bluuebunny/crossref_metadata_2025_split huggingface dataset:
E-tablets to collect research-quality patient-reported data
Authors: Abernethy A. P. , Herndon J. , Day J. , Hood L. , Wheeler J. , Patwardhan M. B. , Shaw H. S. , Lyerly H. K. 
Published: March 2020

6609 Introduction: Programmed wireless notebook computers (e-tablets) can collect review of systems (ROS) data at point of care. Patients complete surveys in the clinic waiting area; a report is generated for the subsequent clinical visit. Are e-tablets a feasible, acceptable method for collecting data directly from patients in an academic cancer clinic? Can they reliably collect other survey data? Methods: We used PACE e-tablets (SOS, Inc.) to administer Functional Assessment of Cancer Therapy (FACT)-G, FACT-B, MD Anderson Symptom Inventory (MDASI), FACIT-Fatigue, and Self Efficacy instruments, in addition to the PACE Patient Care Monitor (PCM) ROS survey. Participants were 66 breast cancer patients in Duke Breast Cancer Clinic. At 4 visits in 6 months, participants completed all electronic and 1 paper survey. Subscales were compared using paired t-tests. Patients completed an electronic survey of satisfaction with PCM. Results: Mean age, 55 (SD 12); 77% Caucasian; 49% no college degree; 68% married; 61% metastatic cancer. Patients strongly supported e-tablets: easy to read (94%), easy to respond to questions (98%), weight of computer comfortable (87%). Satisfaction increased over time: helpful for reporting symptoms (75–88%), would recommend PCM to other patients (87–94%). 75% indicated PCM helped them remember symptoms to discuss with the clinician. Responses to paper and electronic surveys were nearly identical for 3 of 4 FACT-G, and all FACT-B, MDASI, and FACIT-Fatigue subscales (all p>0.31). Responses on FACT-G Social Wellbeing and 4 Self Efficacy subscales differed from paper to electronic (all p<0.006, all electronic scores poorer). Conclusions: Patients are satisfied with e-tablets. E- tablets furnish comparable data to those collected by paper on nearly all scales tested. PCM offers a valid, feasible method for collecting research-quality, clinically relevant data from patients in outpatient academic oncology. No significant financial relationships to disclose.
Incidence and prevalence of brain metastases among patients with advanced breast cancer in a United States managed-care population
Authors: Pelletier E. M. , Amonkar M. M. , Shim B. 
Published: March 2020

6624 Background: There continues to be uncertainty about the extent of the breast cancer (BC) population afflicted with secondary brain metastases (BM). This study estimated the incidence and prevalence of BM among patients with advanced BC in a US-based population. Methods: Female BC patients diagnosed with secondary BM between 1/2002 and 12/2004 and with a brain or head diagnostic test within 30 days of the BM diagnosis were identified from a nationally representative private payer database (PharMetrics, Inc.). The date of the first BM diagnosis served as the index date. A 1-year look-back period was used to identify patients with a diagnosis of BC and those with and without a history of BM. Patients were required to have continuous health plan enrollment for 1 year prior to and at least 1 month following the index date. Patients aged <18 years, and those aged 65+ and not in a Medicare Risk plan were excluded. The denominator for incidence and prevalence calculations included all patients with diagnosed advanced BC during the study period. A death proxy algorithm was used to estimate the mortality rate. Results: 779 incident and 995 prevalent BM patients were identified; mean age of each cohort was 53 years. In the 1 year prior to the index diagnosis, 73.6% of incident patients were treated with chemotherapy and 25.0% received radiation therapy; <10% of patients had a lumpectomy, mastectomy, or lymph node dissection. About 22% of incident patients died during the follow-up period, an average of 158 days (95% CI=131.1, 183.9) from the index BM diagnosis. From 2002–2004, 8,518 advanced BC patients were identified, resulting in a BM incidence rate of 9.1% (95% CI=8.5%, 9.8%). During this same period, the prevalence of BM was found to be 11.7% (95% CI=11.0%, 12.4%), with rates increasing by year. On average, the first diagnosis of BM occurred 123 days (95% CI=106.9, 139.3) following the BC diagnosis. Conclusions: Secondary BM is a common occurrence among advanced BC patients. The BM incidence rate is in the range (5–20%) of previously published studies. The prevalence of BM was 28% higher than the incidence and increased over time. This increasing frequency suggests an unmet need that could be filled with newer treatments that improve BC outcomes, including the prevention or delay of BM. No significant financial relationships to disclose.
Use of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in chronic phase (CML-CP)
Authors: Atallah E. L. , Kantarjian H. , O'Brien S. , Jones D. , Borthakur G. , Nicaise C. , Cortes J. 
Published: March 2020

7005 Background: Dasatinib (formerly BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL and SRC. Based on its high level of activity in pts with imatinib (im) resistant/intolerant CML-CP, the present phase II trial was designed to study previously untreated CML-CP pts treated with dasatinib. The primary objective was to estimate the proportion of pts attaining major molecular response (BCR-ABL/ABL ratio =0.05% by qPCR) at 12 months (mo). Methods: All pts received dasatinib orally 100 mg/day, and were randomized to either a 50 mg-twice-daily or a 100 mg-once-daily schedule. Dose escalation to 140 mg/day and 180 mg/day for poor response or dose reduction to 80 mg/day and 40 mg/day for toxicity, maintaining the same schedule, was allowed. Results: Of the 31 pts enrolled between 11/05 and 12/06; 52% were female; median age was 41 years (range 18–76). At 3 mo, complete hematologic response (CHR) and major cytogenetic response both occurred in 21 (81%) of 26 evaluable pts and complete cytogenetic response (CCyR) in 19 (73%) pts. After 6 mo of therapy, 20/21 (95%) evaluable pts had achieved CCyR. This compares favorably with a CCyR at 6 mo of 54% with im 400 mg/day and 85% with im 800 mg/day, in historical data of similar patients treated in studies at MD Anderson. At 9 mo, 4/15 (27%) evaluable pts had achieved a major molecular response. The most common non-hematologic adverse events (AE) included dyspnea (8 pts), fatigue (7 pts), muscle pain (6 pts), and headache (5 pts) and were predominantly grade (gr) 1–2. Pleural effusion occurred in only 3 pts (gr 1–2 in all). Grade 3–4 hematologic toxicity (transient) included anemia in 4 pts, neutropenia in 7 pts, and thrombocytopenia in 4 pts. With a median duration of therapy of 10 mo, 13 pts required transient treatment interruption, 9 due to non-hematologic toxicities, 3 due to hematologic toxicities, and 1 due to both. The actual median daily dose for all pts was 100mg. No difference in AEs has been observed between dose schedules. Conclusions: Rapid, complete cytogenetic responses to dasatinib 100 mg/day have been observed in a high percentage of patients with previously untreated CML- CP. Accrual to this trial continues. No significant financial relationships to disclose.
Weekly docetaxel versus docetaxel/gemcitabine in elderly/poor performance status (PS) patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC): Randomized phase III trial of the Minnie Pearl Cancer Research Network
Authors: Greco F. A. , Spigel D. R. , Burris H. A. , Shipley D. L. , Farley C. , Gandhi J. , Houston G. A. , Hainsworth J. D. 
Published: March 2020

7534 Background: Standard treatment for pts with good PS stage IIIB/IV NSCLC currently includes a two-drug platinum-based chemotherapy regimen. Optimum treatment for elderly and/or poor PS pts is less well defined, with some studies showing comparable efficacy/decreased toxicity with single agent treatment. In this randomized phase III trial we compared single agent weekly docetaxel with the combination of docetaxel/gemcitabine. Methods: Between 8/01 and 3/06, 350 pts were enrolled from 39 sites. Eligibility: previously untreated stage IIIB/IV NSCLC; age = 65 years and/or ECOG PS2; measurable disease; no active CNS metastases; adequate kidney, liver, marrow function; informed consent. Pts were randomized to receive docetaxel (36 mg/m2 IV days 1, 8, 15; repeated every 28 days) or docetaxel (30 mg/m2)/gemcitabine (800 mg/m2) both given days 1, 8, 15 of a 28-day cycle. Pts were reevaluated after 8 weeks; responders continued treatment for 6 cycles or until disease progression. Accrual of 330 evaluable pts allowed detection of improvement in 1-year survival from 25% (expected with weekly docetaxel) to 40% (significance level 0.05, power 0.8). Results: Clinical features of pts receiving docetaxel/gemcitabine (n=174) vs. weekly docetaxel (n=171) were similar; 19% were ECOG PS2, and 38% were > 75 years old. After a median follow-up of 22 months, there were no differences between docetaxel/gemcitabine vs weekly docetaxel in median survival (5.6 vs. 5.1 months; p=0.65) or 1-year survival (26% vs. 24%). TTP was prolonged with docetaxel/gemcitabine vs. docetaxel (4.8 months vs. 2.9 months; p=0.0004). Response rates: docetaxel/gemcitabine 25%; docetaxel 17%. Both regimens were well tolerated by most pts; grade 3/4 neutropenia, thrombocytopenia, and anemia were more frequent with docetaxel/gemcitabine. Conclusions: These two regimens have similar efficacy in these elderly/poor PS pts; weekly docetaxel produced less myelosuppression. However, these results in this relatively unselected community-based population emphasize the need for novel treatment approaches. No significant financial relationships to disclose.
A phase II randomized selection trial evaluating concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in patients with advanced non-small cell lung cancer (NSCLC): Final report of SWOG 0342
Authors: Herbst R. S. , Chansky K. , Kelly K. , Atkins J. N. , Davies A. M. , Dakhil S. R. , Albain K. S. , Kim E. S. , Crowley J. J. , Gandara D. R. 
Published: March 2020

7545 Background: Randomized clinical trials have failed to show a survival benefit for small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus chemotherapy in unselected patients with metastatic NSCLC. In contrast, pilot trials of EGFR targeted antibodies plus chemotherapy have suggested enhanced anti-tumor activity. This randomized phase II selection trial was designed to select a cetuximab-chemotherapy regimen for future evaluation in a phase III setting. Methods: Untreated patients (pts) with advanced stage NSCLC were randomized to receive paclitaxel (P) 225 mg/m2 and carboplatin (Cb) AUC=6 every 3 weeks plus concurrent cetuximab (C) 400 mg/m2 loading dose followed by 250 mg/m2, weekly for 4 cycles followed by maintenance C or sequential PCb for 4 cycles followed by C. Treatment was continued until disease progression. Eligible patients were required to have stage IIIB (pleural effusion) or IV (without brain metastases) disease, a performance status of 0–1 and adequate organ function. The primary endpoint was overall survival. The regimen with superior median survival would be considered for further evaluation provided it met a 10-month minimum. Given a true hazard ratio of 1.3, the probability of correctly choosing the superior arm would be > 90%. Results: From July 2004 to June 2005, 242 eligible pts were enrolled onto the study, Final results are described below: Conclusions: Both regimens met efficacy criterion for continued evaluation though the concurrent regimen of PCb + C, had numerically higher survival, and was chosen for further study. Some toxicities were significantly increased with concurrent therapy. A phase II trial of PCb + Cetuximab + Bevacizumab is ongoing (SWOG 0536) in anticipation of a phase III trial. Molecular correlative studies of the EGFR signaling pathway including EGFR IHC, FISH and mutation analysis are underway. No significant financial relationships to disclose. [Table: see text]
A front-line window of opportunity phase II study of sorafenib in patients with advanced non-small cell lung cancer: A North Central Cancer Treatment Group study
Authors: Adjei A. A. , Molina J. R. , Hillman S. L. , Luyun R. F. , Reuter N. F. , Rowland K. M. , Jett J. R. , Mandrekar S. J. , Schild S. E. 
Published: March 2020

7547 Background: Sorafenib is a multikinase inhibitor with single-agent activity in previously treated NSCLC. In an effort to evaluate its single agent activity in previously untreated NSCLC, the NCCTG undertook a front-line “window of opportunity” study. Materials and Methods: Patients with stage IIIB (pleural effusion) or stage IV NSCLC received sorafenib dosed at 400 mg BID continuously, with a cycle defined as 4 weeks. Patients were evaluated weekly during the first 2 cycles with those who progressed rapidly going on to receive standard chemotherapy. Based on a two-stage Fleming design, if only at most 1 confirmed response was observed in the first 20 patients enrolled to stage I, the regimen would be considered ineffective. If 2 or more responses were observed, the study would proceed to stage 2 and accrue an additional 22 patients. If 5 or more confirmed responses were observed, the regimen would be recommended for further testing. Results: The study did not meet the stage I efficacy criteria (only 1 confirmed partial response in the first 20 patients) and was permanently closed after enrolling 25 evaluable patients [15 females, 10 males; 4 stage IIIB, 21 stage IV; median age 67 (45–85)]. 2 patients are still receiving treatment (14 and 15 months). No grade 3 or higher hematologic adverse events were observed. Thirteen (52%) patients had a grade 3 non-hematologic adverse event with fatigue (20%), diarrhea (8%), and dyspnea (8%) being the most common. There was one grade 4 pulmonary hemorrhage. A total of 3 (12%) PRs; and 7 (28%) SD were observed in the 25 patients 7 (28%) patients were progression- free at 24 weeks. Median survival and median time to progression were 8.8 and 2.9 months respectively. Conclusion: While the pre- specified efficacy endpoints were not met, the objective response rate of 12% and median survival of 8.8 months suggest that single agent sorafenib has activity similar to two-drug combinations. The feasibility and utility of the “window of opportunity” design in estimating the activity of novel compounds was demonstrated. Finally, the single-agent activity of sorafenib argues for combination studies with standard chemotherapy agents. No significant financial relationships to disclose.
Toxicity and survival by sex in patients with advanced non-small cell lung carcinoma (NSCLC) on modern Southwest Oncology Group (SWOG) trials
Authors: Albain K. S. , Unger J. , Gotay C. C. , Davies A. M. , Edelman M. , Herbst R. S. , Kelly K. , Williamson S. , Wozniak A. J. , Gandara D. R. 
Published: March 2020

7549 Background: The older lung cancer clinical trial literature suggests that women have better survival than men, possibly due to sex-related changes in drug metabolism based on estrogen levels. A detailed analysis of this issue has not been conducted in the modern chemotherapy era. Thus, the SWOG Lung Committee analyzed outcomes in recent trials, with the hypotheses that either sex-specific toxicity profiles and/or age (as a surrogate for estrogen level) may explain outcome differences. Methods: A data base of eligible patients with complete toxicity data enrolled on 6 consecutive SWOG phase II or III advanced stage NSCLC trials was formed. Treatment was platin-based, plus either gemcitabine, vinorelbine, or a taxane. Toxicities were categorized by type, number and grade with alpha=0.01 (multiple comparisons). Kaplan-Meier survival estimates and Cox multivariate models were computed (alpha=0.05), plus exploratory age by sex interaction analyses. Results: There were1,324 patients (36% women). No difference by sex was found in either maximum toxicity grade, number of toxicities, or specific toxicity types, except for marginally more severe or worse metabolic (12% vs 9%, p=0.02) and life- threatening or worse neurologic (2% vs 1%, p=0.04) toxicities in women. Median, 1- and 2-year survivals were significantly better for women (11 mos, 46%, 19%) vs men (8 mos, 35%, 13%). After adjustment for prognostic factors, women had 14% reduced risk of death (HR 0.86; 95% CI: 0.75, 0.98; p=0.02). The exploratory age by sex cutpoint analysis found women age 60 or older had better survival (11 vs 8 mos, p=0.006), whereas survival was similar by sex for those under age 60. No other age cutpoint was significant. Conclusions: Women with advanced NSCLC survive longer than men after adjustment for other prognostic factors in the modern chemotherapy era. There was no difference in toxicity profile by sex to explain this finding. The survival benefit for women appeared limited to patients age 60 and older, suggesting that estrogen levels may interact with the efficacy of current chemotherapy prescriptions or other as yet undefined factors. This finding, if validated, could be potentially exploited in designing new therapies. No significant financial relationships to disclose.
CALGB 30306: A phase II study of cisplatin (C), irinotecan (I) and bevacizumab (B) for untreated extensive stage small cell lung cancer (ES-SCLC)
Authors: Ready N. , Dudek A. Z. , Wang X. F. , Graziano S. , Green M. R. , Vokes E. E. 
Published: March 2020

7563 Background: VEGF is expressed in 80% of SCLC. Combining chemotherapy with B is effective in advanced non-small cell lung, breast and colon cancers. Methods: This was a phase II study of C 30 mg/m2 and I 65 mg/m2 days 1 and 8 plus B 15 mg/kg day 1 every 21 days for up to 6 cycles in patients with untreated ES-SCLC, PS 0–2, and adequate organ function. Eligibility required no significant bleeding, uncontrolled hypertension, brain mets or other risk factors for B therapy. An initial safety cohort of ten patients was closely followed for unexpected/severe toxicities. Pretreatment blood was collected for biomarker analysis. Statistical design: primary endpoint 12 mo survival rate > 57% (median survival ≥15 mo). Results: 72 pts were enrolled from 3/05–4/06 with one patient deemed ineligible due to diagnosis NSCLC. Demographics: 51% female; median age 62; PS 0–23%, 1–68%, 2–10%. There were no episodes of grade 3 or greater hemoptysis or other primary hemorrhagic episodes. One patient died after an embolic/thrombotic stroke bled secondarily. Other grade 3/4 toxicities included (%): anemia 5, neutropenia 23, platelets 10, hypertension 6, fatigue 12, diarrhea 17, nausea 11, bowel perforation 2, infection 14, all electrolyte 23, stroke 4, vascular access thrombosis 3. Deaths on therapy 3 (4%): pneumonitis 1, stroke 1, heart failure 1. Preliminary efficacy: CR 2 (3%), PR 42 (59%), SD 9 (13%), PD 1 (1%); ORR 62%; ORR excluding unevaluable (4%)/no data (18%): 80%; median progression free survival 7.0 mo (95% C.I. 6.2,8.0); median overall survival 10.6 mo (95% C.I. 8.5, 11.7); median follow-up 9.5 mo. Pretreatment VEGF/PDGF titers have been measured, reported to the CALGB statistics center, and will be analyzed in relation to response and survival outcomes. Conclusions: Although ES-SCLC often has bulky central disease there was no clinically significant hemoptysis. All patients will be at least 12 months from initiation of therapy by 5/07, and mature response and survival data will be presented. No significant financial relationships to disclose.
Phase II study of the efficacy and safety of intravenous (IV) AVE0005 (VEGF Trap) given every 2 weeks in patients (Pts) with platinum- and erlotinib- resistant adenocarcinoma of the lung (NSCLA)
Authors: Massarelli E. , Miller V. A. , Leighl N. B. , Rosen P. J. , Albain K. S. , Hart L. L. , Melnyk O. , Sternas L. , Ackerman J. , Herbst R. S. 
Published: March 2020

7627 Background: AVE0005 (VEGF Trap) is a recombinant fusion molecule of the human VEGF receptor extracellular domains and the Fc portion of human IgG1. Methods: This is an open-label, single arm, multi-center trial employing a Simon 2-stage design. A total of 94 pts are planned. Three responses in the first 37 evaluable pts are required to progress to the second stage. IV AVE0005 (VEGF Trap) 4.0 mg/kg is given every 2 weeks to pts with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Other eligibility requirements include prior treatment with at least two cancer drug regimens in the advanced disease treatment setting, measurable disease, and ECOG performance status (PS) =2. Exclusions include squamous-cell lung cancer, prior treatment with a VEGF or VEGF receptor inhibitor with the exception of bevacizumab, history of brain metastasis, significant bleeding diathesis. End points are objective response rate, safety profile, duration of response, progression-free survival, overall survival and quality of life. Results: The study is ongoing and response and safety data are available for 33 pts (median age=60; males/females=14/19; ECOG PS 0/1/2=6/26/1 pts). A total of 132 cycles have been administered (median=4). Most common reason for withdrawal was progressive disease. Grade 3–4 treatment emergent adverse events (TEAEs) included (pts/percent) dyspnea (5/15%), hypertension and non-cardiac chest pain (3 pts each/9 %) fatigue (2/6 %), and anxiety, epistaxis, nausea, bone pain, proteinuria, febrile neutropenia, pneumonia, pulmonary embolism, and renal pain (1 each/3%). No grade 3 or greater hemoptysis has occurred. Two partial responses (PRs) have been reported to date. Conclusions: AVE0005 (VEGF Trap) 4 mg/kg IV has shown to be generally well tolerated; no significant hemoptysis has been seen to date. Single agent activity has been observed in this heavily treated population; interim futility analysis is awaited. The safety and preliminary activity profile supports further investigation with other targeted agents and cytotoxic chemotherapy. [Table: see text]