bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final result of phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for elderly patients with small cell lung cancer (SCLC)
Authors: Ishimoto O. , Inoue A. , Sugawara S. , Harada M. , Usui K. , Suzuki T. , Yokouchi H. , Maemondo M. , Nukiwa T. 
Published: August 2020

8054 Background: AMR, a new anthracycline agent, is active for SCLC. We had previously reported a phase I study of AMR combined with CBDCA for elderly patients with SCLC (J Thorac Oncol 1:551, 2006). The objective of this study is to evaluate the efficacy and the safety of this combination for elderly patients with SCLC. Methods: Chemotherapy naïve elderly patients (70 years or older) with SCLC received AMR (35 mg/m2, day1–3) and CBDCA (AUC 4.0, day1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 60% in eligible pts would indicate potential usefulness while ORR of 40% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, the estimated accrual was 30 patients. Results: From January 2005 to November 2007, 36 pts were enrolled from 11 institutions. Patient characteristics were: Male/Female 27/9; median age 76 (range 70–83); Performance status 0/1 17/19. The median numbers of treatment cycles were 4 (range 2–7). The objective responses were CR 1, PR 31, SD 2, PD 2, and the ORR was 89%. Median PFS was 5.8 months and median survival time was 18.6 months. Grade 3–4 neutropenia was observed in all the patients and 5 patients (14%) suffered from grade 3–4 febrile neutropenia. Other toxicities were moderate and no treatment related death was observed. Conclusions: AMR combined with CBDCA is quite effective for SCLC with acceptable toxicities even for the elderly population. Further evaluation of this regimen is warranted. No significant financial relationships to disclose.
A randomized phase II study of a combination of docetaxel and S-1 versus docetaxel monotherapy in pts with NSCLC previously treated with platinum-based chemotherapy: Results of Okayama Lung Cancer Study Group (OLCSG) trial 0503
Authors: Segawa Y. , Hotta K. , Takigawa N. , Matsuo K. , Yoshioka H. , Hayashi H. , Nogami N. , Tabata M. , Kiura K. , Tanimoto M. 
Published: August 2020

8058 Background: Recent studies have demonstrated that docetaxel (DOC) monotherapy provides a significant survival prolongation in relapsed pts with NSCLC. However, its benefit remains modest and further improvement is needed. S-1 is a newly developed oral 5-fluorouracil derivative, possessing a promising anti-tumor activity in NSCLC. Based on a superior effect of combination of DOC and 5-fluorouracil derivative (capecitabine) to DOC alone in anthracycline-pretreated breast cancer pts, we conducted a randomized phase II study to evaluate the clinical significance of adding S-1 to DOC in the second-line setting. Methods: Pts with relapsed NSCLC to the first-line platinum-based chemotherapy were randomly allocated to DOC monotherapy (A arm; 60 mg/m2, day 1, q 3 wks) or a combination chemotherapy (B arm) of DOC (40 mg/m2, day 1, q 3 wks) and S-1 (80 mg/m2, days 1 to 15). The doses of arm B were determined based on the results of a phase I study conducted for Japanese pts with gastric cancer (Anticancer Res 24: 1843, 2004). The primary endpoint was response rate and secondary endpoints included OS, PFS and toxicity. Results: Between 2005 and 2008, 60 pts were enrolled (A/B: 29/31 pts). Demographics of the pts were as follows: M/F: 49/11, Ad/others: 40/20, ECOG-PS 0/1: 38/22. A median number of courses administered was 4 (range: 1 to 6). Objective response was obtained in 6 (20.7%) and 5 pts (16.1%) in arms A and B, respectively. With a median follow-up time of 16.9 months, MST and median PFST in arm A were longer than arm B (22.9 vs. 8.7 months and 3.7 vs. 3.4 months, respectively). The major toxicity was myelosuppression, with grade 4 neutropenia of 62% vs. 29%, whereas thrombocytopenia was generally mild. Grade 3 febrile neutropenia was observed in 4 and 1 pts, none of whom further developed grade 5 toxicity. Other grade 3 or greater non-hematological adverse events included fever (B: 1 pt), pneumonitis (B: 1 pt), liver dysfunction (B: 2 pts), skin rash (B: 1 pt), and all of them were improved with an appropriate supportive care. Conclusions: The trial suggests that docetaxel monotherapy remains a standard therapy for NSCLC pts who relapsed to platinum-based chemotherapy. No significant financial relationships to disclose.
Characteristics and outcomes of non-small cell lung cancer (NSCLC) patients (pts) carrying epidermal growth factor receptor (EGFR) mutations who progress after initial erlotinib (E) response
Authors: Cardona Zorrilla A. F. , Moran T. , Reguart N. , Porta R. , Queralt C. , Cardenal F. , Carrasco-Chaumel E. , Massuti B. , Taron M. , Rosell R. 
Published: August 2020

8064 Background: Most NSCLC pts with EGFR mutations respond to E; however, resistance to this tyrosine kinase inhibitor (TKI) can be acquired. The resistant T790M mutation has been identified in 50% of progressing pts. We assessed pt characteristics and outcome to additional treatment in 55 EGFR mutated pts after progression to E. Results: Pts mean age was 59±12.5 years; 65% females; 94% never-smokers; 54 adenocarcinoma. 35 pts (63%) were PS ≤2; main metastasis sites were lung (39/71%), bone (21/38%) and liver (10/18%). 22 and 25 pts received E as first- or second-line treatment, respectively. Mutations in tumor were: 65% DelE19 (Δ746–750), 35% L858R mutation; with 31% and 20% serum detection respectively. For the complete cohort, overall response rate (ORR) with E was 78% and time to progression (TTP) was 11.2 months (m) (range, 4–29 m). After progressing to E, 8 pts were re-biopsied, of whom 2 had the T790M mutation; 9 had the T790M mutation in serum (16%). 49% received platinum-based chemotherapy, 14.5% E plus another agent (bevacizumab, fulvestrant, vorinostat), 25.5% single-agent chemotherapy and 11% a non-reversible TKI (HKI-272). ORR for first-line post-E treatments was 33% (CR 1/PR 9) and median TTP was 8 m (range, 4.1–11.8 m). There were no differences in TTP according to gender (p = 0.10), type of mutation (p = 0.63) or severity of skin toxicity (p = 0.16). 11 pts received a second-line post-E treatment with E plus chemotherapy, achieving an ORR of 40%. Median survival was 27 m for all 55 pts (range, 22.9–31.1 m). Conclusions: Pts with EGFR mutations present a biologically different disease which continued to be sensitive to other treatments after progressing to E. No significant financial relationships to disclose.
A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status
Authors: Sequist L. V. , Gettinger S. , Natale R. , Martins R. , Lilenbaum R. , Jänne P. , Gray J. , Samuel T. A. , Grayzel D. , Lynch T. J. 
Published: August 2020

8073 Background: IPI-504 (retaspimycin hydrochloride) is a potent, water-soluble heat shock protein 90 (Hsp90) inhibitor. IPI-504 causes the degradation of mutated epidermal growth factor receptor (mtEGFR) kinase and cMET in NSCLC cell lines. IPI-504 also significantly reduces tumor growth in murine xenograft models, including tumors resistant to tyrosine kinase inhibitors (TKIs). Methods: This phase II trial is investigating the safety and antitumor activity of intravenous (IV) 400 mg/m2 IPI-504 given twice weekly for 2 out of 3 weeks. Eligible patients (pts) had stage IIIb (w/ malignant effusion) or stage IV NSCLC that progressed after TKI treatment. EGFR mutation analysis was performed on all pts. Two cohorts (n=10 each) were initially enrolled and stratified by EGFR status (mtEGFR or wtEGFR). Planned cohort expansion to 29 pts occurred if ≥ 1 pt from that cohort had a best response of stable disease (SD) ≥12 wks or partial response (PR). Pts were evaluated for safety and RECIST response every 6 weeks. Central, independent radiology review was performed for all imaging studies. Results: 43 pts have been enrolled: 10 mtEGFR, 17 wtEGFR, 12 pending analysis, and 4 EGFR-failed samples. 19 pts are currently on study. Median age is 62 yrs (range 31–77). Median no. of prior therapies is 3. Common related adverse events are fatigue, nausea, and diarrhea. Anti-tumor activity has been observed, see table. Both cohorts have been expanded. Conclusions: IPI-504 monotherapy has been well tolerated, with evidence of anti-tumor activity, particularly and unexpectedly in the wtEGFR cohort. These data suggest that IPI-504 may have antitumor activity in heavily pretreated pts with advanced NSCLC. Further evaluation continues in the expansion phase of the trial. [Table: see text] [Table: see text]
Prognostic factors in advanced NSCLC: Experience from the FLEX trial
Authors: Pirker R. , Rodrigues-Pereira J. , Szczesna A. , Von Pawel J. , Krzakowski M. , Ramlau R. , Vynnychenko I. , Park K. , Emig M. , Gatzemeier U. 
Published: August 2020

8083 Background: The FLEX trial demonstrated superior survival for cisplatin/vinorelbine plus cetuximab versus cisplatin/vinorelbine alone in patients with advanced EGFR-positive NSCLC. Here we report on the prognostic factors observed in the trial independent of cetuximab treatmentMethods: 1125 patients were randomized to cisplatin/vinorelbine plus cetuximab or cisplatin/vinorelbine alone. Prognostic factors were determined by both univariate and multivariate analyses. Results: Patient baseline characteristics were: 70% male, median age 59 (18–83) years, 31% older than 65 years, 94% stage IV, 47% adenocarcinoma, 34% squamous cell carcinoma, 83% ECOG 0/1. The trial confirmed the following prognostic factors in the univariate analysis: gender, performance status, histology, smoking status, and ethnicity. Females had longer survival than males (12.7 versus 9.3 months). Patients with ECOG performance status 0, 1, and 2 had median survival times of 13.5, 10.6 and 5.9 months, respectively. Patients with adenocarcinomas had a median survival of 12.4 months and those with squamous cell carcinomas had a median survival of 9.3 months. Smokers, former smokers, and never-smokers had median survival times of 9.0, 11.1 and 14.6 months, respectively. Outcome was better for Asians (n=121) compared to Caucasians (n=946) (median 19.5 versus 9.6 months). Age <65 and age ≥65 did not indicate prognosis. Multivariate analysis confirmed the prognostic significance of performance status, gender, smoking status, region (Europe versus Australasia), and histology. Conclusions: The FLEX trial confirmed several prognostic factors, including gender, performance status, histological subtype, ethnicity, and smoking status for patients with advanced NSCLC. [Table: see text]
Lung cancer in women: The Spanish female-specific database WORLD 07
Authors: Vinolas N. , Magem M. , Garrido P. , Artal A. , De Castro J. , Campelo R. G. , Isla D. , Felip E. , Amador M. , Rosell R. 
Published: August 2020

8084 Background: Lung cancer is the leading cause of cancer mortality among women in many countries. Gender differences have been reported, most of them based on retrospective analysis. Methods: WORLD07 is a prospective, multicenter, epidemiologic female-specific lung cancer database developed by the Spanish Lung Cancer Group. Data on demographics, previous cancer history, reproductive and hormonal status, diet, alcohol, tobacco, and occupational information are being collected just as histology, stage, treatment and survival. Results: From October 2007 to Nov 2008, 342 female newly diagnosed of lung cancer were collected in an e-database in 20 Spanish centers. Patients (p) characteristics are: median age 61.7 years (y) (range: 36 - 87); Caucasian: 98.2%; Marital status (%): married 67.7, unmarried 11.2, divorced 7.1, widow 14. Educational level (%): basic 57.4, secondary 29.1, university 13.5. Median age of menarche 12.7 y. Children: 79.4% (median: 2); Median age of first child 27 y. Oral contraceptive: 30.6%. Pre-menopausal 15.4%,postmenopausal 84.6%. Median age of menopause 46.7 y. HRT: 5.3%. Median duration of HRT: 4.4 y. Obesity: 11.3%. Smoking habit (%): never (passive smoker/no exposition)/former/current smokers: 42 (42.8/57.2) /19 /39; Median packs/year 72.4. Former smokers: 1–5/5–10/10–15/>15 y (%): 51/11.8/7.8/29.4. Work exposure 3.5%. Alcohol consumption 3.2%. Familial history of cancer: 45.5% (lung cancer 29.7%). Previous history of cancer 13.8% (breast 33.3%). Current lung cancer histology (%): adenocarcinoma/BAC/squamous/large cell/NOS: 70.4/5.7/10.4/7.9/5.7. SCLC 11.8%. TNM I/II/III/IV (%): 16/3.9/28.7/51.4. Surgical treatment 24.7 % (lobectomy/pneumonectomy/exploratory: 85.5/9.2/5.3%). Available data of 122 stage IV NSCLC p: 74.6% receive chemotherapy, 92.3% of them two drugs and 68.9 % platinum-based (59% cisplatin). EGFR mutations analysis 7.9%. Conclusions: According this series, 42% of Spanish lung cancer women are never smokers and 70.4% have adenocarcinoma. Other collected information, choice of treatment and survival outcomes will be also analyzed. No significant financial relationships to disclose.
Using health-related quality of life (QL) parameters as primary endpoints in a multinational prospective NSCLC chemotherapy (chemo) trial: The Asia-Pacific QL trial
Authors: Gralla R. J. , Hollen P. J. , Thongprassert S. , Kim H. , Yuankai S. , Hsia T. , Wu C. , Park K. , Liu T. 
Published: August 2020

8086 Background: Survival and QL improvements are major goals in treating advanced NSCLC. Enhancing survival for all treated patients (pts) with advanced NSCLC beyond that achieved with 3rd generation chemo regimens is difficult in this highly symptomatic cancer; questions remain as to the impact of chemo on QL and symptoms (“PROs” or patient reported outcomes). This study was designed to: 1) evaluate the impact of chemo on QL and symptoms for all pts, 2) evaluate QL by response category (CR+PR = MR or major response, stable disease = SD, and progression); and 3) test whether barriers in QL evaluation are overcome by using a computer-assisted validated instrument (LCSS-QL). Methods: All pts received initial docetaxel-based chemo (83% with cisplatin or carboplatin) based on known response and survival results (Fossella JCO 2003) and were assessed every 3 weeks with the LCSS-QL. Results: 300 pts are entered and 243 evaluated; 91% have repeated QL measures through 3 cycles of chemo in this ongoing trial. Demographics: 77% Stage IV; 72% men; 67% adenocarcinoma; median age 58; KPS 90–100 = 66%, 70–80 = 34%. A 37% MR rate was achieved. QL feasibility: high patient and staff acceptability found (at 43 sites, 8 countries). For the whole group (using 5% as a minimally important difference), after 3 chemo cycles all 9 LCSS parameters were stable, except overall QL and cough (> 5% and 7% improvements). Evaluating PROs by chemo response: in all parameters after completion of only 2 chemo cycles, pts with MR had better symptom control than pts with progression (p<0.05 in 4 of the 6 major symptoms after cycle 3). Total LCSS-QL score was better for pts with MR (p=.007) or SD (p=.03) compared with progressive NSCLC. Conclusions: For docetaxel-based chemo: 1) MR is associated with better symptom control and total QL than SD or progression; 2) even with only a minority (37%) having a major response, QL and PRO parameters are stable or better for the whole group by key decision points of 2 and 3 chemo cycles; 3) with 91% compliance with the computer-assisted LCSS-QL, evaluation of QL in multiple centers is achievable during chemo trials. This study demonstrates that QL and PRO evaluation is feasible and should influence chemotherapy treatment decisions. [Table: see text]
Prognostic and predictive impact of EGFR and K-ras mutation, and EGFR gene copy number in patients with advanced non-small cell lung cancer (NSCLC) who received first-line cytotoxic chemotherapy
Authors: Tambo Y. , Kasahara K. , Sone T. , Kimura H. , Sakai A. , Araya T. , Ueda A. , Fujimura M. , Nakao S. 
Published: August 2020

8096 Background: Epidermal growth factor receptor (EGFR) mutations, amplification, and K-ras mutations are known as predictive factor of the EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients (pts) with NSCLC. Prognostic influences of those biomarkers remain the matter to be discussed. Methods: Consecutive pts with advanced NSCLC who were examined EGFR genotype and received 1st line cytotoxic chemotherapy were enrolled. EGFR amplification and K-ras mutation were analyzed if sufficient tumor samples were available. Results: 87 pts were enrolled in this study. EGFR mutations or K-ras mutations were found in 26 of 87 (29.9%) or 2 of 65 (3.1%) pts, respectively. As to objective response rate (ORR), no significant differences were observed among pts with EGFR mutations, K-ras mutations, and pts without both mutations. Progression free survival (PFS) in 1st line cytotoxic chemotherapy was 8.4, 1.0, and 3.9 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. PFS was longer in pts with EGFR mutations compared with the pts without both mutations (p=0.0234). We also found the pts with K-ras mutations had shorter PFS compared with pts without both mutations (p=0.0203). Overall survival (OS) was 29.7, 2.3 and 13.4 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. Significant differences were found between pts with EGFR mutation and without both mutations (p=0.0001) and between pts without both mutations and with K-ras mutations (p=0.0001). Pts with EGFR amplification were found in 21 of 78 (26.9%). There were no differences between EGFR amplification positive and negative in terms of ORR, PFS and OS. 87 of 68 (78.2%) pts received EGFR-TKI therapy in the second line or later. As previously reported, both EGFR mutations and amplifications were good predictive marker of ORR, PFS and OS in pts treated with EGFR-TKI. Conclusions: EGFR mutations were good predictive marker and K-ras mutations were poor predictive marker in first line cytotoxic chemotherapy. There is the possibility that EGFR and K-ras mutations have the prognostic impact in advanced NSCLC. [Table: see text]
RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced NSCLC patients treated with cisplatin-based chemotherapy
Authors: Zhou C. , Zhou S. , Zhang L. 
Published: August 2020

8097 Background: Platinum-based chemotherapy is the standard treatment for advanced NSCLC patients. RRM1 and BRCA1 are important regulators of chemosensitivity of NSCLC. Methods: Stage IIIb/IV NSCLC patients were given cisplatin-based chemotherapy based upon expression levels of RRM1 and BRCA1 mRNA in the tumor. Expression levels of the two genes were determined by real-time PCR and cut-off points were reported in our previous study. The patients with low expression of RRM1 were treated with gemcitabine/cisplatin up to 4 cycles. The others were treated with vinorelbine or paclitaxel plus cisplatin up to 4 cycles. After the chemotherapy, the patients were followed every 6 weeks up to disease progression and then every 3 months up to death. Results: 90 chemonaive, stage IIIB/IV, PS 0–1 NSCLC patients were enrolled. Age 60 (40–78) yrs old, male/female: 73/27%; adenocarcinoma/squamous/adeno-squamous/undefined NSCLC: 49/33/11/7%;,stage IIIb/IV: 13/87%. Overall response rate was 41.1%, stable disease 42.2%, progressive disease 16.7%. Disease was not progressive in 33 patients. Median TTP was 5 months. Response rate and TTP were better in those with low RRM1 expression ( Table ). Toxicity of the chemotherapy was acceptable. Overall survival will be reported in the conference. Conclusions: RRM1 and BRCA1 mRNA expression levels in non-small cell lung cancer are associated with clinical outcome to cisplatin-based chemotherapy. Prospective studies are ongoing to evaluate the role of the two genes in tailoring chemotherapy in our center. [Table: see text] No significant financial relationships to disclose.
Ligands of EGFR and the insulin-like growth factor family as serum biomarkers for response to EGFR-inhibitors in patients with advanced NSCLC
Authors: Vollebergh M. A. , Kappers I. , van den Heuvel M. M. , Buning-Kager J. C. , Korse C. M. , Bonfrer J. M. , Hauptmann M. , de Visser K. E. , Klomp H. M. , Linn S. C. 
Published: August 2020

8100 Background: To determine whether concentrations of transforming growth factor α (TGFa), amphiregulin (ARG), both ligands of the epidermal growth factor receptor (EGFR), insulin-like growth factor 1(IGF1) or IGF-binding protein 3 (IGFBP3) measured in serum of advanced non-small cell lung cancer (NSCLC) patients are predictive of EGFR-inhibitors (EGFRi) response. Methods: We assessed serum levels of marker candidates using ELISA (TGA and ARG) and chemiluminescent (IGF1 and IGFBP3) assays. Sixty-one advanced NSCLC patients treated with EGFRi (gefitinib or erlotinib, >14 days) were matched for gender, age and histology to a control group of 63 EGFRi-untreated advanced NSCLC patients. We dichotomized marker levels at the 20th, 50th or 80th percentile and evaluated whether the effect of EGFRi treatment on overall survival (OS) differed by marker level based on multivariate proportional hazards regression with an interaction term. We adjusted for gender, smoking, stage, histology and prior chemotherapy. Results: While 6-months OS did not appreciably differ between 50 EGFRi treated and 50 control patients whose TGFa levels were below the 80th percentile (39% vs. 54%, multivariate HR 0.78, 95% CI 0.45–1.34, p=0.359), it was substantially worse for 11 EGFRi treated patients compared with 13 control patients whose TGFa levels were high (9% vs. 42%, multivariate HR 2.38, 95% CI 0.87–6.52, p=0.092). The difference of EGFRi effects by TGFa level was statistically significant (interaction p=0.033). There was no evidence that EGFRi treatment effects differed by levels of ARG, IGF1 and IGFBP3. Patients with high concentrations of IGFBP3 (above the median) had significantly longer OS than patients with low IGFBP3 concentrations, independent of treatment (HR 0.46, 95% CI 0.29–0.73, p=0.001). Conclusions: This is the first study in NSCLC patients of Caucasian origin in which serum concentrations of TGFa are predictive for EGFR-inhibitor response, suggesting this is a potential predictive marker for EGFRi treatment. Furthermore, we coincidentally found that levels of IGFBP3 are predictive for overall survival, indicating this might be a prognostic factor in advanced NSCLC patients. [Table: see text]