bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of erlotinib activity on overall survival in non small cell lung cancer patients: Is the post progression survival a new paradigm?
Authors: Franchina Tindara , Russo Alessandro , Proto Claudia , Chiofalo Giuseppe , Picciotto Maria , Scimone Antonino , Toscano Giuseppe , Berenato Rosa , Noto Laura , Adamo Vincenzo 
Published: March 2020

e19086 Background: In the last few years, the treatment of non-small cell lung cancer (NSCLC) has been dramatically changed with the introduction of EGFR TK (Epidermal Growth Factor Tyrosine Kinase) inhibitors. Given its objectivity and the benefits derived by patients, overall survival (OS) has been historically considered the most important therapeutic objective in advanced NSCLC. However, little is known about postprogression survival (PPS) in NSCLC. This study evaluates the correlation between response to erlotinib and post progression survival (i.e. the time between disease progression and death) to estimate the impact of this drug on overall survival. Methods: We retrospectively analyzed 68 NSCLC unselected patients consecutively treated with second or third line erlotinib at our institution from 2007 to 2010, including in the responder group patients who progressed after stable disease on erlotinib for at least six months (n=20). The relationship between OS and PPS was evaluated by standard statistical tests. P-values <0.05 were considered statistically significant. Results: Survival was significantly prolonged in responders patients (18.6 vs 11.3) suggesting the important role of EGFR TK inhibitors in NSCLC management. In addition a significant increase of PPS was recorded in these patients (9.1 vs 4.6 p=0.02), allowing to perform further therapy lines to better control cancer evolution. Conclusions: These data underline the key role of EGFR in NSCLC growth and progression and the impact of erlotinib in cancer control evolution. Post progression therapy influence the effect on overall survival. This analysis suggests that a treatment strategy incorporating all active agents over the course of disease optimizes OS. Further investigations will be needed in selected patients harboring EGFR-activating mutations to better define the role of PPS as new indicator of erlotinib efficacy.
Bevacizumab in combination with taxane versus non-taxane-containing regimens for advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC): A systematic review.
Authors: Behera Madhusmita , Pillai Rathi Narayana , Owonikoko Taofeek Kunle , Kim Sungjin , Chen Zhengjia , Saba Nabil F. , Belani Chandra Prakash , Khuri Fadlo Raja , Ramalingam Suresh S. 
Published: March 2020

e19094 Background: In pre-clinical studies, the efficacy of anti-angiogenic agents depends on the specific chemotherapy given in combination. This appears to result from abrogation of activated circulating endothelial progenitor cells by cytotoxic agents, with the most favorable results noted with the combination of anti-angiogenic therapy with taxanes. We conducted a systematic review of published clinical trials that evaluated the efficacy of bevacizumab in combination with taxane or non-taxane containing regimens for untreated, non-squamous NSCLC patients. Methods: An extensive search of published clinical trials was conducted from electronic databases (MEDLINE, EMBASE, Cochrane) and meeting proceedings using relevant search criteria. Single arm phase II studies or randomized trials reporting the efficacy of bevacizumab combined with taxane or non-taxane regimens were selected. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2.048) software under the random effect model. Clinical outcome in patients treated with taxane versus non-taxane regimen was compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), and response rate (RR). Results: Twenty-five studies reported between 2005-2013 were eligible. A total of 4,279 patients (1663 and 2616 in the taxane and non-taxane groups respectively) were included. The most common chemotherapy agents used with bevacizumab among non-taxane regimens were gemcitabine (65%), vinorelbine (12%) and pemetrexed (11%). The weighted median age of the population was 59 years (Males-60%; Adenocarcinoma-82%; ECOG performance status 0/1(%)- 39/58). The weighted median OS was 15.1 vs. 13.7 months (p= 0.07); PFS was 7.4 vs. 7.1 months (p=0.27); RR was 39.6% vs. 37.7% (p=0.29) for taxane and non-taxane groups respectively. Conclusions: The combination of bevacizumab with taxane containing regimens is associated with a trend towards improved survival, but not RR and PFS, over non-taxane regimens for first-line therapy of advanced non-squamous NSCLC.
Baseline characteristics from two ongoing phase III trials for the prevention and treatment of muscle wasting in NSCLC.
Authors: Steiner Mitchell S. , Gralla Richard J. , Prado Carla M. M. , Hancock Michael L. , Dalton James T. , Johnston Mary Ann , Crawford Jeffrey 
Published: March 2020

e19100 Background: Although muscle wasting and cancer cachexia occur in > 80% of patients with advanced cancer, few well-powered scientifically-based trials have been conducted. Using enobosarm, a novel SARM, we have now enlisted 650 patients (pts) with advanced NSCLC in two phase III trials. Recent studies indicate major advantages for supportive care in NSCLC at chemotherapy initiation (Temel, NEJM 2010).This presentation examines the feasibility of pt enlistment at chemo initiation, the major characteristics of these pts and trial design for the prevention and treatment of muscle wasting. Methods: Both double-blind, placebo-controlled, international trials evaluate the effect of enobosarm in NSCLC. ˜300 pts with stage III or IV NSCLC were randomized in each trial at initiation of first-line chemo to receive additionally enobosarm or placebo for 5 months. Pts were males and postmenopausal females ≥30 years, ECOG ≤1. First line chemo: a platinum + taxane (Power 1) or platinum + non-taxane (Power 2). Co-primary endpoints at Day 84 are physical function assessed by stair climb power (SCP) and lean body mass (LBM) by DXA. Baseline characteristics are available on 634 pts (98%), as in the Table. Results: See Table. Conclusions: These results indicate that it is feasible to enlist pts receiving first-line chemo in trials designed to prevent or treat muscle wasting and cachexia; their presenting characteristics are typical for NSCLC. Median weight loss at baseline was 5% even though weight loss was not required for study inclusion. LBM and SCP were lower than typically observed in healthy individuals indicating significant functional decline before starting chemo for NSCLC. These phase III trials will determine the effect of enobosarm on preventing and treating muscle wasting in NSCLC. Clinical trial information: NCT01355484 and NCT01355497. [Table: see text]
Exploratory modeling and simulation to support development of motesanib in Asian patients with non-small cell lung cancer (NSCLC) based on MONET1 study results.
Authors: Bruno Rene , Hsu Cheng-Pang , Claret Laurent , Lu Jianfeng , Sun Yu-Nien 
Published: March 2020

e19103 Background: Motesanib failed to improve overall survival (OS) in the MONET1 phase III study when combined to carboplatin/paclitaxel (CP) vs. CP in first-line NSCLC cancer patients (JCO 30:2829-2836, 2011). However, outcome of the study was favorable in a sub-population of Asian patients. We performed exploratory modeling and simulations based on the MONET1 data in order to support further development of motesanib in Asians. Methods: We developed 1) a longitudinal tumor growth inhibition model to estimate time to tumor regrowth (TTG)) using data from 934 out of 1,090 (86%) included in MONET1 and 2) a multivariate parametric model for OS including baseline prognostic factors and tumor size metrics to capture treatment effect. OS model was assessed in simulating OS distribution and hazard ratios (HR) in multiple replicates of MONET1 and comparing 95% predictive distribution (PI) with observed data. Multiple replicates of virtual phase III studies in Asian patients were simulated to assess probability of success of alternative designs. Results: Baseline tumor size (TS) and smoking history (former and current smokers vs. never smokers) were significant independent prognostic factors for OS with Asian ethnicity and log (TTG). Logarithm of OS (in days) was defined by a linear model. Parameter estimates of the OS model are given below (Table). The model successfully predicted OS distributions and HR in the full populations and in Asian patients. Simulations suggested that a 500 patient phase III study would exceed 80% power to demonstrate motesanib combination OS superiority in Asian with an expected HR of 0.74. Conclusions: A model-based estimate of TTG captured treatment effect in Asian and simulations suggested superiority of motesanib combination in these patients. The OS model could be used to simulate expected OS based on longitudinal NSCLC tumor size data with new investigational agents and support development decisions and study design. [Table: see text]
Achieving patient health outcomes via CME: A case-study in educating oncologists in the treatment of non-small cell lung cancer.
Authors: Bregartner Tom 
Published: March 2020

e19104 Background: The Validation Model is an educational series built on the concept of strengthening education by incorporating the patient perspective. After conducting two iterations of the Validation Model to educate oncologists in the treatment of NSCLC, Quintiles Medical Education was able to demonstrate that CME can lead to improved patient health outcomes by changing physician behaviors in practice. Educational measurement tools, including chart audits, revealed an increase in tumor histology and EGFR mutation testing. Histologic and molecular marker testing leads to optimization of treatment based on tumor pathology and genotype, respectively, as per NCCN guidelines. Personalization of treatment according to guidelines results in improved health outcomes. Methods: The Validation Model consisted of 6 educational activities for which efficacy was measured by conducting pre- and post-tests of knowledge and clinical competence among participants. Participants were then asked to complete a follow-up survey which was designed to determine if specific practices had been implemented since participation. The self-self reported behavioral data was validated by the distribution of patient surveys, designed to measure patient satisfaction and expectation with care, and chart audits, designed to determine the actual practice habits of the participating practitioners. Results: More than 500 participants have completed all 6 of the educational activities. The activities have demonstrated improved knowledge and competence in the educational setting and changes to clinical practice and, as a result, patient health outcomes. Conclusions: CME can be used as an effective tool to improve patient health outcomes in the treatment of NSCLC.
Treatment of advanced recurrent NSCLC with daily oral vinorelbine: A phase I trial.
Authors: Tufman Amanda , Borgmeier Astrid , Guetz Sylvia , Von Pawel Joachim , Rittmeyer Achim , Huber Rudolf M. 
Published: March 2020

e19108 Background: Metronomic regimens, in which small, frequent doses of chemotherapy are administered, have been suggested to lower toxicities while maintaining, or even improving, efficacy. The high frequency of administration aims to expose the tumor continuously to the drug, thereby preventing the recovery of malignant cells between cycles. Previous studies have shown that the administration of oral vinorelbine thrice weekly is feasible and well tolerated. We present a phase I dose finding study in which a regimen of daily oral vinorelbine was evaluated in pretreated patients with advanced NSCLC. Methods: Pretreated patients with advanced NSCLC were treated with vinorelbine (Navelbine oral) at fixed daily doses of 20 mg, 30 mg, 40 mg or 50 mg for 21 days of each four-week cycle. The primary end point was the identification of the maximum tolerated dose, which was reached when two out of six patients experienced dose limiting toxicity (DLT) in cycle 1 or 2. Results: 27 patients with advanced NSCLC (78% stage IV, median age 65 y) were enrolled. Most (93%) had received previous systemic therapy (mean: 2.6 lines). Daily administration of oral vinorelbine was well tolerated up to 30 mg/d without any DLT. At 40 mg one of three patients experienced DLT in cycle 1 and another patient in cycle 2. Three out of six patients had DLT at the dose level of 50 mg. Therefore, the recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2 if no DLT had occurred. Eleven patients (2 out of 7 treated with the recommended dose) experienced treatment-related toxicities of grade 3 or higher. The adverse events were primarily hematological (febrile neutropenia: 14.8%, leukopenia: 29.6%, lymphopenia: 18.5%, neutropenia: 18.5%). One patient died as a result of colitis. The frequency of non-hematological toxicities of grade 3 or higher was low with only single cases reported for nausea, fatigue, neutropenic sepsis, pneumonia, increased gamma-glutamyltransferase and anorexia. Conclusions: Daily administration of oral vinorelbine in pretreated patients is feasible and safe. An initial dose of 30mg/d is well tolerated and can be increased to 40mg/d in cycle 2. Further studies are warranted to evaluate the efficacy and safety of this novel approach. Clinical trial information: EudraCT number 2006-001573-25.
Radiotherapy for intubated patients with malignant airway obstruction: Futile, or facilitating extubation?
Authors: Louie Alexander V. , Lane Sophia , Palma David , Warner Andrew , Cao Jeffrey Quoc , Rodrigues George 
Published: March 2020

e19120 Background: There is uncertainty as to the appropriate management of intubated patients with malignant airway obstruction (MAO). Radiotherapy (RT) may be delivered but requires substantial resources in this patient population. In the absence of evidence, it is unknown if radiotherapy facilitates extubation or prolongs ICU stays, resulting in a delay in the appropriate transition to end-of-life care. Methods: We performed a 10-year retrospective review of patients in the ICU treated with RT for MAO. Primary study endpoints were overall survival (OS) and extubation success (ES) defined as ≥48 hours without reintubation or death. Secondary endpoints included rates of discharge from the ICU and to home. Logistic regression and Cox regression analyses were performed to identify factors associated with ES and OS. Results: Twenty-six patients were eligible for analysis. Patients waited an average of 2.9 days (±4.5) from intubation and MV until receiving RT. Seven patients (27%) achieved ES, occurring between days 4 and 22 after RT initiation. All of these patients were discharged from the ICU, and most (n=6) were discharged home. There was a trend for a higher chance of ES in patients who received higher radiation doses (OR per 5 Gy increase: 0.63, p = 0.080). Median OS was only 0.36 months (range 0–113 months), and 6-months OS was 11%. On Cox regression analysis, increased radiation dose was predictive of improved OS (HR per 5 Gy increase: 0.74, p = 0.016). Conclusions: Although median survival is short, in a minority of intubated patients with MAO, RT is associated with ES. Survival beyond six months is uncommon, although improved OS is associated with higher delivered doses of RT.
An assessment of clinical and economic outcomes of U.S. veteran lung cancer patients.
Authors: Fritschel Elyse , Wang Li , Li Lu , Zhang J , Baser Onur 
Published: March 2020

e19122 Background: More people die from lung cancer in the United States than any other cancer type, and despite improvements in survival for other cancer types, 5-year lung cancer survival has remained low (Centers for Disease Control and Prevention. Lung Cancer. Available at www.cdc.gov/cancer/lung. Accessed February 04 , 2013; Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008; 8(3): 819-31.). This study aimed to describe the outcomes of lung cancer patients in the U.S. Department of Veterans Affairs (VA) population. Methods: A retrospective study of patients diagnosed with lung cancer during the study period of October 1, 2005 to September 30, 2010 was conducted using the Veterans Health Administration datasets. Lung cancer patients were identified using International Classification of Disease 9th Revision Clinical Modification (ICD-9-CM) diagnosis code 162.xx. Descriptive statistics were calculated as means ± standard deviation (SD) and percentages. Comorbidities were measured for the 1-year baseline period before the disease identification date. Health care costs and utilization were measured for the 1-year follow-up period after the identification date. Results: In patients identified with lung cancer (n=73,150), common comorbidities included hypertension (n=21,377, 29.22%), chronic airway obstruction (n=14,305, 19.56%), abnormal findings on radiological and other lung field examination (n=12,437, 17.00%), and diabetes (n=11,569, 15.82%). Nearly half of all lung cancer patients had follow-up inpatient visits (46.47%), which translated to an average inpatient cost of $21,420 annually per patient. Nearly every patient studied had at least one follow-up outpatient visit (99.11%), and the average cost per patient totaled $12,986 annually ($12,110 for outpatient office and $411 for outpatient ER service costs). Conclusions: Inpatient and outpatient visits result in considerable health care costs for veteran lung cancer patients. Comorbid conditions are also relatively frequent in this population. Further research could elucidate economic outcomes for lung cancer patients by comorbidity severity.
Less toxic chemotherapy on the uptake of all lines of chemotherapy in advanced non-small cell lung cancer: A 10-year retrospective population-based review.
Authors: Ho Cheryl , Ramsden Katherine , Murray Nevin , Sun Sophie , Melosky Barbara L. , Laskin Janessa J. 
Published: March 2020

e19131 Background: The platinum doublet is standard first-line therapy in advanced NSCLC. Over the past decade, well-tolerated second-line therapies have been approved, including erlotinib and pemetrexed. We hypothesize that the introduction of less-toxic chemotherapy has increased treatment of advanced NSCLC, resulting in improved survival. Methods: The BC Cancer Agency provides cancer care to a population of 4.5 million. A retrospective review was conducted of all referred stage IIIB/IV patients in four 1-yr time cohorts; C1 baseline (1998) and 6 months after the provincial approval of C2 docetaxel (2001), C3 erlotinib (2006) and C4 pemetrexed (2007). Results: 2,623 patients were referred and 720 had systemic therapy. Characteristics: M/F 55%/45%, median age 67 (33-101), ECOG <=1/>=2/unknown 33%/56%/11%, never/former/current/unknown smoker 9%/35%/36%/20%, squam/nonsquam/NOS 18%/41%/41%. More patients received first-line chemotherapy over time; 16%, 23%, 34%, 33% C1-4 respectively. In C1 to C4 uptake of second line (21%, 27%, 38%, 55%) and third line (10%, 10% 14%, 18%) increased. In C1 the most common first-line doublet was cis/vino (70%) and in C4, cis/gem (45%). Second-line doce was frequently used in C2 (51%) but usage decreased in C4 to 7% vs. erlo 50% and pem 26%. In the >=70 group (n=1,118), first-line usage increased from C1 9% to C4 19% and second-line in the C2 (doce) 4% to C4 (erlo+pem avail) 56%. The increased use of systemic therapy was associated with improved survival in all patients: C1 4.56 m vs C4 4.98 m (p=0.004) and treated patients; C1 9.48 m vs C4 12.07 m (p=0.014) and the >= 70 group; C1 9.7 m vs C4 12.5 m (p=0.07). Conclusions: This population-based data set represents the trend of treatments over time in a large geographical area, including community and tertiary care cancer treatment sites. The introduction of less-toxic systemic therapy for advanced NSCLC resulted in an increased proportion of patients treated with first-line chemotherapy and an even greater increase in second-/third-line treatment. This trend was particularly evident in the elderly. Associated with this was a significant improvement in overall survival for all subsets.
Phase Ib extension study of eribulin mesylate in combination with carboplatin in patients with chemotherapy-naive advanced non-small cell lung cancer (NSCLC).
Authors: Raftopoulos Harry , Aisner Joseph , Kumar Kirushna , Goel Sanjay , Dittrich Christian , Jain Minish , Gopalakrishna Prashanth , Salazar Paloma , Jones Beverley , Petrylak Daniel Peter 
Published: March 2020

e19145 Background: Eribulin mesylate as monotherapy has shown antitumor activity in patients with advanced NSCLC that progressed during or after platinum-based doublet chemotherapy (Spira AI et al. Clin Lung Cancer 2012; 13:31-38.). Following evidence of additive activity with eribulin and carboplatin in lung cancer cell lines, a phase Ib, dose-escalation study determined the maximum tolerated dose and optimum administration sequence of the combination as eribulin mesylate 1.1 mg/m2 (0.97 mg/m2 eribulin as free base) followed by carboplatin AUC 6. We report results from an extension arm that investigated the efficacy and safety of this combination in chemo-naïve patients with advanced NSCLC. Methods: Chemo-naïve patients with histologically or cytologically confirmed advanced NSCLC (stage IIIB or IV) with measurable disease were enrolled. Eribulin mesylate was administered intravenously (i.v.) on days 1 and 8 every 21 days, along with carboplatin i.v. on day 1. Efficacy assessments included best overall objective response rate (ORR; RECIST), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR). Adverse events (AEs) were also recorded. Results: 12 patients were accrued (11 male, 1 female) with a median age of 66.5 (range 42-74) years. For the 11 patients evaluable for efficacy, overall ORR was 27.3% (all partial responses) and DCR was 63.6%. Median (range) OS was 12.1 (1.6-12.1) months (5 patients still alive); PFS was 4.2 (0.03+-5.8+) months (upper value censored as 1 patient still responding at final visit); and DOR was 2.9 (2.8-3.1+) months. The most common AEs ≥grade 3 were thrombocytopenia (n=6), neutropenia (n=5), febrile neutropenia (n=4), anemia (n=3), and dyspnea, hypokalemia, leukopenia, and pneumonia (n=2 each). Conclusions: The combination of eribulin and carboplatin yielded no unexpected safety findings. Given the evolving treatment practices for NSCLC, further studies involving larger numbers of patients are warranted, with consideration given to specific histologic subgroups. Clinical trial information: NCT00268905.