Georgia Cancer Coalition Distinguished Cancer Scholars. Citation Format: Taofeek Kunle Owonikoko, Daniel L. Miller, Seth Force, Gabriel Sica, Scott Kono, Madhusmita Behera, Jennifer Mendel, Zhengjia Chen, Allan Pickens, Robert W. Fu, William F. Auffermann, Jaqueline Rogerio, William E. Torres, Haian Fu, John Hohneker, Shi-Yong Sun, Anthony A. Gal, Suresh S. Ramalingam, Fadlo R. Khuri. Window of opportunity preoperative interrogation of mTOR pathway in patients with resectable non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-194. doi:10.1158/1538-7445.AM2013-LB-194

Abstract P4-12-04: Initial treatment and survival among elderly breast cancer patients by receipt of human epidermal growth factor receptor 2-targeted therapy: An analysis of US national data 2006-2009

BACKGROUND: There are few studies of initial treatment and survival among elderly, newly diagnosed breast cancer (BC) patients stratified by receipt of human epidermal growth factor receptor 2- (HER2-) targeted therapy. METHODS: Using linked Surveillance, Epidemiology, and End Results (SEER) and Medicare claims and enrollment data from 2006-2009, women aged 65+ years with an incident diagnosis of BC (index date) in 2007 and no prior history of any other cancer were identified and followed to evaluate initial treatment and survival. Study patients were required to have continuous enrollment from 1 year before index (baseline period) through the end of the data window, disenrollment or death, whichever came first. Patients were classified as having received HER2-targeted therapy if they had any claim indicating trastuzumab or lapatinib following diagnosis. Demographics, initial treatment (within 4 months of diagnosis), and survival (proportion of patients who died during the study period) were evaluated by receipt of HER2-targeted therapy (and by age and stage among those who received HER2-targeted therapy). Kaplan-Meier (KM) survival curves and survival at 36 months were estimated by stage. Treatment included surgery, radiation, chemotherapy, biologic, and hormone therapy, and was evaluated among patients with > 2 months of follow-up. RESULTS: Among 11,238 female BC patients, 510 received HER2-targeted therapy (99.8% trastuzumab, 2.5% lapatinib) and 10,728 did not. Those who received HER2-targeted therapy were slightly younger at diagnosis (mean age 73 vs. 76, P CONCLUSIONS: Elderly, newly diagnosed BC patients who received HER2-targeted therapy were younger than those who did not received HER2-targeted therapy. Initial treatment patterns varied between the two groups, but survival outcomes were similar. Among patients in the HER2-targeted therapy group, treatment characteristics also differed by disease stage and age. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-04.