bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase Ib/II study of DMXAA combined with carboplatin and paclitaxel in non-small cell lung cancer (NSCLC)
Authors: McKeage M. 
Published: March 2020

7102 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics including taxanes and platinum agents. This phase Ib/II study evaluated DMXAA in combination with carboplatin (C) and paclitaxel (P) in NSCLC. Methods: Patients had histologically confirmed stage IIIb or IV NSCLC previously untreated with chemotherapy. Safety of the combination was initially assessed in 1 patient receiving C (AUC 6 mg/ml × min) + P (175 mg/m2) + 600 mg/m2 DMXAA. Seventy-seven patients were then randomised to receive up to 6 cycles of C + P with or without DMXAA (1,200 mg/m2 or 1,800 mg/m2). Safety assessments included EKG, adverse events, laboratory screens, pharmacokinetics and ophthalmic exams. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 78 patients were enrolled. One received C + P + 600 mg/m2 DMXAA; no serious toxicities were observed; the patient had a partial response (PR, RECIST, investigator assessment). Randomisation was initiated: 35 patients received C + P, 36 C + P + 1200 mg/m2 DMXAA and 6 C + P + 1800 mg/m2 DMXAA. The safety profile in the control and DMXAA arms was comparable. No pharmacokinetic interactions were observed. Investigator-assessed RECIST data are available from 68 patients with at least one post-baseline CT scan. First post-baseline scans were taken after the defined stable disease interval (6 weeks), so patients without progressive disease (PD) at this point have confirmed disease control (best overall RECIST response of PR or stable disease (SD), with final disposition dependent on subsequent scans). Of 30 patients in the control arm 23 show disease control and 7 PD. Of 33 patients in the 1200 mg/m2 DMXAA arm 28 show disease control and 5 PD. Of 5 patients who received 1800 mg/m2 DMXAA, all show disease control, with 3 confirmed PRs. Conclusions: Addition of DMXAA to standard doses of C and P did not add significantly to toxicity. Initial response data suggest this combination could provide additional benefit compared with C and P alone. No significant financial relationships to disclose.
A phase II study of a novel anti-tubulin, E7389, in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Das A. , Spira A. , Iannotti N. , Savin M. , Zang E. , Datta K. , Shapiro G. , Patturajan M. , Silberman S. 
Published: March 2020

7106 Background: E7389, a synthetic analog of halichondrin B that was isolated from a marine sponge, has broad anti-proliferative activity at nanomolar levels and a unique profile of tubulin interactions. Methods: This is an open-label, single-arm, stratified phase II study of E7389 in patients with measurable, recurrent and/or metastatic NSCLC who progressed during or after platinum-based doublet chemotherapy. E7389 (1.4 mg/m2) was administered as a bolus IV on days 1, 8, and 15 of a 28-day cycle to 72 patients (cohort 1) in stratum I (55 taxane pretreated patients) and stratum II (17 taxane-naive patients) and on Days 1 and 8 of a 21-day cycle (cohort 2), providing an additional 22 patients in stratum I. The primary efficacy endpoint was objective response rate to E7389 monotherapy. Results: As of 9 December 2005, 94 evaluable patients received E7389. Nineteen tumors were classified as squamous cell carcinomas, 39 as adenocarcinomas, and 36 were large cell carcinomas or unclassified. The median number of cycles completed was 3. Fifteen patients completed 6 or more cycles and 75 patients underwent tumor assessments after cycle 2. Major toxicities related to study drug included myelosuppression, nausea, fatigue, dehydration, arthralgias, dyspnea, and peripheral neuropathy. Based on RECIST criteria, 6 partial responses (PR) were observed among 94 evaluable patients (PR rate = 6.4%, 95% CI: 2.8%, 12.8%). For 33 patients the best response was stable disease (SD rate = 35.1%, 95% CI: 25.5%, 45.1%). Disease control rate (PR + SD) was 41.5% (95% CI: 31.4%, 51.7%). For cohort 1, the 12-week progression free survival rate was 57.2%. As of 9 December 2005, median PFS time was 108 days (95% CI = 55, min-max = 1–239+). Cohort 2 is being followed to estimate their 12-week PFS. The correlation of beta tubulin isotype, stathmin, microtubule-associated protein 4 (MAP4) and tau protein mRNA expression with tumor responses is on-going. Conclusions: Based on this data, E7389 has been shown to be safe and effective in the treatment of NSCLC patients. Updated information and results of molecular correlations of responses will be presented. [Table: see text]
EGFR, HER2, and phospho-Akt are not predictive factors for response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Toschi L. , Metro G. , Magrini E. , Bartolini S. , Ligorio C. , Finocchiaro G. , Pession A. , Cancellieri A. , Tallini G. , Cappuzzo F. 
Published: March 2020

7111 Background: Response to Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is significantly associated with increased EGFR gene copy number, increased EGFR expression or presence of activating EGFR gene mutations. In presence of EGFR, increased HER2 gene copy number, as well as activation of the anti-apoptotic protein Akt demonstrated to increase EGFR-TKI sensitivity in both clinical and preclinical models. Aim of the present study was to assess whether these biomarkers also associate with response to first-line chemotherapy. Methods: Patients with advanced NSCLC with full clinical data and with tumor tissue available were selected for this analysis. Specimens were evaluated for EGFR and HER2 gene copy number by FISH, EGFR and p-AKT protein expression by immunohistochemistry. RECIST criteria were used to assess response to chemotherapy. Results: A total of 144 NSCLC were included in this analysis. Patient characteristics included: male/female: 95/49; PS 0/1/2: 112/29/3; stage III/IV: 44/100; adenocarcinomas plus bronchioloalveolar/squamous/other: 86/35/23; never/former/current smokers: 26/69/49. The majority of patients were treated with first-line platinum-based chemotherapy (115/79.9%). Response to chemotherapy was not associated with any clinical characteristic. A trend towards better response was observed in non-adenocarcinoma histologies (p = 0.08) and in smokers (p = 0.20). Response and time to disease progression (TTP) were not influenced by EGFR/HER2 FISH status, nor P-Akt/EGFR expression. In EGFR FISH positive response rate was 36.4% and TTP was 6.4 months, versus 28.7% and 7.3 months in EGFR FISH negative (p = 0.4 for both). Conclusions: Biomarkers useful for selection of patients candidate for TKI therapy are not predictive for response to first-line chemotherapy in NSCLC. No significant financial relationships to disclose.
Trends in demographics and survival for patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Kubota K. , Masuhara H. , Hosoya K. , Yoh K. , Niho S. , Goto K. , Ohmatsu H. , Nishiwaki Y. , Saijo N. 
Published: March 2020

7114 Background: In clinical trials, concurrent chemoradiotherapy improves survival of pts with inoperable stage III NSCLC compared with sequential chemoradiotherapy or radiotherapy alone, and platinum doublets with third-generation chemotherapy prolong survival of pts with stage IV NSCLC. Epidermal growth factor receptor antagonist is active as second-line chemotherapy. Few outcomes research regarding demographics and survival trends in advanced NSCLC has been conducted. Methods: The National Cancer Center Hospital East Database was searched for all pts with inoperable stage III and IV NSCLC. Data was recorded for histology, age, sex, smoking history, tumor location, stage, performance status (PS), and treatment modality. Pts were divided into two groups; group A: newly registered pts from July 1992 to December 1997, group B: from January 1998 to June 2004. Survival curves were evaluated using the Kaplan-Meier methods, and statistical significance was estimated by the log-rank test. Results: 2,135 pts (771 pts group A vs. 1364 pts group B) were identified. Pts demographics of each group (% group A/B) were as follows; male; 74/77, non-smoker; 19/19, PS 0–1; 79/85, squamous cell histology; 26/24, stage III; 45/44. Median age was 63 years old in group A and 64 in group B. Median survival (MS), 1-year survival rate (1ys), 2ys and 3ys were 8 months (M), 33%, 12% and 7% in group A, 10M, 42%, 23% and 14% in group B, respectively (P < .0001). In pts with stage III, MS, 1ys, 2ys, 3ys were 12M, 46%, 20%, 12% in group A and 15M, 56%, 34%, 20% in group B (P < .0001). In non-smoker, MS, 1 ys, 2 ys were 11 M, 46%, 19% in group A and 15 M, 56%, 30% in group B (P < .0001). In females, MS, 1 ys, 2 ys were 10 M, 39%, 16% in group A and 15 M, 55%, 31% in group B (P < .0001). Conclusion: Although there were no apparent differences in demographics between the two groups, survival was significantly improved chronologically. The improvement was prominent in stage III, non-smokers and females suggesting the benefit of chemoradiotherapy and tyrosine kinase inhibitors. [Table: see text]
The Four-Arm Cooperative Study (FACS) for advanced non-small cell lung cancer (NSCLC): A subgroup analysis in elderly patients (pts)
Authors: Goto K. , Nishiwaki Y. , Saijo N. , Takeda K. , Katakami N. , Kudoh S. , Ichinose Y. , Ohashi Y. , Ariyoshi Y. , Fukuoka M. 
Published: March 2020

7115 Background: Efficacy and safety in fit, elderly NSCLC pts receiving platinum-based treatment have been reported to be similar to those in younger pts. However, there is controversy about which platinum-based regimens are suitable for the elderly. To compare efficacy and safety of platinum-based chemotherapy regimens in the elderly, we conducted an age specific subgroup analysis on FACS, a phase III randomized trial comparing four platinum-based regimens for advanced NSCLC. Methods: FACS was designed to compare three platinum-based combination regimens to cisplatin (80 mg/m2, day 1) plus irinotecan (60 mg/m2, days 1, 8, 15) (IP) as the reference arm. The experimental regimens were: carboplatin (AUC 6, day 1) plus paclitaxel (200 mg/m2, day 1) (TC); cisplatin (80 mg/m2, day 1) plus gemcitabine (1000 mg/m2, days 1, 8) (GP); cisplatin (80 mg/m2, day 1) plus vinorelbine (25 mg/m2, days 1,8) (NP). Results: Of the 105 pts ≥ 70 years (17% of 602 enrolled pts), 27 were on the IP arm, 27 on TC, 28 on GP, and 22 on NP. Patient characteristics were similar in each arm. Response rates were 26% in IP, 20% in TC, 32% in GP, 50% in NP. Frequency of grade 3 or greater leukocytopenia (IP/TC/GP/NP: 52%/33%/36%/86%) was higher in NP, and thrombocytopenia (IP/TC/GP/NP: 11%/19%/43%/0%) was higher in GP, however anemia (IP/TC/GP/NP: 56%/19%/29%/55%) was lower in TC and GP. Frequency of grade 2 or greater vomiting (IP/TC/GP/NP: 52%/22%/39%/41%) was lower in TC, and diarrhea (IP/TC/GP/NP: 48%/7%/4%/14%) was lower in TC, GP and NP, however, grade 2 or greater sensory neuropathy (IP/TC/GP/NP: 0%/22%/0%/0%) was higher in TC. One year survival rates were 48% for the IP arm, 48% for TC, 61% for GP, and 46% for NP. There were no significant survival differences between IP and each experimental regimen. In addition, no significant differences between ≥ 70 and < 70 years were observed in each treatment regimen regarding hematological and non-hematological toxicities, response rates, and survival, except that grade 3 or greater anemia was significantly higher in ≥ 70 years pts in IP and NP arms. Conclusions: These platinum-based four regimens were similarly active and tolerable for fit, elderly NSCLC pts, and their efficacy and toxicity in the elderly were similar to those in younger pts. No significant financial relationships to disclose.
Radiotherapy vs. temozolomide in the treatment of patients with lung cancer and brain metastases: A nordic randomized phase II study
Authors: Wagenius G. , Brodin O. , Nyman J. , Greim G. , Hillerdal G. , Riska H. , Sundström S. , Grönberg B. , Wang M. , Garmo H. 
Published: March 2020

7136 Background: Metastasis to the brain is the most common intracranial tumour and 20–40% of all cancer patients will develop brain metastases. Lung cancer is the most common primary tumour and compose of 40%-50% of all brain metasases. As the survival in many malignancies increases, brain metastases will be an increasing problem. It is therefore important to find new treatment options. The aim of this study was primary to study quality of life and to compare radiotherapy and Themozolomide in that context. Methods: Inclusion criterias were confirmed small cell or non-small cell lung cancer, multiple brain metastases, PS 0–2, no previous radiotherapy to the brain. Previous chemotherapy was allowed. Patients were randomized to arm A (radiotherapy 30 Gy over 10 fractions) or arm B (Temozolomide 200 mg/m2 day 1–5, new cycle on day 29). Quality of life (QoL) was measured with a general cancer module, EORTC QLQ-C30, and a brain cancer specific module, BCM20. The primary end-point was the proportion of patients in each treatment arm with maintained or better QoL score at 8 weeks compared to the base line evaluation. In this first analysis exclusion rate from the study at 8 weeks was used as a surrogate end-point. Results: 208 patients were included, 104 in arm A and 104 in arm B. 36 (17%) squamous cell, 97 (47%) adenocarcinomas, 10 (5%) large cell, 23 (11%) undifferentiated and 42 (20%) small-cell lung cancer were included. 93 (45%) patients were chemonaive. At 8 weeks, 79 patients were excluded from the study, 51 (49%) from the temozolomide arm and 28 (27%) from the radiotherapy arm. 53% of the patients with squamous cell carcinoma were excluded compared to 40% of small cell lung cancer, 33% of adenocarcinomas and 27% of large cell carcinomas. The exclusion rate at 8 weeks was higher among patients with symptoms at randomization compared to patients without symptoms. There were no difference in exclusion rate when comparing number or size of the metastases. Conclusion: The exclusion rate at 8 weeks was higher in the temozolomide arm compared to the radiotherapy arm. Histopathology and symptoms at randomization seems to be factors influencing the exclusion rate whereas number or size of metastases does not. Survival and quality of life data will be presented at the meeting. No significant financial relationships to disclose.
Phase II pharmacodynamic trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy: FISH results
Authors: Felip E. , Rojo F. , Reck M. , Heller A. , Klughammer B. , Maacke H. , Möcks J. , Brennscheidt U. , Gatzemeier U. , Baselga J. 
Published: March 2020

7160 Background: The HER1/EGFR inhibitor erlotinib significantly prolongs survival of patients with previously-treated advanced NSCLC. Methods for selecting patients most likely to derive clinical benefit from erlotinib are not established. Increased HER1/EGFR gene copy number has been suggested as a potential predictive biomarker of clinical benefit, and was investigated in this phase II study. Methods: Advanced NSCLC patients who failed first line chemotherapy were treated with erlotinib monotherapy, 150 mg/d p.o. Each patient underwent tumor biopsy before start of treatment. Tumor HER1/EGFR gene amplification status was assessed using FISH, and classified as positive (amplification, polysomy, high polysomy) or negative (disomy, trisomy). Results: 83 patients were included: median age 56 (range 35–78); sex: male 72%, female 28%; histology: adenocarcinoma 43%, large cell 31%, squamous cell 19%, others 7%; smoking status: 44 current smokers, 28 former smokers, 11 never smokers. Of 73 evaluable patients, 7 (10%) achieved partial response (PR), 28 (38%) had stable disease (SD) and 38 (52%) had disease progression. PRs were observed in 4 males / 3 females; in 5 adenocarcinomas / 1 large cell/ 1 squamous cell; in 2 current / 3 former / 2 never smokers. Erlotinib was well tolerated and no unexpected toxicities were seen. HER1/EGFR gene copy number was evaluated in 53 patients. 15 patients were FISH +, 10 of whom achieved clinical benefit (PR, or SD for ≥12 weeks). Only 5 of 38 FISH - patients had clinical benefit. FISH + patients achieved a longer median time to progression (137 vs 43 days; p = 0.00011; HR 0.35) as well as overall survival (226 vs 115 days; p = 0.3221, HR 0.722). Conclusion: In this study, increased HER1/EGFR gene copy number was associated with a better outcome on erlotinib therapy. [Table: see text] [Table: see text]
Phase II trial of erlotinib in elderly patients (age > 70) with previously untreated advanced non-small cell lung cancer (NSCLC): An analysis of quality of life and symptom response
Authors: Jackman D. M. , Yeap B. , Lucca J. , Ostler P. A. , Morse L. K. , Fidias P. , Lynch T. J. , Temel J. , Johnson B. E. , Janne P. A. 
Published: March 2020

7168 Background: Elderly patients derive survival benefit but significant toxicity from chemotherapy for NSCLC. Erlotinib is associated with reasonable toxicity and has a survival benefit for relapsed patients previously treated with 1–2 chemotherapy regimens. This targeted agent may prove an effective and well-tolerated first-line therapy in elderly patients with advanced disease. Methods: 80 patients (chemo-naïve, age ≥ 70, PS 0–2, stage IIIB/IV NSCLC) were treated with erlotinib 150 mg/d as part of a phase II study. Primary endpoint was survival. QoL was a secondary endpoint, as assessed by LCSS at baseline and q4 weeks until progression. The primary endpoint of QoL analysis was to determine changes from baseline in LCSS score. Patients were eligible for QoL analysis if they completed an LCSS questionnaire at baseline and ≥ 1 other monthly follow-up visit. Each of 9 items was assessed on a 100mm visual analog scale from 0 (best) to 100 (worst); symptom improvement or worsening was based on a change of ≥ 10mm, with decreased scores implying improvement. Score differences between the baseline and best follow-up response of each subscale and total LCSS are assessed by the signed rank test. Results: 64 patients (80%) were eligible for QoL analysis. There was a trend towards improvement in QoL, based on the total LCSS score. Statistically significant improvements in dyspnea, cough, fatigue, and pain were seen, both in terms of median changes from baseline and the proportion of patients improved (Table). No patients were symptomatic for hemoptysis at baseline, so improvement could not be calculated. Conclusions: Erlotinib in elderly patients with advanced NSCLC was associated with encouraging survival (10.9 mo), a trend towards improved QoL, and statistically significant improvements in key symptoms of dyspnea, cough, fatigue, and pain. Mixed effects longitudinal modeling showing changes in LCSS over time will be presented at the conference. [Table: see text] [Table: see text]
IFCT0401-bio trial: Pathological and EGF-r molecular analysis of tumor-biopsy samples from patients with non-resectable, pneumonic-type adenocarcinoma (P-ADC) treated by gefinitib. Preliminary results from surgical specimens
Authors: Cadranel J. , Wislez M. , Coulet F. , Poulot V. , Morã J. F. , Debove P. , Perol M. , Souquet P. J. , Soubrier F. , Antoine M. 
Published: March 2020

7185 Background: P-ADC is often a bronchioloalveolar carcinoma (BAC) variant in the 2004 WHO pathological classification. A French prospective multicentric phase II trial (IFCT0401) evaluated gefitinib as first line treatment in non-resectable P-ADC. Tissue samples were collected for central pathological review and molecular analysis in attempt to determine if an association existed between disease control (DC) by gefitinib and biological markers. Methods: Histologic types were classified according to the 2004 WHO classification as BAC variants and ADC, other types and as non-mucinous or mucinous/mixed. Immunohistochemistry were performed using antibodies against the following proteins: TTF1, Ki67, phosphorylated AKT, erbB2, and EGFR. Polysomy/amplification was examined for erbB2 and EGFR. EGFR 18–21 and K-ras 1 exons were amplified and sequenced. Results: A tissue specimen was collected from 67 of the 88 eligible participants, among which 35 were from surgical resection. This subgroup did not differ from the overall trial population in terms of sex ratio (0.51 vs 0.56), proportion of non-smokers (34 vs 55%) and DC rate (34 vs 29%). Results described herein were obtained in 22 of the 35 surgical specimens collected. Sixteen were BAC variants (73%) and 6 ADC other types. Of the 22, 14 were non-mucinous and 8 mucinous. TTF1, Ki67, P-AKT, erbB2 as well as EGFR expression did not differ between BAC variants and ADC other types. TTF1 and EGFR scores of expression were higher in non-mucinous than in mucinous P-ADC. DC on gefitinib was significantly associated with non-mucinous subtype (p = 0.006), higher TTF1 (p = 0.06) and EGFR (p = 0.07) scores of expression, but not with other markers. K-ras exon-1 codon 12 mutation was found in 6 tumors of which 5 progressed on gefitinib. Polysomy of EGFR was seen in 2 tumors, 1 of which also contained EGFR mutation (exon-19 deletion); both were controlled by gefitinib. Conclusions: Among patients with P-ADC who received gefitinib, non-mucinous subtype, high TTF1 or EGFR score of expression, and EGFR polysomy and/or mutation may have improved DC, while K-ras mutation seems associated with disease progression. [Table: see text]
Maintenance gefitinib (G) after chemoradiotherapy (CRT) in patients (pts) with unresectable stage IIIA/B non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network
Authors: Gray J. R. , Spigel D. R. , Hainsworth J. D. , Vazquez E. , Peyton J. D. , Raefsky E. L. , Malik R. , Marsland T. , Waples J. , Greco F. A. 
Published: March 2020

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N3 mediastinal nodes >4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m2 IV and gemcitabine 800 mg/m2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]