bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy study of metronomic chemotherapy in metastatic NSCLC.
Authors: Srinivas B. J. , Radheshyam Nayak , Gunasagar C. , Govind Eriat , Vidya Veldore H. , Raghavendra Rao M. , Kamat Mangesh , Siddartha Roy 
Published: March 2020

e19092 Background: Metastatic lung cancer patients are at best treated palliatively. We evaluated the effects of metronomic chemotherapy on survival outcomes in this population. Methods: Thirty four subjects with treatment refractory (n=26) and treatment naive (n=7) metastatic lung cancer were included in a open label single arm efficacy study of metronomic chemotherapy. Patients were given a chemotherapy regimen of Tab. Cyclophsophamide 50 mg once daily and cap. etoposide 50 mg once daily, 3 weeks on and one week off in 28 day cycle over a minimum period of 3 months or until the progression of their disease whichever was earlier. Patients were assessed for treatment response using RECIST criteria (version 1.1) and duration of progression free survival and overall survival. Data were analysed using Kaplan Meier survival analysis. Results: The mean age of the study population was 63.4 ±11.2 years. The mean duration of metronomic chemotherapy was 94.9 ±60.4 days. Overall 64.7% had progressive disease and 26.5% had stable disease. There was a significant improvement in overall survival in those with ECOG performance status of 1 compared to ECOG status of 2 (median survival =240 vs.52 days, Log Rank Mantel Cox =11.32, p=0.001) and pathology grade 2 compared to grade 3 (median survival =200 vs. 37 days, Breslows Wilcoxon =5.76, p=0.02) and stable disease on RECIST compared to progressive disease following metronomic chemotherapy (Median survival =360 vs. 50 days, Log Rank Mantel Cox =8.68, p=0.003). There was also a significant improvement in progression free survival in those with ECOG performance status of 1 compared to ECOG status of 2 (median survival =98 vs. 52 days, Log Rank Mantel Cox =6.62, p=0.001) and in grade 2 compared to grade 3 disease (mean survival =97 vs.32 days, Log Rank Mantel Cox =4.73, p=0.03). Tumor load and multiple organ sites of disease did not seem to influence survival. Conclusions: The results suggest stable response in about one third of study population, favorable progression free and overall survival rates following metronomic chemotherapy. Performance status is important predictors in this category of population.
EML4-ALK mutation in Austrian patients with NSCLC: A multicenter study.
Authors: Hochmair Maximilian J. , Setinek Ulrike , Efstathiades Thomas , Kirchbacher Klaus , Mohn-Staudner Andrea , Arns Britt-Madeleine , Gulesserian Melina , Dworan Nina , Breyer Marie , Patocka Kurt , Burghuber Otto 
Published: March 2020

e19093 Background: EML4 (echinoderm microtubule-associated protein-like 4) - ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase, an oncoprotein found in a subgroup of non-small-cell lung cancer (NSCLC) predicts the response to ALK inhibitors. In general, AML4-ALK mutation is found in 2 to 7% of Caucasian patients with NSCLC and occurs more often in never and former smokers, adenocarcinomas, and younger, male patients. However, the frequency of EML4-ALK mutation in Austrian patients with NSCLC is unknown. The aim of the study was to evaluate the prevalence of EML4-ALK mutation in Austrian patients with NSCLC. Methods: From September 2011 to October 2012 tumour tissue from bronchoscopy, CT- and ultrasound guided biopsies and surgical specimen with histological type of adenocarcinoma and NSCLC NOS (Not Otherwise Specified) excluding squamous cell carcinoma, large cell carcinoma and neuroendocrine carcinoma were analysed for EML4-ALK mutations from 4 hospitals in Austria with high expertise in the management of lung cancer. Mutation detection was performed with a two-step procedure. First an immunhistochemical staining was done (ALK confirm/Ventana) and further on positive cases were tested by ALK FISH (dual colour breakapart FISH/Abbott Vysis). Results: In total 639 patients were analysed. EML4-ALK positive immunohistochemical staining was found in 35 patients (5,48%). 14 of these patients (2,19%) showed positive ALK FISH analysis. Conclusions: Frequency of EML-ALK mutations in Austrian patients with NSCLC was similar to other Caucasian peers.
Antimetastatic activity of ganetespib: Preclinical studies and assessment of progressions due to new lesions in the GALAXY-1 NSCLC trial.
Authors: Proia David A , Nagai Masazumi , Jimenez John-Paul , Zhang Chaohua , Sang Jim , Guo Wei , Beebe Kristin , Lee Min-Jung , Sequeira Manuel , Smith Donald , Acquaviva Jaime , He Suqin , Trepel Jane B. , Neckers Len , Bahcall Safi R. , Vukovic Vojislav M. 
Published: March 2020

e19097 Background: Heat shock protein 90 (Hsp90) maintains the stability and activity of numerous signaling proteins involved in metastasis including FAK (tumor cell adhesion), MET and MMP9 (cell motility), VEGFR and PDGFR (angiogenesis), and HIF-1α (metabolism, proliferation, motility, angiogenesis). In the GALAXY–1 trial in advanced non-small cell lung cancer (NSCLC) patients, docetaxel (D) plus ganetespib (G), an Hsp90 inhibitor, showed encouraging improvement in overall survival compared to D alone. We evaluated the antimetastatic activity of ganetespib in preclinical models, and compared radiological disease progression due to new lesion formation in the two arms of the GALAXY–1 trial. Methods: Effects of ganetespib were investigated on the: (1) migration of cancer cells under normoxic and hypoxic conditions via scratch assay, (2) expression of metastatic signaling factors using immunoblotting and reverse phase array, (3) architecture of NSCLC tumor xenografts including micro-vasculature, hypoxia, and apoptosis by immunostaining, and (4) metastasis to the lung in both tail vein and orthotopic breast cancer in vivo mouse models. In the GALAXY–1 trial, development of new metastatic lesions was evaluated using serial computed tomography scans. Results: In vitro, ganetespib blocked the migration of cancer cells and reduced the expression of key drivers of metastasis including P-AKT, FAK, HER2, IGF-1R, MET, HIF-1α, and VEGF. In vivo, ganetespib significantly reduced tumor angiogenesis and proliferation. In patients, in the population in the GALAXY–1 trial that exhibited the strongest survival improvement (diagnosis of advanced disease >6 months, N=175), radiologic progressions due to new lesion formation were 19 (50%) vs. 5 (17%), for D vs. D+G, respectively, at time of abstract submission. Updated results will be presented. Conclusions: Ganetespib inhibits multiple processes involved in tumor metastasis. Preliminary data from the GALAXY–1 study support reduced frequency of progression due to new metastatic lesion formation in advanced NSCLC patients treated with ganetespib.
Retrospective analysis of the clinicopathologic profile of ALK-positive patients in the south of Spain.
Authors: Gonzalez de la Peña Miriam , Biscuola Michele , Sanchez Gastaldo Amparo , Alonso Miriam , Gomez Izquierdo Lourdes , Corral Jesus 
Published: March 2020

e19105 Background: The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non small cell lung cancer (NSCLC). ALK rearragement is detected in 2-7% of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method of detection. The clinical features of lung cancer that harbors ALK include light- or never-smokers, younger age, adenocarcinomas with acinar pattern or signet ring adenocarcinoma, and a lack of EGFR or KRASmutations. Crizotinib has shown an important benefit in terms of overall response rate (ORR) and progression free survival (PFS) in the 2nd/3rd line setting. Treatment related adverse events include gastrointestinal and visual disorders. Methods: Retrospective analysis of the clinico-pathological profile of ALK NSCLC patients between May 2011 and December 2012 in our region. Results: 10 cases (6,7%) were identified from 150 screened patients with adenocarcinoma histology and EGFR wild-type status. 7 (70%) patients were women. Median age at diagnosis was 62 years old (36-77). 9 (90%) patients were light-or-never smokers. All tumors were adenocarcinomas with EGFR wild-type status: Acinar growth pattern was detected in 4 cases (40%); 4 (40%) patients showed mucous cells and previous described signet-ring cells were detected in the last 2 (20%) cases. Only 5 (50%) patients received crizotinib therapy: 2 patients were treated during 1st line with partial response, 1 patient on 2nd line with stable disease and 2 patients received treatment in 3rdline with partial response. Only one patient required a dose reduction due to a grade 3 nausea and mucositis. Conclusions: Most of the patients with ALK rearragements in our serie have clinical and pathological characteristics to previously described. More women and older population were showed. In stead of the small sample size, pathological pattern based on acinar growth and mucous or signet-ring cells in adenocarcinomas with no EGFR mutation should guide the ALK screening. ORR and toxicity profile confirmed Crizotinib benefit as soon as ALK status was detected.
Erlotinib (E) in non small cell lung cancer (NSCLC) patients (pts) ≥75 years old with comorbidities (cM): Experience at a tertiary referral center.
Authors: Syrigos Konstantinos N. , Sarris Evangelos , Strimpakos Alexios S 
Published: March 2020

e19111 Background: Besides chemotherapy, E is another option in NSCLC pts especially in those with EGFR mutations. Elderly pts enrolled in trials are fit without cM, but in clinical practice most suffer from cM. Methods: Medical records of 1221 pts diagnosed with NSCLC between 2008-2012 were screened. We examined pts ≥75 yrs for demographics, clinical data and Tx details. Results: 233/1221 NSCLC pts received E at any line. 53/233 (23%) were ≥75 yrs old. Male:female ratio was 34:19 and median age 79 yrs (range 75-88). NSCLC subtypes included 31 adenoca, 8 squamous cell, 9 NOS and 5 others. 50/53 pts had cM (≥2 in 46 pts, 1 in 4pt). Main cM were cardiovascular disease (n=41), COPD (n=14), other cancer (n=10) and diabetes (n=8). 8 pts were tested for EGFR mutations (5 -ve, 3 +ve). Performance Status was satisfactory (ECOG 0-1) in 8 pts and poor (2-3) in 45pts. 8pts were treated with E 100mg and 45 pts with E 150mg (12 pts needed dose reduction). Complete follow up data were found in 46pts. Mean duration of treatment was 79 days (range 9-662). 35/46 pts experienced side effects (s.e) [rash n=29, diarrhea n=17] which led to treatment discontinuation in 12pts. Pts with abnormal creatinine clearance (n=13) were more likely to stop treatment due to s.e (6/13 versus 6/33). 17/46 pts (37%) achieved disease control (5 PR, 12 SD) and a time to progression (TTP) of 157 days (range 106-662, 95% CI 132.79-270,74) while 22/46 pts had PD as best response (TTP 49d, range 19-88, CI 44,67-64,97). 7pts were not evaluable (stopped Tx due to s.e). All EGFR+ve pts had disease control (2PR, 1SD). Conclusions: E is a valuable option in elderly NSCLC patients with co-morbidities, especially if they harbor EGFR mutations. Impaired renal function might be associated with propensity to side effects and early Tx discontinuation.
Volumetric tumor growth in advanced NSCLC patients (pts) with EGFR mutations during EGFR-TKI therapy: Developing criteria to define slow progression.
Authors: Nishino Mizuki , Dahlberg Suzanne Eleanor , Cardarella Stephanie , Jackman David Michael , Rabin Michael S. , Ramaiya Nikhil H. , Hatabu Hiroto , Janne Pasi Antero , Johnson Bruce E. 
Published: March 2020

e19125 Background: EGFR-mutated advanced NSCLC pts treated with EGFR TKI typically progress after an initial tumor response. Most pts continue TKI beyond RECIST progression, and an objective guide for treatment decisions is needed. We analyzed the volumetric tumor growth in these pts as an initial step to develop criteria for slow progression to aid therapeutic decision making. Methods: The study population included 58 advanced NSCLC pts with sensitizing EGFR mutations, treated with first-line single-agent gefitinib or erlotinib between 2002-2011, who had baseline CT showing measurable lung lesion and at least two follow-up CTs while on TKI and experienced volumetric tumor growth. Tumor volume (mm3) of the dominant lung lesion was measured on baseline and all follow-up chest CT scans during therapy, using volume analysis software [Nishino et al. Acad Radiol. 2011]. A total of 405 volume measurements from nadir to the end of TKI therapy or last follow-up, with data closure on 6/1/12, were analyzed in a linear mixed effects model, fitting time as a random effect [Laird and Ware, Biometrics, 1982]. Results: Among 58 pts, 46 (79%) were female, median age was 62 (range: 35-84), 29 (50%) were never-smokers, 53 (91%) were stage IV at diagnosis, and 53 (91%) received erlotinib. The median time on TKI was 15.8 months. The median time to tumor nadir was 6.3 months. A linear mixed effects model was fitted to predict growth of the logarithm of tumor volume (logeV), adjusting for time in months from baseline. The growth rate of logeV, obtained as the regression coefficient for time, was 0.12/month (SE: 0.015; p<0.001; logeV=0.12*months+7.68). The model provided a reference value for the volumetric tumor growth rate in EGFR-mutant NSCLC pts after they have achieved their nadir. Conclusions: Tumor volume analysis defined volumetric tumor growth after the nadir in EGFR-mutant advanced NSCLC pts receiving TKI. This provides a reference value for the tumor growth rate in pts progressing after the nadir on TKI. Based on these data which can be studied in additional cohorts, we are currently developing practical radiographic criteria to help define patients as slow progressors who can safely remain on EGFR TKIs.
A phase II trial of a cremophor-free, polymeric micelle formulation of paclitaxel and gemcitabine in patients with advanced non-small cell lung cancer.
Authors: Ahn Hee Kyung , Hong Junsik , Kang Shin Myung , Sym Sun Jin , Park Jinny , Shin Dong Bok , Lee Jae Hoon , Cho Eun Kyung 
Published: March 2020

e19129 Background: Non-platinum doublet paclitaxel and gemcitabine has shown efficacy on par with platinum-based doublet regimens as first-line chemotherapy in advanced non-small cell lung cancer patients. Genexol-PM is a Cremorphor EL(CrEL)-free polymeric micelle formulation of paclitaxel. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients. Methods: This is a single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230mg/m2 on day 1 and gemcitabine 1000mg/m2 on day 1 and day 8 of a 3-week cycle as first-line chemotherapy. Six cycles of chemotherapy were administered unless there is a disease progression. The primary endpoint was response rate. Results: Forty-three patients received the study drugs with median of 4 cycles per patient (range, 1-6). Among 35 patients who received more than one cycle, mean dose intensity of CrEL-free paclitaxel and gemcitabine was 209 mg/m2/3-week and 1,853 mg/m2/3-week respectively. Overall response rate was 46.5%. The median progression free survival was 4.0 months (95% CI 2.0-6.0 months) and median overall survival was 14.8 months (95% CI 9.1-20.5 months). 18 patients (51%) experienced grade 3/4 adverse events, including neutropenia or febrile neutropenia (n=7), pneumonia (n=3), asthenia (n=3), peripheral neuropathy (n=2), diarrhea (n=1), skin rash (n=1), myalgia (n=1), pulmonary thromboembolism (n=1), LV dysfunction (n=1), and dyspnea with sudden death (n=1). Adverse events leading to drug discontinuation were occurred in 9 patients, among which 2 patients were died of adverse events (pneumonia, dyspnea with sudden death). Conclusions: CrEL-free paclitaxel in combination with gemcitabine demonstrated comparable antitumor activity with less emetogenicities in non-small cell lung cancer patients. Clinical trial information: NCT01770795.
Phase II study of danusertib (D) in advanced/metastatic non-small cell lung cancers (NSCLC).
Authors: Gauler Thomas Christoph , Besse Benjamin , Novello Silvia , Smit Egbert F. , Plummer Elizabeth R. , Delord Jean-Pierre , Nicodemo Maurizio , Santoro Armando , Barone Carlo , Marchetti Paolo , Conte Pier Franco , De Jonge Maja J. , Awada Ahmad , Mariani Mariangela , Jannuzzo Maria Gabriella , Petroccione Anna , Ceruti Roberta , Davite Cristina , Eberhardt Wilfried Ernst Erich 
Published: March 2020

e19138 Background: D is an ATP competitive pan-aurora kinases inhibitor with activity also against FGFRs, VEGFR, Ret, TrkA, Scr, and Abl. Methods: Eligible pts had NSCLC progressing for advanced/metastatic disease after 1 prior chemotherapy line (CT). Primary endpoint was progression-free survival at 4 months (PFS-4) evaluated in a Simon two-stage design. Number of successes required for not rejecting the alternative hypothesis (40% PFS-4) was ≥4/19 evaluable pts while the number of successes required to reject at the end of stage 2 the null hypothesis (20% PFS-4) was ≥11/36 (α 1-sided = 0.1). D was administered at 500 mg/m² as 24 hr IV infusion q2w. The expression of Aurora A/B, TPX-2, MDR, Scr, Survivin by IHC and the amplification of FGFR1 by FISH on tumor biopsies of consenting pts were evaluated. Results: 3 out of 19 evaluable pts were PFS-4 at the end of the 1st stage, thus precluding passage to the 2nd stage. Interestingly, in pts with squamous (SCC) (n=7), median PFS and OS were 6.4 and 10.6 mos respectively (vs. 2.2 and 7.6 mos, in non-SCC pts), suggesting a possible specific effect in this subtype. Additional pts with SCC were therefore treated under a protocol amendment. At the end of this 2nd stage, 5/31 evaluable SCC pts (80% CI: 0.08-0.28) were PFS-4 indicating that the predefined threshold required to conclude for activity would not have been reached. Overall 56 pts, all histology NSCLC, were treated: median age 62 yrs (39-79), 64% male, 70% SCC, 36% with >1 prior CT. Best response was a PR in 1 pt and SD in 20 pts; median PFS and OS were 2.1 and 8.3 mos respectively. The most frequent drug-related AEs (any Grade, ≥20%) were: uncomplicated and short lasting neutropenia (94%), nausea (39%), fatigue (37%), asthenia (30%), anorexia and diarrhea (29%), alopecia (23%). Histological analyses by IHC and FISH is still ongoing: results will be presented. Conclusions: Limited evidence of activity was observed, insufficient to meet the predefined threshold to call efficacy in NSCLC when D was administered as monotherapy at this dose/schedule. D confirmed to have a manageable safety profile. Clinical trial information: 2006-003772-35.
Time trends in overall survival (OS) gain in advanced non-small-cell lung cancer (NSCLC).
Authors: Saad Everardo D. , Buyse Marc E. , Jassem Jacek 
Published: March 2020

e19144 Background: There is an ongoing debate about the adequacy of OS as primary endpoint (PEP) in phase III trials in various tumor types, including NSCLC (Soria Ann Oncol 2010). Moreover, median OS and post-progression survival are increasing in NSCLC (Hotta PLoS One 2011 and Hayashi Ann Oncol 2012). We assessed the frequency and time trends in OS gain in recent trials. Methods: We searched PubMed for phase III trials in advanced NSCLC published between January 1998 and December 2011 in 13 leading journals. The PEP was the endpoint stated explicitly, used for N calculation, or listed first. Gain in OS was ascertained when there were significant differences in any pairwise comparison on OS following the original authors’ definitions. Results: We retrieved 148 trials that enrolled a total of 70,716 patients in 325 trial arms. The median number of patients per arm was larger for the 2005-2011 period than for the 1998-2004 period (207 vs 150; P<0.01). OS was used as PEP alone in 99 trials, and as one of the co-primary endpoints in 3 trials (the PEP could not be ascertained for one trial). There was no trend regarding the use of OS as PEP in the two periods compared, either overall (P=0.44) or in first line (P=0.41). Gain in OS according to trial features is shown in the Table. Conclusions: Significant gains in OS appear to decrease along the years, despite the growth in size of NSCLC trials and the continued use of OS as PEP. [Table: see text]
Phase I/II trial of combination nab-paclitaxel and pemetrexed in advanced solid tumor patients (pts) with emphasis on non-small cell lung cancer (NSCLC).
Authors: Riess Jonathan , Ho Cheryl , Davies Angela M. , Lau Derick , Lara Primo , Chew Helen K. , Beckett Laurel , Sangha Randeep S. , Mack Philip C. , Gandara David R. 
Published: March 2020

e19147 Background: Despite advances in targeted therapies, there is an ongoing need to develop new and effective cytotoxic drug combinations in NSCLC. Preclinical evaluation has demonstrated additive cytotoxicity of pemetrexed and taxanes. We evaluated the safety and efficacy of combining nab-paclitaxel (nP) and pemetrexed (P) in solid tumors with a focus on NSCLC for the phase II expansion. Methods: A 3+3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels were tested: P 500 mg/m2 day 1 plus nP on day 1 at doses of 180, 220, and 260 mg/m2 every 21 days. Dose limiting toxicity (DLT) in cycle 1 was defined as: grade 4 platelets or grade 3 platelets with bleeding, neutropenia with fever or documented infection, or other grade ≥ 3 non-heme toxicity. Phase II eligibility included advanced NSCLC, ≤ 2 line prior therapy, PS 0-1, adequate organ function. Primary endpoint for further study was response rate (RR) ≥ 25%. Results: Planned dose escalation during the Phase I portion was completed without reaching the MTD. The RP2D was P 500 mg/m2 and nP 260 mg/m2. The phase II portion accrued 37 pts before early closure due to increasing use of first-line pemetrexed/platinum doublet therapy in non-squamous NSCLC. Phase II patient characteristics: median 63 (45-77); M:F 23:14; median cycles 3. In 31 assessable patients: 5 PR, 12 SD and 14 PD. Efficacy: RR =14%; disease control rate (DCR) = 46%; median survival time (MST) = 8.7 months. Pts in the DCR group had a MST of 15.4 vs 4 months in the PD group (p=0.02). Conclusions: P 500 mg/m2 day 1 with nP 260 mg/m2 was feasible and well tolerated. The phase II component demonstrated activity in second-line therapy of advanced NSCLC. Practice patterns have evolved; so further trials of this regimen are not planned. Clinical trial information: NCT00470548.