bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erlotinib in non-small cell lung cancer (NSCLC): Interim safety analysis of the TRUST study
Authors: Gatzemeier U. , Ardizzoni A. , Horwood K. , van Meerbeeck J. , Magyar P. , Gottfried M. , Arrieta O. , Krzakowski M. , Franke F. , van Zandwijk N. 
Published: March 2020

7645 Background: In patients (pts) with relapsed NSCLC, erlotinib 150 mg/d significantly prolonged survival, delayed symptom progression, and improved quality of life versus placebo (Shepherd et al, N Engl J Med 2005;353:123–32). TRUST is an open label, non- randomized trial initiated to provide erlotinib access to pts with advanced NSCLC. Methods: Eligible pts had stage IIIb/IV NSCLC, and had failed or were unsuitable for chemotherapy. Erlotinib (150 mg/d p.o.) was given until disease progression or unacceptable toxicity. Pts were monitored monthly. Results: In November 2006, data were available for 5,015 pts (ITT population) from 51 countries. Median age was 63y (range 19–95). Pt characteristics (%) were: male/female 62/38; Caucasian/Oriental/other 76/19/5; non-smoker/ex- or current-smoker 28/71 (no data 1); ECOG PS 0/1/2/3 21/53/20/6; adenocarcinoma/squamous cell/other 53/25/21; stage IIIb/IV 22/78; erlotinib 1st/2nd/3rd-line/other 14/48/37/1. Safety data were available for 4,423 pts, 55% of whom had at least one adverse event (AE). Only 5% had one or more erlotinib- related serious AEs, the most common being gastrointestinal (GI) disorders (86 pts; 63 grade [gr] 3/4). 6% of pts discontinued treatment due to erlotinib-related AEs: GI disorders in 96 pts (54 gr 3/4), skin disorders in 92 (50 gr 3/4). Unexpected erlotinib-related AEs occurred in 10% of pts (4% gr 1, 3% gr 2, 3% gr 3/4). As expected, rash was observed in 70% of pts, with the majority (84%) being of gr 1/2. 80% pts received >4 weeks of erlotinib. Among 4,405 pts, only 14% had dose reductions, mainly due to rash (83%) and diarrhea (21%). Similar safety results were seen for 2nd-line pts only. Efficacy for all and 2nd-line pts will be presented. Conclusions: These results, achieved through routine clinical use of erlotinib in unselected pts with advanced NSCLC, confirm the favorable tolerability profile seen with erlotinib in selected patients in the clinical trial setting. [Table: see text]
Prediction of distant relapse risk in stage I-II non-small cell lung cancer (NSCLC) by gene expression profiling
Authors: Jassem J. , Jarzab M. , Niklinski J. , Rzyman W. , Kowalska M. , Oczko-Wojciechowska M. , Kobierska-Gulida G. , Chyczewski L. , Szostakiewicz B. , Jarzab B. 
Published: March 2020

7657 Background: Our aim was to determine the genes predictive for relapse-free and overall survival in stage I-II NSCLC. Methods: We analyzed the gene expression profiles in lung cancer specimens collected from 70 NSCLC patients (pts) who underwent curative pulmonary resection between 1999 and 2004 in two Polish centers (Gdansk, Bialystok). There were 54 men and 16 women aged 37–77 yrs (median 62.5 yrs), 45 with squamous cell ca, 22 with adenoca and 3 with large cell ca. Eight pts were staged pT1, 59 pT2 and 3 pT3; there were 49 and 21 pN0 and pN1 pts, respectively. 30 pts had a relapse and 32 pts died (median follow-up 36 months). Samples of tumor tissue were collected intraoperatively and snap-frozen, total RNA was isolated and gene expression profiling was carried out by Affymetrix HG-U133 2.0 Plus oligonucleotide microarray. Samples were pre-processed with RMA algorithm, gene selection was carried out by Support Vector Machines and Bayesian Compound Covariate Classifier, using own procedures and BRB-Array software developed by Simon and Peng Lam. Survival time prediction was carried out by method developed by Bair and Tibshirani (PLoS Biology 2004). Results: Based on the microarray gene expression profiling, the relapse could be predicted with 75.0% specificity and 53.3% sensitivity (positive predictive value [PPV] 61.5%, negative predictive value [NPV] 68.2%). The classifier, obtained by cross-validation of 70-sample dataset, consisted of 170 transcripts. Further gene selection was based on the prediction of the relapse-free survival: 1,919 genes, selected by fitting Cox proportional hazard model (p<0.05) and further used to predict survival by 4 principal components, distinguished between pts with high and low risk of relapse (p<0.05, log-rank test). The prediction of death was possible with 66.7% specificity and 57.1% sensitivity (PPV 53.3%, NPV 70%), but the distinction between high- and low-risk pts was significantly weaker than based on lymph node involvement (N0 vs. N1). Thus, for the final selection of genes this clinical variable was incorporated into the model as a covariate. Conclusions: Prediction of the risk of relapse in stage I-II NSCLC based on the gene expression profile is feasible, with NPV of 68.2%. No significant financial relationships to disclose.
Predictive significance of bone sialoprotein and osteopontin for bone metastases in respectable non-small cell lung cancer: A retrospective study
Authors: Zhang L. , Hou X. , Rao H. , Hou J. , Luo R. , Huang H. , Huang P. 
Published: March 2020

7666 Background: Bone sialoprotein (BSP) and osteopontin (OPN) have been demonstrated predictive of bone metastases in breast and prostate carcinoma, consistent with the proposed role of BSP as a stimulator of bone mineralization and OPN in differentiation and activation of osteoclasts. Bone metastasis (BM) is often developed in non-small-cell lung cancer (NSCLC), but no predictive biomarker was identified for high risk of metastatic bone dissemination. Methods: 180 completely resected NSCLC patients were included in this study. 38 patients subsequently developed BM. Paraffin embedded primary tumor tissue of patients were supplied to produce a tissue microarray, and immunohistochemistry method was used for evaluation the expression of BSP and OPN. Different expressions of these two biomarkers among BM group and non-BM group were estimated by χ2 test. Bone metastasis-free survival was analyzed by Kaplan-Meier method. The prognostic impact of clinicopathologic parameters and biomarker expression was evaluated by Cox propotional hazards model. Results: BSP expression was associated with BM (P=0.027), while OPN expression could not reach statistical significance (P=0.495). Univariate analysis demonstrated that expression of BSP (P=0.036), N stage (P=0.000) and clinical stage (P=0.001) were associated with time interval to BM. Multivariate analyses showed BSP expression (RR=1.779, P=0.012) and clinical stage (RR=1.620, P=0.005) were independent prognostic factors for BM. Conclusions: BSP protein expression in the primary resected NSCLC is strongly associated with BM and could be used to identify high-risk patients. Correlation of OPN protein expression and bone metastasis need further investigation. No significant financial relationships to disclose.
Biomarker analysis from TRUST, a trial of erlotinib in non-small cell lung cancer (NSCLC)
Authors: Schneider C. , Schott-von Römer K. , Gütz S. , Raack B. , Dierkesmann R. , Laack E. , Guschall W. , Schmittel A. , Gatzemeier U. 
Published: March 2020

7674 Background: The EGFR tyrosine kinase inhibitor erlotinib significantly prolonged survival and improved QoL in relapsed NSCLC patients (pts) (Shepherd et al. NEJM 2005;353:123). TRUST is an ongoing, single arm, international, multicenter trial providing erlotinib access to pts with advanced NSCLC (>6,500 enrolled). Methods: Stage IIIb/IV NSCLC; failed (1–2 regimens) or unsuitable for chemotherapy. Pts received erlotinib 150 mg/day p.o. until progression or unacceptable toxicity. Pts were assessed for response, progression free survival (PFS), overall survival (OS) and safety. Where possible, tumor tissue samples were collected from German centers and centrally assessed by; immunohistochemistry (IHC; EGFR, pMAPK), fluorescence in-situ hybridization (FISH; EGFR gene copy number), and DNA sequencing (EGFR, KRAS gene mutations). Results were assessed for correlations with treatment benefit. Results: Nov 2006, biomarker data were available for 287 of 393 German pts; median age 65 yrs (range 33–90). Baseline characteristics (%): male/female (59/41); Caucasian/Oriental/no data (99/1/<1); non-smoker/former or current smoker (25/75); adenocarcinoma/squamous cell/BAC/large cell/other/no data (57/33/3/2/1/4). 40% received erlotinib 2nd line. Of 230 pts with response data, 7.4% had a complete or partial response. Median PFS was 11.0 weeks (95% CI: 9.0–13.1). Preliminary analyses showed EGFR IHC+ (=10% staining; 223/278) pts (vs EGFR IHC-) had longer OS (HR=0.75; p=0.1) and PFS (HR=0.71; p=0.03). OS (HR=0.53; p=0.02) and PFS (HR=0.38; p=0.0001) were significantly prolonged in EGFR FISH+ (28/133) vs FISH- pts. Pts with KRAS mutations (17/107) had shorter OS (HR=1.5; p=0.18) and PFS (HR=1.6; p=0.08) vs wildtype. pMAPK+ status (29/108) was associated with shorter OS (HR=2.6; p<0.0001) and PFS (HR=1.6; p=0.0007). Conclusion: As TRUST is a single arm study, conclusions on the prognostic or predictive significance of these biomarkers cannot be drawn. Erlotinib treated NSCLC pts with EGFR IHC+, EGFR FISH+ or pMAPK- tumors may have better outcomes than those with EGFR IHC-, EGFR FISH-, and pMAPK+ tumors, but to prospectively assess the predictive value of these biomarkers, a randomized phase III study is ongoing (BO18192, SATURN). [Table: see text]
Induction 3D-chemoradiation (CRT) yields a high rate of pathologic complete response in stage IIB(Pancoast)/III NSCLC operable patients (pts) without increasing perioperative mortality after (bi-)lobectomy: A review of 107 cases treated in a community- based center
Authors: Pourel N. , Hilgers W. , Santelmo N. , Naffaa N. , Reboul F. 
Published: March 2020

7704 Background: Optimal preoperative treatment for stage IIB/III NSCLC remains a subject of controversy. According to the results of INT0139 trial (Albain KS et al in Proc ASCO 2005, abstr #7014), induction CRT appears to be superior to chemotherapy alone (CT) in terms of pathologic complete response (or microscopic residual foci, pCR), but increases postoperative (postop) mortality after pneumonectomy. Methods: Pts were selected through a multidisciplinary committee according to functional and resecability criteria. Induction treatment comprised 45 Gy/25 fractions/5 weeks. RT delivered to the primary tumor and pathologic hilar and/or mediastinal nodes (CTV) with an extra-margin of 1 to 1.5 cm (PTV). A 3D 5-field technique was used for all patients with 8–25 MV photons. Concurrent CT regimen was Cisplatinum 20 mg/m2 and Etoposide 50 mg/m2 (PE), d1–5, d29–33. Surgery was performed 4 to 6 weeks after CRT completion in deemed resectable pts. Inoperable pts were referred for a 20 Gy boost ± 1 extra-cycle of PE. Results: From 1996 to 2005, 107 NSCLC pts received CRT (stage IIB-Pancoast 18, IIIA 58 and IIIB 31). One hundred pts received the whole 45 Gy+PEx2; 72 pts had a thoracotomy (pneumonectomy 21, lobectomy 45, bi-lobectomy 5, exploratory only 1). During the 3-month postop time, 5 pts (6.9%) died, 4 after pneumonectomy (R 3, L 1, 19%), 1 after lobectomy (2.2%); 34 pts had 1–3 significant complication(s) (mainly, arrhythmia 10, pneumonia 8 (lethal 1), prolonged air leak 7, fistula 4, empyema 4 (lethal 2), pulmonary embolism 3 (lethal 2)).A pCR was observed in 39.5% of 71 resected pts; mediastinal nodes were sterilized in 60.9% of 46 cN2 pts. Analysis of survival and predictive factors is ongoing. Conclusions: Surgery is feasible after induction chemo-RT, particularly (bi-)lobectomy, in stage IIB/III NSCLC pts but pneumonectomy carries an inacceptable risk of postop death (particularly, right pneumonectomy). CRT yields an encouraging pCR rate of 39.5%. No significant financial relationships to disclose.
Pemetrexed (P) in relapsed small cell lung cancer (SCLC): Preliminary results of a phase II trial
Authors: Raju R. N. , Neubauer M. A. , Smith D. A. , Richards D. A. , Asmar L. , Cunneen J. L. , Chen R. , Tai D. F. , Obasaju C. K. , Socinski M. A. 
Published: March 2020

7716 Background: Pts with relapsed SCLC have a poor prognosis and few effective treatment options. P is a novel multitargeted antifolate that is active and well-tolerated as a single agent in lung cancer. We undertook a trial to assess the efficacy and safety of single- agent P in both chemosensitive (S) and chemorefractory (R) relapsed SCLC pts. Methods: Eligible pts had limited or extensive- stage SCLC, PS 0 to 2, and only 1 prior chemo regimen. S pts were defined as having had a prior response with disease progression >2 mos from end of 1st-line chemo. R pts were those who progressed while on 1st-line therapy, or had any response but progression <2 mos from end of 1st-line chemo. The initial P dose tested was 500 mg/m2 q 21 d. Planned sample sizes were 36 S pts in a 2-stage sequential fashion with potential early stopping for lack of efficacy or unacceptable toxicity, and 25 R pts in a single-stage design with no stopping rule. The stopping rule was invoked when <3 of 14 qualified S pts responded. The protocol was then amended to evaluate P at 900 mg/m2 in additional cohorts of 40 S and 40 R pts. Pts were to receive folic acid and Vitamin B12 prior to treatment with P. The primary outcome measure was response rate. Results: From 7/04 to 3/06, 121 pts were enrolled, with 116 pts treated. S and R pts were analyzed separately at both dose levels. S pts (n=56): M/F, 29/27; median age 65 (range 43–82); PS 0/1/2, 25/23/8. R pts (n=65): M/F, 31/34; median age 64 (range, 35–85); PS 0/1/2, 16/37/12. *3 S pts treated with P 900 mg/m2 remain with disease control after a minimum of 11 mos of follow-up. Conclusions: Preliminary clinical benefit rates (CR+PR+SD) of 20% and 17.4% achieved respectively in S and R pts treated with P 500 mg/m2 suggest modest activity of single-agent P in relapsed SCLC. P can be given at a dose of 900 mg/m2 without a significant increase in Grades 3–4 toxicities, although this does not appear to increase efficacy. [Table: see text] [Table: see text]
The progress of small cell lung cancer management using irinotecan plus cisplatin chemotherapy
Authors: Lee J. S. , Han J. , Yu S. , Yoon S. , Lim E. , Pyo H. , Kim H. , Lee D. , Kim H. , Cho K. , Lee G. 
Published: March 2020

7721 Background: Etoposide/cisplatin (EP) is the most widely used regimen resulting in a median survival of 8–10 mos and 17–20 mos respectively for patients (pts) with extensive-disease (ED) and limited-disease (LD). Encouraged by a phase III trial result that showed better survival outcome after Irinotecan/cisplatin (IP) combination as compared with EP, we previously reported promising activity of IP regimen for LD-SCLC and also for ED-SCLC. To further evaluate the role of IP in SCLC pts, we conducted two additional phase II studies. Methods: Between May 2003 and June 2006, a total of 196 SCLC pts (ED: 120, LD: 76) were enrolled in two separate trials. All pts were chemo-naive and ECOG PS of 0–2. Pts with ED-SCLC received irinotecan 60 mg/m2 intravenously (IV) and cisplatin 30 mg/m2 IV on days 1 and 8 every 21 days for 8 cycles followed by 6 cycles of irinotecan maintenance or observation. Treatment for LD-SCLC consisted of two 28-day cycles of cisplatin 30 mg/m2 IV on days 1 and 8 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15, followed by two 21-day cycles of cisplatin 60 mg/m2 IV on day 1, plus etoposide 100 mg/m2 IV on days 1 to 3 with concurrent twice-daily thoracic radiation of total 45 Gy. Hoping to modify the treatment-related toxicity, 36 pts were given epoietin and 20 were given amifostine while 15 received neither during the concurrent chemo-radiation therapy. Results: For ED- SCLC, overall response rate was 92.6% with CR rate of 11.1%. The median survival was 13.8 mos (95% CI, 12.2 to15.3) with 1-and 2-year survival rates of 58.6% and 18.9%. The median progression-free survival (PFS) was 7.3 mos with 1-and 2-year PFS rates of 18.1% and 5.4%. Irinotecan maintenance did not affect the outcome, however. For LD-SCLC, the response rate was 97.1% with CR rate of 44.9%. The median survival was 24.9 mos (95% CI, 18.5 to 31.3) with 1-and 2-year survival rates of 75.2% and 51.4%. The median PFS was 11.0 mos (95% CI, 7.8–14.2) with 1-year PFS rates of 46.8%. The most common toxicity associated with IP treatment was grade 3 or 4 neutropenia (64.6% for ED, 45.3% for LD). Grade 3 diarrhea was developed in 12.4% for ED and 4% for LD pts. Conclusion: Significant antitumor activity of IP chemotherapy as shown suggests further progress in SCLC therapy. No significant financial relationships to disclose.
CHOP-R + bortezomib as initial therapy for diffuse large B-cell lymphoma (DLBCL)
Authors: Leonard J. P. , Furman R. R. , Cheung Y. K. , Vose J. M. , Glynn P. W. , Ruan J. , Martin P. , Niesvizky R. , LaCasce A. , Chadburn A. , Coleman M. 
Published: March 2020

8031 Background: Bortezomib is a proteasome inhibitor with anti-tumor activity in B cell malignancies. These effects, which may relate to NF-kappaB associated pathways, could sensitize tumor cells to standard chemotherapy-based regimens and enhance efficacy. We report findings of a phase I/II trial of dose-escalated bortezomib + standard CHOP-rituximab in DLBCL patients (accrual of the MCL cohort of this study remains ongoing). Methods: Patients with previously untreated DLBCL (n=40) received CHOP-21 + rituximab (375 mg/m2 each cycle) plus bortezomib at 0.7 mg/m2 (Arm 0, n=4), 1.0 mg/m2 (Arm 1, n=8) or 1.3 mg/m2 (Arm 2, n=28 including phase I and all phase II) on days 1 and 4 of each cycle Results: Median age (n=40) was 58 years (range 21–86), thirty-five subjects (88%) had stage III/IV disease at study entry, and 29 (73%) had elevated serum lactate dehydrogenase (LDH). Patients generally had unfavorable baseline international prognostic index (IPI) scores of 2 in 16 subjects (40%) and 3–5 in 19 subjects (48%). Median follow-up is 21 months (range 9 - 35 months). Treatment was generally well tolerated. Peripheral neuropathy occurred in 22 subjects (55%), with 45% grade 1, 5% grade 2 and 5% grade 3. Grade 4 hematologic toxicity included thrombocytopenia (15%) and leukopenia (15%). Four subjects (3 over age 75 and all with high risk IPI) died prior to first response assessment. Intent to treat (ITT) overall response rate (n=40) is 90% with 68% CR/CRu. For the evaluable subset (n=36), ORR was 100% with CR/CRu 75%. Kaplan-Meier estimate (n=40) of 2-year progression-free survival is 72%. Of all 19 enrolled (ITT) patients in the high-intermediate or high-risk IPI groups, 14 (74%) were alive without progression at last assessment. Correlation of outcome with cell of origin type (activated B cell vs germinal center) is ongoing. Conclusions: Bortezomib can be administered with acceptable toxicity in conjunction with CHOP-R chemotherapy. Efficacy findings with this combination regimen in newly-diagnosed DLBCL are encouraging and warrant further study. No significant financial relationships to disclose.
Low doses of humanized anti-CD20 antibody, IMMU-106 (hA20), in refractory or recurrent NHL: Phase I/II results
Authors: Morschhauser F. , Leonard J. P. , Fayad L. , Coiffier B. , Petillon M. , Coleman M. , Horne H. , Teoh N. , Wegener W. A. , Goldenberg D. M. 
Published: March 2020

8032 Background: An open-label, multicenter study has shown that the humanized anti-CD20 antibody, IMMU-106 (hA20), which has framework regions of epratuzumab, has a good safety and efficacy profile in NHL pts when administered once-weekly × 4 at different doses. The trial is now focused on confirming the efficacy of lower doses (80–120 mg/m2/wk × 4). Methods: A total of 68 pts (35 male, 33 female; age 34–84) received hA20 at 750 (N=3), 375 (N=27), 200 (N=11), 120 (N=21), or 80 mg/m2 (N=6). They had follicular (FL, N=47) or other (N=21) B-cell NHL, were predominantly stage III/IV (N=47) at study entry, and had received 1–8 prior treatments (median, 2), including 1 (N=40) or more (N=21) rituximab regimens (without progression within 6 months). Results: Sixty- six pts completed all 4 infusions; 1 pt progressed during treatment and withdrew, while another pt with hives and chills after prior rituximab discontinued treatment after a similar episode at 1st infusion. hA20 was generally well tolerated, with shorter infusion times (typically 2 h initially and 1 h subsequently) at lower doses. Drug-related adverse events were transient, Grade 1–2, most occurring only at 1st infusion, and there was no evidence of HAHA in 54 pts now evaluated. Mean antibody serum levels increased with dose and infusions; serum clearance at 375 mg/m2 appears similar to rituximab. Currently, 48 pts with at least 12 wks follow-up were evaluated by Cheson criteria: 32 FL pts had 15 (47%) OR's with 7 (22%) CR/CRu's, even after 2–4 prior rituximab-regimens, and 17 non-FL pts had 6 (38%) OR's, with 1 CRu in a marginal zone NHL pt. At a median follow-up of 11 mo., 9/21 pts with ORs are continuing responses, including 4 long-lived responses (15–20 mo). The evaluated pts include 17 pts at 120 mg/m2 who had 5 (29%) ORs with 3 (17%) CR/CRu's. Responses at 80 mg/m2 remain to be evaluated, but B-cell depletion occurs after the 1st infusion even at this low dose. Conclusions: hA20 appears well-tolerated, with no evidence of significant adverse events other than minor infusion reactions, even at short infusion times. B-cell depletion and responses have occurred at all doses evaluated, with no clear-cut evidence of a dose-response. As such, the study is continuing to confirm the efficacy of lower doses. No significant financial relationships to disclose.
Efficacy and toxicity of dose-adjusted EPOCH-rituximab in adults with newly diagnosed Burkitt lymphoma
Authors: Dunleavy K. , Healey Bird B. R. , Pittaluga S. , Grant N. , Shovlin M. , Little R. , Yarchoan R. , Steinberg S. , Jaffe E. S. , Janik J. , Wilson W. H. 
Published: March 2020

8035 Background: Burkitt Lymphoma (BL) is a rare and highly aggressive lymphoma, characterized by a high tumor proliferation rate. While the standard therapy of BL is highly effective, it involves intensive, multi-agent chemotherapy that is associated with considerable treatment-related toxicity and mortality, especially in older patients. We hypothesized that the regimen DA-EPOCH may be effective in BL, based on the observation that it overcomes the adverse effect of high proliferation in diffuse large B-cell lymphoma. Methods: We investigated DA-EPOCH-rituximab (R) in untreated BL in an attempt to maintain the high cure rates of standard therapy with minimal treatment related toxicity. Eligible patients had a diagnosis of untreated BL and could be HIV negative or positive with HIV negative patients (n=13) receiving 6 cycles of DA-EPOCH-R as previously described (Blood 99: 2685, 2002) and HIV positive (n=6) patients receiving 3–6 cycles of DA- EPOCH-R for 1 cycle beyond CR for a minimum of 3 cycles. All patients received intrathecal methotrexate prophylaxis and outpatient therapy where possible. Results: The characteristics of 19 enrolled patients are: median age (range) 29 (18–66) and ECOG PS 1(1–3); stage III/IV 10 (53%); LDH > N 11 (61%); male sex 15 (79%); extranodal sites 13 (68%) and ileocecal disease 13 (68%). No patients so far had CNS involvement at diagnosis. Response is CR/CRu in 100% of patients with one patient receiving consolidative radiotherapy to a site of residual disease. OS and PFS are both 100% and EFS 93.3% at a median potential follow-up time of 29 months. Toxicities were fever/neutropenia in 16%, grade 4 neutropenia in 47% and grade 3/4 thrombocytopenia in 22% of cycles. There was one case of tumor lysis syndrome and no treatment related deaths. Conclusions: DA-EPOCH-R is highly effective in BL. It appears to be associated with much lower toxicity compared to standard high-dose regimens and may significantly advance the therapeutic index of BL treatment. Accrual continues. No significant financial relationships to disclose.