bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of BIBW 2992, a novel irreversible dual EGFR and HER2 tyrosine kinase inhibitor (TKI), in patients with adenocarcinoma of the lung and activating EGFR mutations after failure of one line of chemotherapy (LUX-Lung 2)
Authors: Shih J. , Yang C. , Su W. , Hsia T. , Tsai C. , Chen Y. , Chang H. , Terlizzi E. , Shahidi M. , Miller V. A. 
Published: August 2020

8013 Background: EGFR mutations are associated with exquisite sensitivity to EGFR TKIs in NSCLC. A phase II trial evaluating the efficacy of BIBW 2992 (Tovok), a novel, potent, irreversible, dual EGFR and HER2 TKI with preclinical activity in cell lines harboring activating (H3255, IC50=0.7 nM) and resistant (H1975, IC50=99 nM) EGFR mutations, is reported. Methods: Objective response rate is the primary endpoint of this 2-stage trial. Based on 16 or more unconfirmed PRs in an interim analysis of the first 40 2nd line patients (pts) completing 1 course (28 days), accrual will continue to a total of 120 1st and 2nd line pts (expected completion of accrual by May 2009. Data on 2nd line pts only are presented). Eligible pts have stage IIIB/IV lung adenocarcinoma, EGFR mutation in exons 18–21 (tested by direct sequencing), measurable disease, ECOG PS 0–2 and adequate end organ function. Pts receive 50 mg BIBW 2992 qd until progression. Tumor assessments are performed every 4 weeks for 12 weeks, then every 8 weeks. Results: Since Oct 2007, samples from 289 pts (222 from Taiwan and 67 from the US) have been sequenced. 100 had detectable EGFR mutations including del19 (n=39), L858R (n=45) and others (n=16). 69 pts have started treatment. The trial was moved to stage 2 after 21 of the first 38 treated pts had objective response at 28 days. Of 55 evaluable 2nd line pts, 29 (53%) had PR, and 23 (42%) had SD. Median follow up is 5.1 months. Most common related AEs were diarrhea and skin-related AEs, reported in 87% and 88% of pts, respectively. 27 pts (42.9 %) had dose reduction to 40 mg and 7 pts (11%) to 30 mg but only 1 pt permanently discontinued due to AEs. Diarrhea and rash were main causes of dose reduction. Conclusions: In the 2nd line setting, BIBW 2992 shows efficacy in NSCLC harboring EGFR activating mutations. Diarrhea and skin disorders, the most frequently observed AEs, are manageable with supportive care and dose reduction. Updated response and disease control rates and preliminary progression-free survival data will be presented. An international Phase III trial program investigating BIBW 2992 in NSCLC, LUX-Lung, is now recruiting. [Table: see text]
Italian multicentric trial comparing chemotherapy with or without low-dose interleukin-2 (IL-2) in advanced non-small cell lung cancer: Results from a phase III randomized study
Authors: Ballardini M. , Ridolfi L. , Bertetto O. , Santo A. , Naglieri E. , Lopez M. , Recchia F. , Lissoni P. , Fumagalli L. , Ridolfi R. 
Published: August 2020

8019 Background: Non small cell lung cancer (NSCLC) is associated with an IL-2-dependent cell-mediated immunodeficiency, and lymphocyte count is considered an independent prognostic factor as it seems to correlate with overall survival. A phase III randomized Italian multicentric trial was conducted to evaluate the efficacy of subcutaneous low-dose IL-2 added to standard CT on overall survival (OS) in advanced NSCLC patients. Methods: Histologically/cytologically confirmed stage IIIb or IV non operable NSCLC patients with measurable disease, ECOG PS 0–2, age 18–70 years and adequate bone marrow, renal and liver function were eligible for the study. Randomization was stratified by center, ECOG PS, stage of disease and percentage of weight loss. All patients received gemcitabine (1000mg/m2) on days 1 and 8 + cisplatin (100mg/m2) on day 2 every 21 days for a maximum of 6 cycles (CT arm). In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3–5; 9–11; 15–17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 120 patients per arm. Results: From June 2000 to October 2004, 241 patients were randomized (arm A/B: 127/114). At a median follow up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 logrank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, logrank). Conclusions: The study did not show any relevant difference in clinical outcome by the addition of IL-2 to CT. Safety and subgroup analyses are ongoing to verify the efficacy of IL-2 as a function of clinical and biological characteristics of patients and tumors. Future studies to investigate the role of T-regulators in chemoimmunotherapy strategies, unknown when the study was originally planned, could be conducted. No significant financial relationships to disclose.
Paclitaxel/gemcitabine versus paclitaxel/vinorelbine in advanced non-small cell lung cancer (NSCLC): A phase III randomized study
Authors: Kosmidis P. A. , Timotheadou E. , Koutras A. , Pentheroudakis G. , Christodoulou C. , Dimopoulos A. M. , Bafaloukos D. , Samantas E. , Pectasides D. , Syrigos K. 
Published: August 2020

8038 Background: Paclitaxel and vinorelbine (PV) have shown synergism of cytotoxic effect in vitro (Cancer Invert, 2000, 18(8): 804-5). This combination was compared prospectively to the paclitaxel/gemcitabine (PG) regimen in non-operable NSCLC. Methods: 415 stage IIIb wet and IV chemotherapy-naïve for metastatic disease patients with PS 0–1 were randomized to paclitaxel 200mg/m2 on day 1 plus either gemcitabine 1gm/m2 (Group A) or vinorelbine 25mg/m2 (Group B) on days 1 and 8 every 3 wks as first line chemotherapy. Results: A total of 398 out of 415 patients were eligible for analysis on the intent to treat basis (group A: 196, group B: 202). All patient and disease characteristics were well balanced. Overall response rate (RR) was 27% for group A and 24% for group B (P=0.57). Median progression free survival (PFS) was 5.2 months (m) (95% CI, 4.4 - 5.9) and 4.7m (95% CI, 4.1 - 5.3) for groups A and B respectively (P=0.51). Median survival (OS) was 11.5m (95% CI, 9.5 - 12.6) and 9.3m (95% CI, 7.7 - 10.9) for groups A and B respectively (P=0.25). Grade 3/4 neutropenia was worse (P<0.001) in group B. Febrile neutropenia and severe infections were more prominent (P<0.001, P=0.005 respectively) in group B. Conclusions: Although RR, PFS, OS are similar in both groups, toxicity is significantly worse in group B and therefore further investigation of PV is of no value. No significant financial relationships to disclose.
Preliminary safety and effectiveness of bevacizumab (BV) based treatment in subpopulations of patients (pts) with non-small cell lung cancer (NSCLC) from the ARIES study: A bevacizumab (BV) treatment observational cohort study (OCS)
Authors: Fischbach N. A. , Spigel D. , Brahmer J. , Garst J. , Robles R. , Chung C. , Wang L. , Sing A. , Lynch T. 
Published: August 2020

8040 Background: Phase III trials have shown that bevacizumab (Avastin, BV), an anti-VEGF monoclonal antibody, prolongs progression-free and overall survival in advanced NSCLC pts. To further define clinical outcomes associated with BV treatment among a broader population of NSCLC pts in a real-world setting, the ARIES OCS was initiated. Pt populations in OCSs are often more reflective of pts encountered in practice, permitting examination of treatment benefit and toxicity in subgroups that might be too small for study in traditional randomized controlled trials (RCTs). The NSCLC cohort in ARIES will assess clinical outcomes in the overall cohort as well as subpopulations such as the elderly, pts with poor PS or pts on concurrent anticoagulants (AC). Methods: Pts with advanced NSCLC whose 1st-line therapy includes BV may enroll. 257 sites are enrolling pts; total accrual of 2000 pts is expected. There are no protocol-specified treatments or assessments. Data is collected at baseline (BL) then quarterly, including targeted adverse events (AEs) and BV-related serious AEs. Clinical outcomes will be descriptively summarized by baseline characteristics. Multivariate analyses will be conducted if cohort size is sufficient. Results: As of 9/15/08, 1518 NSCLC pts have enrolled. Median F/U is 7.5 mos. Key BL characteristics: 20% ≥75 yrs; 67% adenocarcinoma; 10% ECOG ≥2; 8% brain metastasis; 5% therapeutic AC. The most common 1st-line chemotherapy regimen was carboplatin/paclitaxel (64%). Key safety outcomes and cohort size of subpopulations are in the Table . Conclusions: The safety of BV in subpopulations of pts in ARIES (elderly pts, pts with ECOG PS ≥2, with brain mets at BL, or on therapeutic AC) is generally consistent with safety results from RCTs. Updated outcomes analyses will be presented at the meeting for >1600 pts and subpopulations. [Table: see text] [Table: see text]
Efficacy of pemetrexed-cisplatin (PC) in East Asian patients (pts): Subgroup analysis of a phase III study comparing PC versus gemcitabine-cisplatin (GC) in first-line treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Orlando M. , Lee J. S. , Yang C. , Simms L. , Park K. 
Published: August 2020

8045 Background: East Asian ethnicity is a recognized favorable prognostic factor in the treatment of NSCLC in trials with either chemotherapy or EGFR tyrosine-kinase inhibitors (TKIs). In a global phase III study (Scagliotti JCO 2008), superior efficacy of PC was shown for pts with nonsquamous NSCLC, while Asian ethnicity was prognostic in the overall population. The purpose of this analysis is to describe the patient and disease characteristics of the East Asian pts enrolled in this study and assess efficacy according to histology and smoking history. Methods: This retrospective analysis of a large phase III study included only patients enrolled from Korea and Taiwan. For survival and progression-free survival (PFS), Cox-adjusted analyses were used to estimate the hazard ratio and 95% CI, while medians were estimated using Kaplan-Meier method. Results: Results for PFS and response rate showed trends similar to overall survival in East Asian pts, favoring PC therapy in nonsquamous pts. The use of post-discontinuation targeted therapies such as EGFR-TKIs was similar between treatment arms in the overall population and in nonsquamous pts. In East Asian pts, EGFR-TKI use was slightly higher in the GC arm, in both the overall population and in nonsquamous pts. In a further subgroup analysis defined by smoking status, East Asian nonsquamous pts treated with PC had longer survival (not statistically significant). Conclusions: Pt and disease characteristics between the East Asian subgroup and the overall population were similar, with notable differences in the percentage of pts with no smoking history and the greater use of EGFR-TKIs as post-discontinuation therapy. This analysis shows the improved efficacy outcomes for East Asian nonsquamous pts treated with PC is consistent with the previously observed treatment effect of PC on nonsquamous NSCLC. [Table: see text] [Table: see text]
Cetuximab combined with either gemcitabine (G) followed by docetaxel (D) or carboplatin/gemcitabine (CP/G) in chemotherapy-naive patients (pts) with advanced non-small cell lung cancer (NSCLC): Safety profile from the ongoing phase II/III GemTax IV trial
Authors: Serke M. , Pilz L. R. , Cicenas S. , Eschbach C. , Fischer J. , Kortsik C. , Schumann C. , Steins M. , Manegold C. 
Published: August 2020

8048 Background: The EGFR-targeting antibody cetuximab is undergoing broad clinical investigation in NSCLC. Our randomized trial assesses the safety of cetuximab combined with 2 different chemotherapy (CT) regimens in pts with advanced NSCLC. Phase II results are reported. Methods: Pts with histologically confirmed stage IIIB or IV NSCLC, WHO PS 0–2, and no prior CT received cetuximab 400 mg/m2 loading dose followed by 250 mg/m2 weekly either combined with G 1000 mg/m2 days 1 + 8 for 2 cycles (3qw) followed by D 75 mg/m2 day 1 for 2 cycles (q3w) (arm A) or CP AUC5 day 1 and G 1200 mg/m2 days 1 + 8 for 4 cycles (q3w) (arm B). Maintenance cetuximab was administered until disease progression or unacceptable toxicity. Results: 229 pts evaluable for safety received 1810 infusions of cetuximab combined with CT and 1216 infusions of maintenance cetuximab. 35 pts in arm A received 1–26 cycles (median 4) of maintenance cetuximab and 6 pts received ≥10 cycles; 50 pts in arm B received 1–22 cycles (median 3) and 7 pts ≥10 cycles. Grade 1 or 2 skin reactions related to study medication occurred in 84% of pts in arm A and 77% in arm B. In general, toxicity was more common in pts receiving CP (leukopenia and neutropenia 10%; pneumonia and fever 10%). In arm B, thrombopenia developed in 14% of pts and allergic reactions in 8%. Toxicities requiring clinical intervention are shown below. Updated results will be presented for 320 pts. Conclusions: Cetuximab does not significantly increase CT toxicity in the induction phase and is well tolerated in the maintenance phase. Notably, ∼75% of pts developed skin rash (grade 3/4 in ∼5% of pts). [Table: see text] [Table: see text]
Efficacy and safety of first-line bevacizumab (Bv) and cisplatin/gemcitabine (CG) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC) in the BO17704 study (AVAiL)
Authors: Leighl N. B. , Zatloukal P. , Mezger J. , Ramlau R. , Archer V. , Moore N. , Reck M. 
Published: August 2020

8050 Background: AVAiL, an international, placebo-controlled, phase III trial, evaluated Bv plus CG in pts with previously untreated advanced, non-squamous NSCLC, with performance status 0/1. A retrospective analysis was performed to assess the efficacy and safety of Bv plus CG in the subpopulation of elderly pts (≥65 years [yrs]). Methods: 1,043 pts (age 20–83) were randomized to C 80mg/m2 and G 1,250mg/m2 q3w for up to 6 cycles plus either Bv 7.5mg/kg q3w (Bv 7.5; n=345), Bv 15mg/kg q3w (Bv 15; n=351) or placebo (Pl; n=347). Bv/Pl was administered until disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (RR) and safety. Efficacy and safety were compared between pts <65 yrs vs ≥65 yrs. Results: Efficacy data were available for 304 pts ≥65 yrs (median age 68), and 739 pts <65 yrs (median age 55). Baseline characteristics were similar between the groups. In the Bv arms, 179 pts (93%) received ≥1 cycle of treatment; 85 (47.5%) completed >6 cycles. Bv-treated pts ≥65 yrs derived an improvement in PFS compared to Pl (Bv 7.5: HR 0.71, p 0.023; Bv 15: HR 0.84, p= 0.25). ORRs were 40%, 29% and 30% for pts ≥65 in the Bv 7.5, Bv 15 and Pl arms. Survival was similar in all treatment arms regardless of age, (pts ≥65 Bv 7.5 HR 0.84; Bv 15 HR 0.88, p=NS). Safety data were available for 284 pts ≥65 yrs and 702 pts <65 yrs. There were no safety signals of concern in older patients. Grade ≥3 toxicities occurred in 84%, 80% and 80% of older pts treated with Bv 7.5, Bv 15 and Pl. Pts ≥65 yrs had no episodes of severe hemoptysis, but in Bv 7.5 and Pl arms, were more likely to have other bleeding, compared to pts <65. The incidence of hypertension and febrile neutropenia were similar in pts ≥65 and <65 yrs. Treatment-related deaths were not increased in Bv-treated pts ≥65 yrs vs pts <65 yrs or in Bv-arms vs Pl. Conclusions: The PFS benefit from Bv-based treatment in the elderly subpopulation is similar to that observed in the overall patient population. No particular safety signals were identified in this population, suggesting acceptable tolerability of Bv in elderly pts in AVAiL. [Table: see text]
Phase II randomized trial of erlotinib versus vinorelbine in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) aged ≥70 years in Taiwan
Authors: Chen Y. , Tsai C. , Shih J. , Perng R. , Whang-Peng J. 
Published: August 2020

8051 Background: Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors, such as erlotinib, are effective against NSCLC, especially in East Asian patients. Single-agent chemotherapy, such as vinorelbine, is an appropriate treatment choice for elderly patients. Oral vinorelbine is more convenient for elderly patients than intravenous vinorelbine. The primary objective of this study was to compare the response rate of chemo-naïve, elderly patients with advanced NSCLC treated with daily erlotinib versus oral vinorelbine. Methods: Chemo-naïve Taiwanese patients aged ≥70 years with advanced NSCLC were enrolled and randomized (stratified by histology, smoking status, ECOG performance status, and gender) to receive either oral erlotinib 150mg/day or oral vinorelbine (60mg/m2 on days 1 and 8 of the first cycle and subsequently increased to 80mg/m2 every 3 weeks in the absence of grade 2 adverse events). From February 2007 to July 2008, 116 patients were enrolled. Results: By October 2008, 77 enrolled patients (n = 37 for erlotinib; n = 40 for vinorelbine) had completed 6 cycles of study treatment and were available for efficacy and safety analyses. Objective response rates were 21.6% (8/37) with erlotinib and 12.8% (5/39) with vinorelbine [95% CI -0.09–0.24 for the difference in response rate between arms]. Disease control rate was 70.3% with erlotinib and 56.4% with vinorelbine [95% CI -0.09–0.34 for the difference in disease control rate between arms; p = 0.216). Median time to disease progression was 4.4 months [95% CI 4.1–5.4] with erlotinib, compared with 3.9 months [95% CI 2.4–6.9] with vinorelbine, p = 0.6069. The most common treatment-related toxicities were skin rash and diarrhea with erlotinib, and diarrhea and nausea with vinorelbine. Conclusions: Erlotinib is effective and well tolerated compared with oral vinorelbine in elderly, chemo-naïve, Taiwanese patients with NSCLC. Updated efficacy and safety data will be presented. [Table: see text]
Randomized phase II study of gefitinib alone or with simvastatin in previously treated advanced non-small cell lung cancer (NSCLC)
Authors: Han J. , Lee S. , Yun T. , Moon Y. , Park I. , Kim H. , Lee J. 
Published: August 2020

8057 Background: Statins reduce not only serum cholesterol levels but also mevalonate synthesis by inhibiting HMG-CoA reductase. Mevalonate is a precursor of several cellular major products including dolichol, geranylpyrophosphate (GPP) and farnesyl-pyrophosphate (FPP). Dolichol has a stimulatory effect on DNA synthesis and is linked to several tumor cell proteins. GPP and FPP cause isoprenylation of Ras and Rho those regulate signal transduction of several membrane receptors crucial for cell proliferation, differentiation, and apoptosis, which result in resistance to gefitinib. Thus depletion of mevalonate metabolites may enhance gefitinib activity in NSCLC. This study compared gefitinib alone with gefitinib plus simvastatin in patients with recurrent NSCLC after at least one chemotherapy. Methods: Between May 2006 and September 2008, 107 patients (51% male, 74% adenocarcinoma, 50% never-smoker, 54% more than two prior regimens) were randomly assigned to gefitinib alone (250 mg/d orally, n=53) or gefitinib plus simvastatin (250mg/d and 40 mg/d orally, respectively, n=54). A cycle was considered as 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicities. The primary end point was to assess response rate. Secondary end points included time to progression and survival. Median follow-up was 10.1 months. Results: Efficacy was similar for gefitinib and gefitinib plus simvastatin groups. Objective tumor response rates (RR) were 31.5% (95% CI, 19.1 to 43.9) and 32.1% (95% CI, 19.5 to 44.7); median PFS were 1.9 and 2.0 months; and median OS were 9.5 and 12.7 months, respectively. In subgroup analysis, gefitinib plus simvastatin showed a trend for higher RR than gefitinib alone in non-adenocarcinoma group (38.5% vs. 7.7%, p=0.08). Adverse events at both arms were generally mild (grade 1 or 2) and consisted mainly of skin reactions. Conclusions: Gefitinib combined with simvastatin did not improved efficacy compared to gefitinib alone in this unselected patient population, but showed a trend for higher efficacy in non-adenocarcinoma patients. Although it is preliminary, gefitinib combined with simvastatin showed slightly increased OS. Updated survival data will be presented. No significant financial relationships to disclose.
Everolimus, an mTOR inhibitor, in combination with docetaxel for recurrent/refractory NSCLC: A phase I study
Authors: Khuri F. R. , Harvey R. D. , Saba N. F. , Owonikoko T. K. , Kauh J. , Shin D. M. , Sun S. Y. , Browning K. M. , Tighiouart M. , Ramalingam S. S. 
Published: August 2020

8060 Background: The mammalian target of rapamycin (mTOR) pathway is a key cell-signaling cascade that is aberrantly activated in non-small cell lung cancer (NSCLC). Everolimus (E), an mTOR inhibitor, is active as monotherapy for advanced NSCLC. Based on preclinical synergy between everolimus and docetaxel (D), we conducted a phase I and feasibility study with the combination. Methods: Patients with stage IIIB/IV NSCLC, progression following prior platinum-based chemotherapy and ECOG performance status (PS) of 0–2 were eligible. Sequential cohorts of patients were treated with increasing doses of D (day 1) and E (PO QD, days 1–19). Treatment cycles (C) were repeated every 3 weeks. A standard ‘up and down’ dose escalation scheme was utilized. The primary endpoint was determination of optimal dose of the two agents that can be administered in combination. Results: Twenty three patients were enrolled. Median age - 62 yrs; Females- 11; ECOG PS: 0–6; 1 -16; # of prior regimens: 1–12, 2–6, ≥3 -5. At dose level 1 (D- 60 mg/m2, E- 5mg), none of 6 patients had DLT. Four out of 12 patients at dose level 2 (D-75 mg/m2, E-5 mg) had fever with gr 3/4 neutropenia during cycle 1. At dose level 3 (D- 75 mg/m2, E- 7.5 mg), 2 of 3 pts had DLT (fever with neutropenia and grade 3 mucositis). Pharmacokinetic (PK) sampling was performed on days 1 (n=14), 8 (n=9), and 15 (n=10) of cycle 1. Mean E half-life (hr) on days 1, 8, and 15 were 9.66 (2–14), 12.6 (2.2–21.1), and 14.8 (2–21.2), respectively. E accumulation occurred and was greater than expected. In contrast to the mean predicted accumulation factor (R) based on AUC of 1.22 (1–1.44), actual R on day 8 and 15 were 1.78 (0.72–3.17) and 1.88 (0.37–3.3) respectively. Among 20 pts. evaluable for response, 1 had a partial response and 10 had disease stabilization. Six patients completed 6 cycles of combination therapy and continued on E as maintenance. Conclusions: The recommended doses of docetaxel and everolimus that can be administered as a combination are 60 mg/m2 and 5 mg PO QD respectively. The PK characteristics of everolimus appear unaffected by co-administration with docetaxel. Promising anti-cancer activity was noted with clinical benefit in 55% of the pts. A phase II study has been initiated with the combination in refractory NSCLC. Supported by NCI 5 P01 CA116676. [Table: see text]