bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between clinical characteristics, treatment modality, and outcomes of non-small cell lung cancer
Authors: Yorio J. , Xie Y. , Yan J. , Gerber D. E. 
Published: August 2020

7534 Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death in the United States. NSCLC outcomes vary widely among patients. The degree to which these disparate outcomes reflect differences in treatment modality remains unclear. We therefore examined these associations at a medical center providing care to a diverse patient population. Methods: We performed a retrospective analysis of consecutive patients diagnosed with NSCLC stages I-III from 2000 to 2005 at the University of Texas Southwestern Medical Center. We recorded patient, disease, and treatment characteristics. The association between these characteristics and outcome was assessed using univariate analysis, multivariate logistic regression, and survival analysis. Results: A total of 482 patients met criteria for analysis. Mean age was 64 y, and 52 percent were men. For stage I/II disease, median survival was 6.7 y for patients aged < 65 y vs 4.4 y for age ≥ 65 y (P=0.01); 3.1 y for men vs >5.8 y for women (P=0.0002); 5.6 y for patients with household income below the national median ($41,995) vs 5.6 y for above-median income (P not significant). For stage III, median survival was 1.1 y for age < 65 y vs 0.7 y for age ≥ 65 y (P=0.02); 0.8 y for men vs 1.2 y for women (P=0.02); 0.7 y for below-median income vs 1.2 y for above-median income (P=0.02). Race and hospital setting (public versus private) were not associated with survival. For stage I/II, patients treated with surgery had a median survival of 5.8 y, vs 1.7 y for non-surgical treatment (P<0.0001). For stage III, patients who received surgery and/or radiation had a median survival of 1.2 y vs 0.5 y for other patients (P<0.0001). For stage I/II, treatment modality was associated with hospital setting, race, and income. For stage III, treatment modality was associated with age, gender, hospital setting, race, and income. In multivariate analysis, age (for stage I/II), gender (for stage I/II), and treatment modality (for all stages) were associated with survival. Conclusions: For stages I-III NSCLC, a number of clinical characteristics are associated with outcomes. Differences in treatment modality may account in part for these disparities. These findings warrant further study. No significant financial relationships to disclose.
Phase II pilot study of neoadjuvant docetaxel and cisplatin followed by adjuvant erlotinib in patients with stage I-III non-small cell lung cancer (NSCLC)
Authors: Gold K. A. , Lee J. J. , Rice D. , Tse W. , Stewart D. , Wistuba I. , Herbst R. S. , Lippman S. M. , Hong W. K. , Kim E. S. 
Published: August 2020

7566 Background: Pts with early stage NSCLC, especially with nodal disease, have a poor prognosis despite curative intent therapy. It is unclear which pts may derive the benefit of chemotherapy. The primary endpoint of the study was to assess the tolerability of the regimen. In addition, the clinical response of the chemotherapy regimen as well as tumor biomarkers modulation will be examined. Methods: Pts had previously untreated, potentially surgically resectable, stage I-III NSCLC with ECOG performance status (PS) 0–1 and adequate laboratory parameters. After baseline tissue was obtained, chemotherapy was administered (docetaxel [T] 75 mg/m2 and cisplatin [P] 80 mg/m2 every 3 wks) for 3 cycles. Subsequently, pts underwent restaging, then planned definitive therapy with surgical resection. Pts were then offered treatment for 1 year with erlotinib (E) 150 mg PO daily. Bronchoscopic biopsies were performed at 6 months and 1 year post- surgery. Results: 41 pts were enrolled between 2/07 and 11/08. 3 were not eligible and did not receive treatment. Of the 38 eligible pts: median age was 65 years (42–80); 24 (63.2%) were male; 26 (68%) were PS 1. Stage IB 18% (7), IIB 37% (14), IIIA 39% (15), IIIB 5% (2). 31 pts completed all 3 cycles (35 pts completed at least 2 cycles). 32 pts underwent definitive surgical resection with 1 pt pending for surgery. 5 others did not undergo surgery: pneumonia (1), progressive disease (1), definitive chemo-radiation (3). For pts completing at least 2 cycles of chemotherapy, the radiographic response rate was 57% (20) by RECIST criteria with 40% (14) having stable disease. 1 pt had a complete pathologic response. 16 pts have started adjuvant E, 4 have completed 1 yr of treatment. Grade 3/4 toxicities included neutropenia (6 pts) and hypokalemia (4 pts). Blood and tissue specimens will be analyzed to assess sensitivity to chemotherapy. Conclusions: Neoadjuvant T and P is a tolerable and active regimen with an encouraging response rate in stage I- III resectable NSCLC. In addition to clinical characteristics, determining which patients will benefit from chemotherapy by analyzing their tumor biomarkers may help improve overall outcomes of curative lung cancer pts. Supported by grant DoD# W81XWH-07–1-0306. [Table: see text]
Phase II trial of extrapleural pneumonectomy followed by adjuvant radiotherapy in malignant pleural mesothelioma
Authors: Peigaud C. , Cellerin L. , Roussel J. , Sagan C. , Bordenave S. , Trogrlic S. , Mahé M. , Bennouna J. , Michaud J. , Despins P. 
Published: August 2020

7579 Background: This phase II clinical study was conducted to evaluate the effectiveness of the association of extrapleural pneumonectomy followed by radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). Methods: Eligible patients had histologically proven epithelial or mixed MPM with clinical stage T1–3, N0–2, M0 disease considered to be completely resectable and a WHO performance status of 0 or 1. Surgery had to consist of a complete extrapleural pneumonectomy including resection of pericardium and diaphragm. Postoperative radiotherapy (40 Gy) was delivered through anterior and posterior fields, with a 10 to 20 Gy boost dose if necessary. Results: Thirty seven patients were included in this study. Extrapleural pneumonectomy was completed in 35 patients. Overall hospital mortality was 5,7 %. Major post operative complications were: 3 acute lung injury, 1 bronchopleural fistula, 1 stroke, 1 chylothorax and one diaphragmatic patch dehiscence. IMIG post-operative staging was: stage II = 5 patients; stage III = 25 patients; stage IV = 5 patients. Adjuvant radiation was administered to 29 patients. Survival for the 35 patients with complete resection was 47 ± 8 % at 2 years. Median overall survival time was 22 months. Survival without recurrence was 37 ± 8 % at 2 years. Median time to progression was 15 months. Locoregional recurrence is the most common form of relapse. Conclusions: In the era of surgical neoadjuvant therapy in MPM treatment, extrapleural pneumonectomy followed by radiation therapy in patients with resectable epithelial or mixed MPM can achieve acceptable results. No significant financial relationships to disclose.
Phase II study of NGR-hTNF, a selective vascular targeting agent (VTA), in previously treated patients with malignant pleural mesothelioma (MPM)
Authors: Gregorc V. , Ceresoli G. L. , Zucali P. A. , De Braud F. G. , Bajetta E. , Santoro A. , Viganò M. G. , Caligaris-Cappio F. , Lambiase A. , Bordignon C. 
Published: August 2020

7582 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to an aminopeptidase N (CD13) overexpressed on tumor blood vessels. In preclinical models, NGR-hTNF has shown potent anti-vascular and antitumor activity, both at low and at high doses. Methods: Patients with advanced MPM were treated with a low-dose of NGR-hTNF given intravenously at 0.8 μg/m2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and a total of 27 patients to be enrolled after first and second stage, respectively. Primary endpoint was progression-free survival (PFS) with restaging performed q6w according to MPM-modified RECIST criteria. Results: From May 2007 to January 2008, forty-three patients with radiologically-documented progressive disease after a pemetrexed-based regimen were evaluated over 167 cycles (range, 1 to 17). Patient characteristics were: median age 64 years (range, 54 to 80); male/female 27/16; epithelial/non-epithelial histology 34/9; PS 0/1/2 24/10/9; EORTC score good/poor 34/9. Main grade 1–2 toxicity was chills (71%), transiently occurring after the first infusions. Only one grade 3 treatment-related toxicity was observed. One patient (2%) had a partial response lasting 7.1+ months and 17 patients (40%) maintained stable disease for a median duration of 4.4 months (range, 1.3 to 12.4+ months). The median and 3-month PFS were 2.8 months and 43%, respectively, whereas the median and 1-year overall survival were 11.6 months and 48%, respectively. In an additional 14 patients treated at same dose with a weekly schedule, there was any suggestion of toxicity exacerbation. In this cohort, the PFS rate at 6 months was 36%, with 7 patients (50%) experiencing stable disease for a median duration of 6.9 months (range, 2.4 to 9.3+ months). Conclusions: NGR-hTNF 0.8 μg/m2 weekly is well tolerated, showing prolonged disease control in previously treated MPM patients, and will be further developed in this setting. [Table: see text]
Randomized, double-blind, placebo-controlled phase II study of carboplatin and paclitaxel with or without vorinostat, a histone deacetylase inhibitor (HDAC), for first-line therapy of advanced non-small cell lung cancer (NCI 7863)
Authors: Ramalingam S. S. , Maitland M. , Frankel P. , Argiris A. E. , Koczywas M. , Gitlitz B. , Espinoza-Delgado I. , Vokes E. E. , Gandara D. R. , Belani C. P. 
Published: August 2020

8004 Background: Vorinostat, a HDAC inhibitor, enhances paclitaxel and platinum-mediated anti-cancer activity in preclinical studies by enhanced tubulin acetylation and DNA fragmentation respectively. Promising activity with carboplatin (C), paclitaxel (P), and vorinostat in patients with advanced NSCLC in the phase I study (Ramalingam et al, Clin Cancer Res, 2007) prompted this placebo-controlled, randomized phase II study. Methods: Pts. with stage IIIB (wet) or IV NSCLC, performance status (PS) 0/1, no prior therapy and adequate bone marrow, renal and hepatic function were randomized (2:1) for therapy with PC with either vorinostat or placebo. Treatment consisted of C: AUC=6 mg/ml.min; and P 200 mg/m2 both given on day 3 along with either vorinostat (400 mg PO QD) or placebo on days 1–14 of each 3 wk cycle to a maximum of 6 cycles. The estimated sample size to demonstrate a 50% improvement in response rate for vorinostat over placebo was 93 pts. (one-sided P, type I error 10%). Results: Ninety-four pts. were enrolled (vorinostat-64; placebo-32). Pts. baseline characteristics were similar between the two arms (median age 64, male 60%, PS 0 40%, brain mets 16%). Median # cycles: vorinostat-3.5; placebo - 4. The confirmed response rate was superior with vorinostat over placebo (34% vs. 12.5%, P = 0.02). At the time of analysis, the preliminary median PFS for vorinostat and placebo were 5.75 and 4.1 m respectively (ITT). Follow up for survival is ongoing. Common grade 3/4 toxicities (vorinostat vs. placebo): neutropenia (44% vs. 47%); thrombocytopenia (33% vs. 16%); fatigue (13% vs. 3%); hyponatremia (21% vs. 6%); diarrhea (5% vs. 0). Discontinuation from study after cycle 1 was higher with vorinostat (27% vs. 16%). Biomarker studies on baseline tumor tissue and peripheral blood cells are ongoing. Conclusions: Administration of vorinostat with carboplatin and paclitaxel resulted in a significantly superior response rate for pts.with advanced NSCLC. HDAC inhibition is a novel therapeutic strategy for treatment of NSCLC. Supported by ASCO Career Development Award to S.S.Ramalingam, and NCI NO1-CM-62209, NO1-CM-62201, NO1-CM-62208. [Table: see text]
Molecular and clinical predictors of outcome for cetuximab in non-small cell lung cancer (NSCLC): Data from the FLEX study
Authors: O'Byrne K. J. , Bondarenko I. , Barrios C. , Eschbach C. , Martens U. , Hotko Y. , Kortsik C. , Celik I. , Stroh C. , Pirker R. 
Published: August 2020

8007 Background: The multinational, randomized, phase III FLEX study compared cisplatin/vinorelbine (CT) plus the EGFR- antibody, cetuximab (Erbitux), with CT alone in the 1st-line treatment of patients (pts) with advanced EGFR-expressing NSCLC and demonstrated a statistically significant OS benefit for the cetuximab combination. We hypothesized that KRAS mutation status is predictive for cetuximab efficacy and enables optimal use of cetuximab. The relationship between early-onset acne-like rash (ie rash that developed ≤21 days of treatment initiation) and OS time of pts treated with CT and cetuximab was also evaluated. Methods: Archived tumor samples from 554/1125 pts were available. Genomic DNA derived from formalin-fixed paraffin embedded tumor tissue was analyzed for KRAS using an LNA-mediated qPCR clamping assay capable of detecting oncogenic mutations at codons 12 and 13. The Kaplan-Meier method was used to estimate OS time and PFS time in pts with KRAS wild-type (wt) and mutant (mt) tumors for each treatment arm. All pts treated with cisplatin/vinorelbine plus cetuximab who were alive at 21 days were included in a landmark analysis evaluating the relationship between early-onset acne-like rash and OS time. Results: KRAS results were obtained from 379 pts. A KRAS mutation was detected in 72 (19%) pts. The comparison of the cetuximab treatment effects in pts with KRAS wt tumors and pts with KRAS mt tumors showed no marked differences with regard to OS or PFS. A total of 518 pts were included in the landmark analysis. Pts treated with cetuximab who developed early acne-like rash of any grade (grade 1–3; 56%, n=290) had a longer median OS than those without acne-like rash (n=228) (median [95% CI]: 15.0 months [12.8–16.4] vs 8.8 months [7.6–11.1]; HR [95% CI]: 0.63 [0.52–0.77]; p<0.001). Analysis of EGFR FISH is ongoing and results will be presented. Conclusions: Clinical data from the FLEX study do not support the hypothesis that KRAS mutation status is predictive for cetuximab efficacy when combined with 1st- line chemotherapy in advanced NSCLC, whereas early acne-like rash of any grade appears to be associated with better outcome in pts treated with platinum-based chemotherapy plus cetuximab in this setting. [Table: see text]
Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST)
Authors: Natale R. B. , Thongprasert S. , Greco F. A. , Thomas M. , Tsai C. M. , Sunpaweravong P. , Ferry D. , Langmuir P. , Rowbottom J. A. , Goss G. D. 
Published: August 2020

8009 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This phase III study compared the efficacy of vandetanib vs erlotinib in patients (pts) with advanced, previously treated NSCLC. Methods: Eligible pts (stage IIIB/IV NSCLC, PS 0–2, 1–2 prior chemotherapies; all histologies permitted) were randomized 1:1 to receive vandetanib 300 mg/day or erlotinib 150 mg/day until progression/toxicity. The primary objective was to show superiority in progression-free survival (PFS) for vandetanib vs erlotinib. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS; EORTC QoL Questionnaire) and safety. Results: Between Oct 06-Nov 07, 1240 pts (mean age 61 yrs; 38% female; 22% squamous) were randomized to receive vandetanib (n=623) or erlotinib (n=617). Baseline characteristics were similar in both arms. Median duration of follow-up was 14 months, with 88% pts progressed and 67% dead. There was no difference in PFS for pts treated with vandetanib vs erlotinib (hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721), and no difference in the secondary endpoints of OS (HR 1.01, 95.08% CI 0.89–1.16; P=0.830), ORR (both 12%) and TDS (pain: HR 0.92, P=0.289; dyspnea: HR 1.07, P=0.407; cough: HR 0.94, P=0.455). A preplanned non-inferiority analysis for PFS and OS demonstrated equivalent efficacy for vandetanib and erlotinib. The adverse events (AEs) observed for vandetanib were generally consistent with previous NSCLC studies with vandetanib 300 mg. There was a higher incidence of some AEs (any grade) with vandetanib vs erlotinib, including diarrhea (50% vs 38%) and hypertension (16% vs 2%); rash was more frequent with erlotinib (38% vs 28%). The overall incidence of CTCAE grade ≥3 AEs was also higher with vandetanib (50% vs 40%). The incidence of protocol-defined QTc prolongation in the vandetanib arm was 5%. Conclusions: The study did not meet its primary objective of demonstrating PFS prolongation with vandetanib vs erlotinib in pts with previously treated advanced NSCLC. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a preplanned non-inferiority analysis. [Table: see text]
S0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC): A SWOG phase II study
Authors: Gandara D. , Kim E. S. , Herbst R. S. , Moon J. , Redman M. W. , Dakhil S. R. , Hirsch F. , Mack P. C. , Franklin W. , Kelly K. 
Published: August 2020

8015 Background: Cetuximab (CX) plus platinum-based chemotherapy improves overall survival (OS) in advanced NSCLC (FLEX). SWOG previously showed that EGFR FISH is associated with efficacy outcomes in patients (pts) receiving CB/P/CX (S0342). Bevacizumab (B) plus chemotherapy also increases survival (E4599) in eligible pts. Given the biologic rationale for combining EGFR and VEGFR targeted agents, S0536 investigated the safety and efficacy of carboplatin (CB), paclitaxel (P) and CX plus B. Methods: Eligibility: treatment-naïve advanced stage non-squamous cell NSCLC, no requirement for EGFR positivity, PS 0–1, no brain metastases or hemoptysis. Treatment: CB AUC 6, P 200 mg/m2, B 15 mg/kg IV day 1 every 3 weeks, CX 400 mg/m2 day 1 then 250 mg/m2 weekly for up to 6 cycles; then B 15 mg/kg every 3 weeks and CX 250 mg/m2 weekly until progression. Primary endpoint: feasibility defined by the frequency and severity of ≥grade 4 hemorrhagic toxicities. Secondary endpoints: response rate, progression-free survival (PFS), OS and toxicity. Results: 110 pts enrolled from August 2006 to September 2007; 104 assessable. Pt characteristics: median age 64 years (42–78), Male/Female 52/52, PS 0/1 43/61, stage IIIB/IV 9/95, adenocarcinoma: 81, current/former smoker: 82. Overall toxicities were acceptable and comparable to S0342 and E4599. Primary endpoint was met: grade ≥4 hemorrhage: 2% (95% CI: 0–7%). There were 4 treatment-related deaths: lung hemorrhage (2), infection (1), unknown (1). Partial response (PR): 51/95 assessable (54%; 43%-64%); Stable disease (SD): 22/95 (23%). Disease control rate (PR+SD): 77%. With median follow up of 15 months (mos), PFS is 7 mos (18 pts remain progression-free) and OS is 14 mos. 1 year survival is 57% (47–67%). EGFR IHC by H score (>0 vs 0) showed a nonsignificant trend toward improved survival: 15 vs 11 mos (p=0.14). Conclusions: CB/P, CX plus B demonstrates safety, tolerability and efficacy in advanced NSCLC and is the most active regimen studied to date in SWOG. Additional S0536 biomarker studies including EGFR FISH will be presented. S0819, a Phase III trial of CB/P ± CX (plus B in eligible pts) is under development and is designed to validate EGFR FISH as a predictive biomarker. [Table: see text]
First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: A phase III study (002) by North East Japan Gefitinib Study Group
Authors: Kobayashi K. , Inoue A. , Maemondo M. , Sugawara S. , Isobe H. , Oizumi S. , Saijo Y. , Gemma A. , Morita S. , Hagiwara K. , Nukiwa T. 
Published: August 2020

8016 Background: Based on our promising results of phase II studies estimating gefitinib in NSCLC pts with sensitive EGFR mutations (JCO 2006, BJC 2006), this multicenter phase III trial compared progression free survival (PFS) of first line gefitinib versus first line chemotherapy in EGFR mutation positive pts with stage IIIB/IV NSCLC. Per protocol, an analysis for safety except response, PFS and overall survival were estimated. Methods: PNA-LNA PCR clamp test, which had been developed and validated by us (Cancer Res 2005, Cancer Sci 2007), was employed to detect EGFR mutations using cytological samples or histological samples. Pts having sensitive EGFR mutations, measurable site(s), ECOG PS 0–1, age of 20–75 years, and no prior chemotherapy were randomized (1:1 ratio; balanced for institution, sex, and stage) to receive Arm A: gefitinb (250 mg/ day) orally, or Arms B: CBDCA AUC 6 and TXL 200mg/m2 in 21-day cycles until disease progression. The primary endpoint was PFS, and the sample size was calculated to be 320 in total (alpha=5%, power=80%) to confirm the superiority of Arm A (hazard ratio = 0.69). Results: From April 2006 to July 2008, 155 pts were enrolled (Arm A=80; Arm B=75). Their characteristics were well balanced between arms: median age=65 years; 64% female; 77% Stage IV; 93% adenocarcinoma, 61% non-smoker. There were several differences in toxicities between Arm A and Arm B (grade 4 neutropenia: 1% vs. 29%, grade 3–4 liver dysfunction: 24% vs. 1%, grade 3 neuropathy: 0% vs. 5%, respectively, p<0.01). But these were tolerable in both arms. Furthermore, there were no interstitial lung disease and no toxic deaths in both arms. Analyzing both arms together, preliminary response rate and PFS of the 155 pts were 53.7% and 6.5 mos, respectively. Conclusions: This is the first prospective study to compare first line gefitinib with first line chemotherapy for advanced NSCLC pts harboring EGFR mutations. Due to acceptable toxicities, the independent safety committee decided to continue this study further. At the end of 2008, 200 pts have been entered to this study, and, per protocol, an interim analysis to investigate PFS will be performed in May 2009. No significant financial relationships to disclose.