bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective trial with preoperative gefitinib to correlate lung cancer response with EGFR exon 19 and 21 mutations and to select patients for adjuvant therapy
Authors: Kris M. G. , Pao W. , Zakowski M. F. , Ladanyi M. , Heelan R. T. , Schwartz L. , Zhao B. , Venkatraman E. , Rusch V. , Rizvi N. A. 
Published: March 2020

7021 Background: Induction therapy provides a unique opportunity for the objective assessment of therapies in patients with NSCLC to facilitate care and advance research. We designed this 40 patient prospective trial to measure gefitinib’s ability to induce regressions preoperatively in individuals with NSCLC and to simultaneously correlate response with mutations in EGFR exons 19 and 21. Patients with ‘in-vivo‘ gefitinib sensitivity and/or mutations receive gefitinib postoperatively as well. To facilitate our goals, we enriched the population studied to select individuals with tumors more likely to harbor mutations in EGFR. Methods: At diagnosis, patients with stage I or II NSCLC had baseline chest CT imaging and a core-needle biopsy to detect EGFR mutations. All participants smoked cigarettes ≤ 10 pack years and/or had tumors with bronchioloalveolar features. All received gefitinib 250 mg daily. After 21 days, CT imaging was repeated and resection followed. Surgical specimens were agained assayed for EGFR mutations. Patients with mutation and/or a ≥ 25% regression (WHO) were given gefitinib 250 mg for 2 years. Results: 20 patients enrolled to date. EGFR mutations were detected in both pre and post gefitinib specimens in 4/19 tested (21%). Five of 19 (26%) had a ≥ 25% bidimensional tumor reduction after 3 weeks. Regressions ≥ 25% were seen in 2/4 (50%) with exon 19 and 21 EGFR mutations and 3/15 (20%) with WT EGFR. The other 2 patients with mutations had 11% and 23% tumor regressions. The 6 patients who had either a ≥ 25% lesion reduction and/or mutation received gefitinib postoperatively. No perioperative complications related to gefitinib occurred. All patients are relapse free. Conclusions: In this ongoing trial, 1) Our ‘enrichment strategy‘ resulted in the detection of twice the expected number of EGFR mutations in USA patients with NSCLC. 2) Gefitinib sensitivity can be assessed by CT in 3 weeks. 3) Results of mutation detection were identical in pre- and post-treatment specimens. 4) The rate of response is numerically higher in patients with EGFR mutations in exons 19 and 21. 5) We are using the surgical specimens to elucidate determinants of gefitinib sensitivity in the absence of EGFR mutation. Support: CA05826, CA113653. [Table: see text]
Prospective correlative assessment of biomarkers in E4599 randomized phase II/III trial of carboplatin and paclitaxel ± bevacizumab in advanced non-small cell lung cancer (NSCLC)
Authors: Dowlati A. , Gray R. , Johnson D. H. , Schiller J. H. , Brahmer J. , Sandler A. B. 
Published: March 2020

7027 Background: E4599 was a phase II/III trial, in which 878 patients with advanced NSCLC were randomized to carboplatin + paclitaxel (PC arm) or PC + bevacizumab (PCB arm). Survival and progression free survival (PFS) were superior on the PCB arm (Sandler, ASCO 2005). The rationale for markers used in this correlative study were based on elevated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (ICAM) in NSCLC and changes in response to endothelial apoptosis. Methods: Prospective laboratory correlates included measurements of pretreatment plasma VEGF as well as pretreatment and week 7, bFGF, ICAM, and E-Selectin. 166 patients had pre- and 112 had post-treatment measurements. Measurements were made by ELISA. Low and high levels were defined as ≤ or > than the median. Results: There were significant associations between E-Selectin and ICAM (p = .003) and between bFGF and VEGF (p = .01). E-Selectin (p = .01) and bFGF (p = .004) showed significant decreases from baseline at week 7 in both arms (Wilcoxon signed-rank tests). Only baseline ICAM showed a significant association with response. Patients with low baseline ICAM in both arms had a higher response rate of 29% vs 13% in high ICAM group (p=0.03, Fisher’s exact test). Patients with low baseline ICAM levels had a significantly better overall survival (p=0.00005) compared to patients with high ICAM levels as well as a better 1-year survival (65% vs 25%). No other factor predicted survival. Tests for treatment by factor interactions, which test whether the effect of treatment (the addition or not of bevacizumab) is different within the low and high levels were significant only for baseline ICAM where treatment interaction is significant for PFS (p=.04). This suggests a benefit from bevacizumab (53% reduction in the PFS hazard rate) in the group with low baseline ICAM levels vs no benefit from bevacizumab for patients with high levels. Conclusions: Baseline ICAM levels are strongly prognostic for survival and response to chemo. This exploratory correlative study suggests that improvements in PFS from the addition of bevacizumab occur mainly in patients with low baseline ICAM levels. [Table: see text]
Low dose spiral computed tomography for early diagnosis of lung cancer. Results of baseline screening in 5,000 high-risk volunteers
Authors: Veronesi G. , Bellomi M. , Spaggiari L. , Pelosi G. , Maisonneuve P. , Paganelli G. , De Fiori E. , Leo F. , Rotmensz N. , Veronesi U. 
Published: March 2020

7029 Background: The high lethality of lung cancer is related to the advanced stage at diagnosis. Early studies have demonstrated that screening with CT is effective to diagnose lung cancer at earlier stage but the optimal clinical approach for the management of patients identified with nodules during screening has yet to be defined. We report the first-year results of our CT screening trial. Method: Between October 2004 and October 2005, 5,189 asymptomatic current or former smokers of more than 20 packs/year, older than 50 years, were enrolled in a single-institution screening trial using annual low-dose multidetector CT for 5 years. A protocol for the diagnostic work-up of nodules identified by CT was LD-CT at 1 year for nodules with maximum diameter less than 5 mm, LD-CT at 3 months for lesions between 5.1 and 8 mm and FDG-PET for lesions larger than 8.1 mm. Trans cutaneous biopsy was not routine part of this protocol. End-points were: prevalence and incidence rates of lung cancer, stage distribution, resectability, recall rate and invasive procedure for benign disease. Results: Median age of volunteers was 57 years, 66% were males and 80% current smokers. The prevalence of lung cancer diagnosed at first CT was 1.0% (54 cases; 65% stage I; 9% stage II; 22% stage III and 4% Stage IV). Forty-seven tumors (87%) were radically resected (45 lobectomies, 1 pneumonectomy, 1 atypical segmentectomy). Major surgical morbidity and mortality were 4% and 2% respectively. Recall rate was 10%. Seven patients (1.3% of all recalled subjects) underwent surgical diagnostic procedures for non-malignant disease representing 12% of all screening surgical procedures versus 16% in a non-screening control group treated in the same unit and period. Conclusions: Our results confirmed that screening with low-dose CT allows the detection of early stage lung cancer in a high proportion of cases increasing the probability of cure. Although follow-up is necessary to confirm the efficacy of the proposed work-up protocol, the initial results are promising, with a very low number of invasive procedures performed for benign lesions. No significant financial relationships to disclose.
Adding oral talactoferrin to first-line NSCLC chemotherapy safely enhanced efficacy in a randomized trial
Authors: Wang Y. , Raghunadharao D. , Raman G. , Doval D. , Advani S. , Julka P. , Parikh P. , Patil S. , Nag S. , Madhavan J. , Varadhachary A. 
Published: March 2020

7095 Background: Talactoferrin alfa (TLF) is an oral immunomodulatory protein with a novel mechanism. TLF showed preclinical anti-cancer activity alone and in combination with chemotherapy. In Phase I/II trials, TLF was safe with apparent single-agent anti-cancer activity in non-small cell lung cancer (NSCLC). Methods: 110 chemo-naive patients with advanced or metastatic NSCLC were randomized (1:1) in a multi-center trial to carboplatin/paclitaxel (C/P) therapy plus either TLF or placebo. Starting the day after C/P (C:AUC 5 mg/mL/min; P:175 mg/m2) in chemo-cycles 1, 3 and 5, oral TLF (1.5 g BID) or placebo was administered in 35-day cycles for up to three cycles or until progression. Primary endpoint was Confirmed Response Rate (RR; PR+CR) by CT using RECIST. Secondary endpoints included Progression Free Survival (PFS) and Overall Survival (OS). Results: Baseline patient and disease characteristics were comparable in both groups. All 110 patients were included in the Intent To Treat (ITT) population. 100 patients with at least one CT scan after starting treatment were prospectively defined as the Evaluable population. Adding oral TLF to C/P enhanced efficacy on all endpoints examined including RR, PFS and OS. Confirmed RR in the 100 evaluable patients significantly increased from 29% to 47% (P = 0.05). Confirmed RR in the 110 ITT patients improved from 27% to 42% (P = 0.08). Median PFS in both evaluable and ITT patients improved by 2.8 months (67%). Median OS improved by 31% and 18% in evaluable and ITT patients, respectively. A landmark analysis comparing survival in patients with and without a PR showed a significant difference (P < 0.01), suggesting a strong association between RR and survival. TLF appeared to be very safe and well tolerated with no drug-related SAEs. Fewer AEs were observed in the TLF arm than in the placebo arm, 346 and 432 AEs, respectively (P = 0.0023). The number of Grade 3/4 AEs was also lower in the TLF arm, 60 versus 91 (P = 0.0144). Conclusions: Adding oral TLF to standard C/P chemotherapy in NSCLC was safe and increased efficacy in a randomized, multi-center, double-blind, placebo-controlled trial, with apparent improvements in RR, PFS and OS. Results with TLF compare favorably to other anti-cancer agents. Oral TLF will be further evaluated in a Phase III trial. [Table: see text]
Randomized phase II study of gemcitabine-oxaliplatin or gemcitabine-cisplatin in chemonaive patients with advanced non-small cell lung cancer (NSCLC)-CLEO 05
Authors: Le Chevalier T. , Thezenas S. , Breton J. , Pujol J. , Coudert B. , Sun X. , Laza M. , Quoix E. , Schott R. , Geneve J. 
Published: March 2020

7097 Background: Gemcitabine-cisplatin is one of the reference doublets used in NSCLC. Oxaliplatin is a platin analog which offers a promising efficacy/tolerance profile in NSCLC. The combination of gemcitabine and oxaliplatin has been proven feasible and active in solid tumors. Methods: Patients with chemonaive, measurable, PS 0 or 1, stage IIIB/ IV NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 day 1 & 8 plus oxaliplatin 130 mg/m2 day 1 (GEMOX) or gemcitabine 1,250 mg/m2 day 1 & 8 plus cisplatin 80 mg/m2day 1 (GEMCIS). Cycles were given every 3 weeks. The primary endpoint of the study was the response rate according to the RECIST criteria. Secondary endpoints included tolerance, survival and quality of life. Results: Between October 2003 and December 2004, 130 patients (66 in GEMOX and 64 in GEMCIS) were accrued at 12 centres. Baseline patient characteristics were similar in the 2 groups. Mean age was 61. There were 96 males and 34 females; 27% of patients were PS 0 and 73% were PS 1; 15% had stage IIIB and 85% had stage IV. Median number of cycles was 5 in each group. Objective response rates were 36% in GEMOX (CI 95%: 25%-50%) and 39% in GEMCIS (CI 95%: 28%-54%) respectively. Time to progression was 173 days in the GEMOX group and 163 days in the GEMCIS group. Median survival was 10.8 months in the GEMOX group and 10.4 months in the GEMCIS group. Grade III/IV neutropenia was observed in 38% of patients after GEMOX and 41% after GEMCIS; thrombocytopenia was observed in 40% and 33% of cases respectively. Grade 2+ neurotoxicity was more frequent after GEMOX (18% vs 3%). Conclusions: GEMOX has an activity comparable to GEMCIS and may be an alternative for those patients with advanced NSCLC who have a contra-indication to cisplatin. [Table: see text]
Final results of a phase II trial of bexarotene capsules as 3rd or subsequent line therapy in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Govindan R. , Crowley J. , Schwartzberg L. , Kennedy P. , Williams C. , Ekstrand B. , Sandler A. , Jaunakais D. , Ghalie R. 
Published: March 2020

7099 Background: Bexarotene, a rexinoid that binds to RXR nuclear receptors, has antiproliferative, differentiating, and apoptotic effects. Phase II studies of bexarotene plus chemotherapy in previously untreated NSCLC suggested improved patient survival. This study evaluated bexarotene for relapsed advanced NSCLC. Methods: Patients were eligible if they had NSCLC Stage IIIB wet/IV, had failed ≥ 2 prior systemic therapies, had previously received a taxane and platinum, had ECOG performance status (PS) 0–2, and had adequate organ function. Bexarotene 400 mg/m2 daily plus prophylactic levothyroxine and a lipid-lowering agent were given until disease progression or unacceptable toxicities occurred. The primary efficacy endpoint was survival. To detect a 50% increase in median survival from 4 months, as shown with 3rd line chemotherapy, to 6 months, 125 evaluable patients were required for a 90% power at a 1-sided 5% significance. Results: A total of 146 patients were enrolled at 32 sites. Median age = 66 (range, 34–87), male = 51%, PS 2 = 23%, adenocarcinoma = 54%, and median prior therapies = 3 (range 1–7) with 55% having failed gefitinib. Bexarotene was usually well tolerated and there were no therapy-related deaths. For the 124 patients who were treated for at least 14 days and were considered evaluable for efficacy, median and 1-year survival were 6 months and 25%, respectively. Baseline albumin < 3 g/dL and PS = 2 were significantly associated with shorter survival. For 26 patients who developed hypertriglyceridemia plus skin rash by Day 21, median and 1-year survival were 12 months and 44%, respectively, vs. 2 months and 12% in 36 patients with neither (p = 0.0003). Partial response was reported in 1 patient. When assessed by FACT-G, quality of life was improved or stabilized in 65% of patients. Conclusions: Survival of patients with heavily pretreated NSCLC may be extended with oral bexarotene therapy. Confirmation of these results with a randomized trial is warranted. Ongoing investigations attempt to explain the notable outcome reported in this and other bexarotene trials in the subset of patients who developed hypertriglyceridemia with or without skin rash. [Table: see text]
Efficacy and safety of patupilone in non-small cell lung cancer (NSCLC): A phase I/II trial
Authors: Sánchez J. M. , Mellemgaard A. , Perry M. , Zatloukal P. , Hamm J. , Belani C. P. , Kim E. , Felip E. , Berton M. , Johri A. 
Published: March 2020

7104 Background: Based on its activity in a wide range of tumors including those that are taxane resistant, the novel microtubule stabilizer patupilone (EPO906; epothilone B) has the potential to treat NSCLC. Fifty patients were enrolled in phase I to evaluate safety, efficacy, and optimal dose. The phase II part of this study is investigating the antitumor activity of patupilone in 53 patients with stage IIIB/IV NSCLC. Methods: Patients with histologically or cytologically confirmed unresectable, locally advanced, or metastatic NSCLC documented before 1st-line therapy without symptomatic or uncontrolled brain metastases received patupilone at a starting dose of 10.0 mg/m2 q3wk by 20-minute IV infusion. Additional inclusion criteria: age ≥18 years; WHO performance status 0–1; prior treatment with a platinum-containing regimen. Primary objective of the phase II, single-arm, 2-stage, multicenter trial: to determine activity of patupilone q3wk (overall response using modified RECIST) in NSCLC. An additional cohort with recurrent brain metastases from NSCLC is being accrued to evaluate safety, pharmacokinetics, and activity. Results: In phase I, all patients received prior treatment with platinum therapy; 28% had received taxanes and 78% nontaxanes. Patupilone dose was escalated from 6.5 to 13.0 mg/m2 q3wk. Dose-limiting toxicities occurred in 4 patients: 1 with grade 3 asthenia and 3 with grade 3 diarrhea at various dose levels. The most frequent adverse events (AEs) were diarrhea (66%), nausea (40%), vomiting (34%), paraesthesia (32%), abdominal pain (30%), and fatigue (30%). The most frequent grade 3 AE was diarrhea (14%); a grade 4 AE (asthenia) occurred in 1 patient. Overall phase I response: 5 PR, 16 SD, and 26 PD. Based on risk-benefit analyses, 10.0 mg/m2 q3wk was recommended as the phase II dose. Phase II is ongoing: 25 of 53 patients (15 men and 6 women with NSCLC; 2 men and 2 women with brain metastases) have been enrolled. Conclusions: In phase I, patupilone q3wk was safe and well tolerated, with antitumor activity in patients with advanced pretreated NSCLC. Data from phase II will be available at time of presentation. [Table: see text]
Front line therapy with gemcitabine(G) administered immediately prior to pemetrexed (P) for patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC): Final report of a phase II clinical trial
Authors: West H. J. , Belt R. J. , Wakelee H. A. , Monberg M. J. , Frye L. A. , Ye Z. , Obasaju C. K. 
Published: March 2020

7116 Background: P and G have well demonstrated, single-agent activity in pts with locally advanced or metastatic NSCLC. This phase II study was designed to determine the activity of the combination of PG when G was administered immediately prior to P on day 8 of a 21-day cycle. Methods: Pts with Stage IIIB/IV NSCLC were enrolled. Treatment was G 1250 mg/m2 on D 1 and 8, with P 500 mg/m2 on D 8, immediately following G. Treatment was repeated every 21 days for 6 cycles. Pts received folic acid, vitamin B12 and steroid prophylaxis. Results: 54 pts (32 M/22 F) were enrolled in the study. Median age was 65.0 (range = 43 - 87) years, ECOG PS 0: 1 = 35.2%: 57.4%; Stage IIIB (9.3%), Stage IV (90.7%); Histology: adeno (61.1%) squamous (18.5%), and large cell (5.6%). Median dose intensity was 83.2% for P and 82.2% for G. Grade 3 toxicities were neutropenia (12.0%), thrombocytopenia (8.0%), dyspnea (16.0%), febrile neutropenia (10.0%), anemia (4.0%), fatigue (18.0%), nausea (10.0%), vomiting (8.0%), and rash (2.0%). Grade 4 toxicities were neutropenia (28%), thrombocytopenia (4%), dyspnea (6%), anemia (0%), fatigue (4%), nausea (0%), vomiting (0%), rash (0%). Five patients (10%) experienced Grade 1 alopecia. Median TTPD was 4.4 months and survival was 10.6 months. There were 0 CR, 16 PR (35.6%), 16 SD (35.6%), and 12 PD (26.7%), for an overall best response rate of 35.6%. Conclusions: In this study, PG had a disease control rate (ORR + SD) of 71.1% in the front-line treatment of NSCLC, suggesting that this is an active doublet. Administering P on D 8 rather than D 1 did not seem to negatively impact the therapeutic index. [Table: see text]
Phase II trial of cisplatin (C), etoposide (E) and radiation (RT) followed by gemcitabine (G) vs G and docetaxel (D) in stage III A/B unresectable non-small cell lung cancer (NSCLC)
Authors: Movsas B. , Langer C. , Wang L. H. , Jotte R. M. , Xu F. , Huang C. , Hood K. E. , Ye Z. , Monberg M. , Obasaju C. K. 
Published: March 2020

7120 Background: SWOG 9504 demonstrated the benefit of D consolidation after E + C with radiation therapy in pts with locally advanced NSCLC. This study was developed to assess the feasibility and efficacy of consolidation with either G alone or with D after the same chemoradiation schedule as SWOG 9504. Methods: The treatment schema included concurrent C 50 mg/m2 Day 1, 8 + E 50 mg/m2 Day 1–5 for two 28-day cycles + RT 180 cGy daily for 7 weeks after which pts were randomized to consolidation treatment of either G 1000 mg/m2 Day 1, 8 (Arm A) or G 1000 mg/m2 Day 1, 8 + D 75 mg/m2 Day 1 (Arm B) every 21 days for 3 cycles. Forty-six pts have been accrued; data is currently available in 28. Conclusions: Preliminary data indicate that G or G + D following chemoradiation in locally advanced NSCLC is well tolerated. The doublet, as expected, results in more toxicity, particularly myelosuppression and fatigue. Response, survival and TTP data will be presented at the time of the meeting. [Table: see text] [Table: see text]
Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small cell lung cancer: An analysis of the Spanish Lung Cancer Group pharmacogenomic study of cisplatin and docetaxel combination (PLATAX)
Authors: Camps C. , De Las Peñas R. , López-Vivanco G. , Garde J. , Sanchez J. , Viñolas N. , García-Gómez R. , Barón S. , Terrasa J. , Pujol E. 
Published: March 2020

7124 Background: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. Methods: We analysed data of 493 patients who received chemotherapy (cisplatin and docetaxel) within the pharmacogenomic, open-label, single-arm, multicentric PLATAX trial. Three subgroups of patients were considered: global population, patients who received at least three cycles of chemotherapy, and those who received at least six cycles. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). Relative dose intensity was analysed for both drugs. The primary endpoint was overall survival. Results: Median overall survival was 9 months (8.2–9.7). Median relative dose intensity was 0.97 for cisplatin and docetaxel. 403 patients received at least three cycles of chemotherapy, and 255 received six or more. Neutropenia appeared in 172 patients (30.8%), 72 of them G3–4 (18.6%). Dose intensity was lower in patients who presented any grade of neutropenia versus those without neutropenia in the three analyzed subgroups, for both drugs (p < 0.05). Factors associated with higher risk of death were ECOG 1–2 (HR 1.8, p = 0.00) and female (HR 1.5, p = 0.02). There were no differences in overall survival between patients with G0 vs G1–2 vs G3–4 neutropenia (8.7 vs 11.6 vs 9.6 m, p = 0.41), however the risk of death was lower in patients with ECOG 0, that presented neutropenia (HR: 0.545, IC 95%: 0.31, 0.96; p = 0.034). Conclusions: Neutropenia during chemotherapy may be associated with increased survival of patients with advanced non-small cell lung cancer and ECOG 0. Its absence is not a result of underdosing. Prospective trials are needed to assess whether neutropenia could be a biological measure of drug activity and a marker of efficacy. No significant financial relationships to disclose.