bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erlotinib in the “real life”: Retrospective results in NSCLC in two Italian centers.
Authors: Lorusso Vito , Saracino Valeria , Romano Giampiero , Nacci Angelo , Leo Silvana Assunta , Chiuri Vincenzo Emanuele , Pellegrino Antonio , Rizzo Pietro , Giampaglia Marianna , Cinefra Margherita , Cinieri Saverio 
Published: March 2020

e18048 Background: Erlotinib is an oral tyrosine kinase inhibitor, approved for treatment of advanced NSCLC after the failure of more than 1 or 2 previous chemotherapy regimens. Its efficacy is comparable to that of chemotherapy, however, some concerns have been raised on its activity in pts with poor PS or in those not harboring EGFR mutation. Methods: Wereviewed the medical records of pts treated with erlotinib in the last 5 years in two Oncologic Centers of South Italy, with the aim to correlate response to pts characteristics. Results: Since January 2006 we have treated with erlotinib 388 pts affected by stage IIIb-IV NSCLC as 2nd, 3rd or 4th line of therapy. Median age was 67 (range 23-90), 300 were males and 88 women. Histology was ADK in 214 (55.2 %), SQM in 129 (33.2%) BAL in 12 (3.1%) and other in 33 (8.5%). Stage IIIb/IV was 66/322 (17%/83%). PS was 0 in 90 (23.5%), 1 in 214 (57.4%), 2 in 60 (15.5%) and 3 in 14 (3.6%) pts, respectively. Smoking status was: never smoker 60 (15.6%), ex smoker 276 (71%), currently smoker 52 (13.4%). With regard to the line of therapy, 250 pts (64%) were treated as 2nd line, 113 (29.1%) as 3rd line and 25 (6.5%) as 4th line. Overall, 117 pts (30%) received only the first drug supply and were lost to follow-up, 131 (33.4%) received 2 or 3 drug supplies, 134 (35.7%%) 4-30 drug supplies and 5 pts (0.9%) > 30 drug supplies, respectively. According to RECIST Criteria, 20/256 evaluable pts (11 too early, 121 not evaluable) achieved PR (7.8%), 74 SD (28.9%) and 162 (63.2%) progressed. The characteristics of the responding pts were as follows: 12 women and 8 men, 15 ADK, 4 SQM and 1 other histology (undifferentiated), 9 never smoker, 10 ex smoker and 1 current smoker, PS 0/1/2 in 8/9/3 pts; line of therapy 2nd/3rd/4th in 16/4/0. The median duration of response was 10 months (range 3 to >30). Median duration of SD was 9 months. Responding pts had a median survival of 28 months (range 3-105). Conclusions: These retrospective data suggest a more cautious usage of the drug, in order to avoid the huge number of pts lost to follow-up. In fact, erlotinib should not be prescribed in pts with poor PS and in lines beyond the 3rd, unless for pts harboring EGFR mutation.
Clinical benefits of sequential administration of docetaxel and intermittent erlotinib as a second-line therapy for advanced non-small cell lung cancer (NSCLC): A phase II randomized study.
Authors: Aparisi Francisco , Sanchez-Hernandez Alfredo , Giner Vicente , Muñoz-Langa José , Esquerdo Gaspar , López Jiménez Antonio , Garde Javier , Garcia Sanchez Jose , Juan Vidal Oscar 
Published: March 2020

e18049 Background: Patients (p) with advanced NSCLC have few treatment options after progressing to 1st-line platinum doublet chemotherapy. Several preclinical and phase I studies have suggested that sequential administration of erlotinib (E) and docetaxel could avoid possible negative interactions and optimize the benefit obtained against NSCLC. This randomized phase II was designed to address the clinical benefit obtained with the use of sequential administration of docetaxel and intermittent E. Methods: 70 p with advanced NSCLC progressing to previous PDC for advanced disease were randomized (1:1): Group A (n = 34): Docetaxel 75 mg/m2 day 1 and intermittent E (day 2-16), up to 4 cycles, followed by E in monotherapy; and Group B (n = 36): E in monotherapy. Treatment was administered until unacceptable toxicity or disease progression. Primary endpoint: rate of p free of progression at 6 months; secondary endpoints: progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. The study has completed enrolment. At the date of cut-off for this communication, data of 60 patients were available: 30 in Group A/30 in Group B. Results: Baseline characteristics: non-adenocarcinoma (60.3%), current/former smokers (95%), male (90%) and stage IV (87.9%). 6 months PFS: 13.5% in the sequential arm. PFS: 2.7 months (m) in Group A (95% CI 2.1 – 3.8) and 2 m in Group B (95% CI 1.7 – 2.4) p value 0.08. Median OS: 11.0 m (95% CI 4.5 – 13.4) in group A and 4.7m (95% CI 2.5 – 6.6) in Group B with a p value 0.02. DCR: 44.4% in the experimental group whereas in the E one was 30.8%. Adverse events (AEs), including skin rash and diarrhea, were all generally tolerable. Of interest, the low number of p developing neutropenia in the D + E arm. Conclusions: Although the primary objective has not been met, an encouraging benefit on survival has been shown in the exploratory analysis, with a median overall survival of 11 months for patients treated with the sequential regimen (p value 0.02). Final data will be presented during the meeting.
Quantification of circulating endothelilial cells (CECs) as a predictor of response to chemotherapy with platinum and pemetrexed in patients with nonsquamous non-small cell lung carcinoma.
Authors: Sanchez-Hernandez Alfredo , Garcia Sanchez Jose , Blanco Remei , Maciá Sonia , Esquerdo Gaspar , Aparisi Francisco , Garde Javier , Catot Silvia , Vidal Jose , Garcia-Pinon Francisco , Juan Oscar 
Published: March 2020

e18053 Background: CECs play an important role in tumor neovascularisation and may have prognostic value in cancer patients (pts). The objective of this study is to assess the quantification of CECs as a predictor of response to chemotherapy (CT) in non-squamous NSCLC. Methods: 10ml of blood was obtained prior to the first, second and third cycle of CT in pts treated with platinum plus Pemetrexed. The quantification of CECs was undertaken using CellSearch technology in a central laboratory. The basal levels and the evolution of CECs was correlated with response to treatment according to RECIST criteria after 3 cycles of CT using analysis of variance (ANOVA). Results: Between July 2010 and June 2011 67 pts were included: 43 pts (64.2%) received CDDP/PEM and 24 (35.8%) received CBDCA/PEM. Median age: 60 years (range 40-82), 46 male (68,7%). Nine (13,4%) PS 0; 46 (68,7%) PS 1; 11 (16,4%) PS 2; 1 (1,5%) PS 3. Range of basal CECs: 8 - 1171 cel (median of 85 cel). CECs prior to cycle 2: median of 100 cel (range: 10-1388). CECs prior to ciclo 3: median of 94,5 cel (range: 5-1857). Response after 3 cycles was: 25 PR (36%), 17 SD (25%) and 16 PD (23%) and 11 NE (16%). In the analysis of variance, no significant relationship between the basal CEC count and response was found (p-value=0,831). Decrease >50% between the 1st and 2nd cycle is correlated significantly with progression disease (p=0.026). Conclusions: In this homogeneous group of patients with NSCLC there is no correlation between response to treatment and basal levels of CECs. The decrease in CEC numbers after the first cycle could be a negative predictive factor. The correlation between the variations of CECs with PFS and OS will be presented during the conference.
Oral S-1 and carboplatin plus bevacizumab with maintenance S-1 and bevacizumab for chemo-naive patients (Pts) with advanced non-squamous non-small cell lung cancer (NSCLC).
Authors: Kaneda Hiroyasu , Urata Yoshiko , Okamoto Isamu , Hattori Yoshihiro , Okuno Keiko , Shimada Temiko , Takeda Masayuki , Kurata Takayasu , Miyazaki Masaki , Terashima Masaaki , Tanaka Kaoru , Kiyota Hidemi , Hayashi Hidetoshi , Kudo Toshihiro , Okabe Takafumi , Azuma Koichi , Morita Satoshi , Nakagawa Kazuhiko , Negoro Shunichi , Satouchi Miyako 
Published: March 2020

e18060 Background: Our previous phase III trial has demonstrated that S-1 in combination with carboplatin has promising activity as well as superior toxicity profile compared with carboplatin/paclitaxel for the first-line treatment of advanced NSCLC (JCO vol28, 2010). This study evaluated the efficacy and safety of new combination of S-1 and carboplatin plus bevasizumab (Cb/S1/Bev) followed by continuation maintenance of S-1 and bevacizumab (S1/Bev) in chemo-naïve Pts with advanced non-squamous NSCLC. Methods: Pts receive carboplatin AUC 5 and bevacizumab 15 mg/kg on day 1 plus oral S-1 (40 mg/m2 b.i.d. ) on days 1 to 14. Treatment is repeated every 21 days up to 6 cycles. For the patients with SD or PR, S-1 combined with bevacizumab are continued every 21 days until disease progression or toxicity. Primary endpoint of this study was overall response rate (ORR). Results: Between April 2010 to October 2011, 48 patients were enrolled. Median age was 65 years (range=F35-77), male/female=33/15, PS 0/1=15/33, adeno/non-adeno=42/6. Median cycles of Cb/S1/Bev treatment were 4 (range=1-6), and 59% (n= 28) of Pts shifted to maintenance therapy. Among Pts who shifted to maintenance phase, median cycles treated with S1/Bev were 3.5 (range=1-10). Grade 3/4 toxicities included: neutropenia (23.4%/4.3%), anemia (4.3%/6.4%), thrombocytopenia (6.4%/6.4%) and hypertension (8.3%/0%). No treatment related death was occurred. Forty-six pts were evaluable for response. ORR was 50 % and disease control rate was 78 %, with a median time to progression of 7.4 months (95% CI: 3.9-10.8). Conclusions: Treatment with S-1 and carboplatin plus bevacizumab with maintenance S-1 and bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this new regimen.
Utility of a novel quantitative EGFR-mutated protein analysis using AQUA system for EGFR-TKI treatment in non-small cell lung cancer.
Authors: Goto Koichi , Ishii Genichiro , Fujimoto-Ouchi Kaori , Shirane Masatoshi , Saito Tatsuro , Nishiwaki Morie , Ohmatsu Hironobu , Niho Seiji , Yoh Kiyotaka , Umemura Shigeki , Yamane Yuki , Shiozawa Toshihiro , Yamaguchi Yoko , Taira Tetsuhiko , Nagai Kanji , Ohe Yuichiro 
Published: March 2020

e18064 Background: Lung cancer carrying EGFR mutation (muEGFR) expresses good response to EGFR tyrosine kinase inhibitors (TKIs). However, not all patients (pts) with mutation showed similar clinical benefits from EGFR-TKIs. Heterogeneity of tumor cells is considered to be one plausible reason. MuEGFR was usually genotyped in qualitative manner in present clinical practice. In addition, new technology of AQUA system enables us to measure protein levels objectively with considering expression heterogeneity in tissues. Here we investigated the correlation between AQUA score obtained from each specimen and the response and the response duration by EGFR-TKIs. Methods: Slice sections from genotyped 105 pts with muEGFR and 33 pts with wild-type EGFR were stained by E746-A750 deletion (6B6)- and L858R (43B2)-specific antibodies. Homo- or heterogeneous staining and muEGFR protein levels of these specimens were evaluated with AQUA system. Results: Concordance rate between genotypes and AQUA-based phenotypes (deletion and L858R), with cut-off values based on ROC curve, were 60% and 82%. Low sensitivity of 6B6 was due to lucking of reactivity for other deletion variants. Alternatively, specificities of both antibodies were 96% and 92%, indicating highly selectivity to muEGFR protein. The AQUA score of 27 pts treated with EGFR-TKIs were varied (8.7 – 907.4) but the falls plot analysis indicated that pts with high AQUA score showed better objective response. Specimens of partial response (PR) had significantly higher AQUA score than those of progression disease (136.5 vs 9.8, p=0.014). When divided pts into two groups based on median AQUA score, the pts with high AQUA score showed a tendency of longer treatment duration (21 mo vs 14 mo, p=0.162). These results indicate that AQUA-based analysis can classify pts carrying genotyped muEGFR into susceptible and less susceptible ones to EGFR-TKIs. Conclusions: We observed that pts with high AQUA score were more sensitive to EGFR-TKIs. It is important for predicting sensitivity to EGFR-TKIs to investigate not only genotyping but also muEGFR protein levels by using AQUA system.
The predictive value of clinical variables in patients affected with non-small-cell lung cancer (NSCLC) treated with pemetrexed (PEM) plus platinum-based regimen: A retrospective analysis.
Authors: Fabbri Maria Agnese , Moscetti Luca , Nelli Fabrizio , Gamucci Teresa , Mansueto Giovanni , Narducci Filomena , Quadrini Silvia , Sperduti Isabella , Passaro Antonio , Campenni Giuseppe , Cortesi Enrico , Martelli Olga , Bianchetti Sara , Angelini Francesco , Pellegrino Arianna , Pavese Ida , Signorelli Carlo , Ruggeri Enzo Maria 
Published: March 2020

e18065 Background: PEM plus platinum–based regimen is a standard of care in chemonaïve advanced non-squamous NSCLC pts. This retrospective multicenter analysis was performed to evaluate the predictive value of clinical variables for PFS in an unselected population. Methods: Data were obtained by reviewing the clinical data of pts affected with advanced NSCLC treated from 2009 to 2011. 193 pts were retrieved. Main characteristics were: median age: 63 years (range 33-79); male/female (M/F): 67%/33%; ECOG PS 0-1: 97%; weight loss >5%: 34%; current smoker 31%. Stage IV disease: 81% ; ≥ 1 site of metastasis: 79%. Brain metastasis: 28% of pts at diagnosis. Results: All 193 pts are evaluable for analysis. 158 pts (82%) received the cisplatin- and 35 pts (18%) the carboplatin-based regimen. Most pts received at least 2 cycles of therapy and 21% received PEM maintenance treatment. The overall disease control rate observed was 69%. (CR+PR = 44%, SD 25%). At a median follow-up of 6.7 months (range 1-22), the median PFS was 6 months (95%CI 5-7) with a 1 year-PFS rate of 16.8%. In the Cox multivariate analysis, factors found to be associated with a statistically significant longer PFS were: gender (M vs F, HR 1.68, C.I.95% 1.19-2.38; p=0.003); no. of metastatic site (>1 vs 1, HR 1.6, 95%CI 1.07-2.40; p=0.02); type of response (CR/PR vs no response, HR 2.74, 95%CI 1.95-3.86; p<0.0001); and maintenance treatment (no vs yes, HR 2.74, 95%CI 1.95-3.86; p=0.02). The Kaplan-Meyer analysis of 1-year PFS confirmed female gender (F vs M 24.4% vs 12.2%, log-rank p=0.01), objective response (CR/PR vs SD/PD 29.9% vs 5.2%, log-rank p<0.0001), and maintenance therapy (yes vs no 30% vs 17.3%, log-rank p=0.01) as the significant clinical variables predictive of longer survival. Conclusions: According to our data only female gender, responsive disease and subsequent maintenance therapy were independent predictive factors. No difference in term of PFS outcome were found for elderly pts, presence of brain metastases and weight loss at diagnosis. Overall survival data will be presented.
Whole-brain radiotherapy in NSCLC patients with brain metastasis: Who benefits and by how much?
Authors: Jain Pooja , Montazeri Amir H , Alam Farida , Eswarvee Chinnamani , Husband David J. , Ibrahim Azman , Malik Zafar I , Schofield Penny , Shenoy Aditya , Sivapalasuntharam Asha , Whitmarsh Karen A , Wong Helen , Littler John 
Published: March 2020

e18068 Background: NSCLC patients with brain metastasis have poor survival even with whole brain radiation therapy (WBRT) alone or in combination with surgery (S+WBRT). The aim of the audit was to identify any prognostic factors which can aid treatment decisions. Methods: A retrospective study of patients with brain metastasis from NSCLC, diagnosed between July 2008 and December 2010 was carried out. Patient characteristics, RPA score at the time of presentation, treatment modality, radiotherapy dose fractionation, time to progression, date of death and primary or secondary presentation were collected. The data was analysed using descriptive statistics; overall survival was calculated using the Kaplan-Meier estimates and compared with the Log-rank test. Multivariate analysis was carried using the Proportional Hazards Model. Results: Of the 156 patients included, 52% presented as primary manifestation and 48% as secondary. The mean age of the audit population was 64.4 year, with 60% of patients falling in the RPA II category. Histology was not available in 27 (18%) of the patients. Majority (79%) were treated with WBRT alone, 3 patients had stereotactic radiosurgery in combination with WBRT and 19% had S+WBRT. 9 (6%) patients did not complete WBRT. Median follow up is 3.8 months (0.5-34.5). Overall survival (OS) for the whole group is 4 months. Better survival was seen with S + WBRT (8 vs. 4 months, p <0.01) and primary presentation (5 vs. 4 months, p=0.009). RPA classification significantly influenced survival in the S + WBRT arm (12 months vs. 7 months for RPA I, p=0.009). On multivariate analysis of the various prognostic factors in the WBRT group, RPA classification and higher RT dose (30 Gy/10#) were associated with better survival (OR 2.3 95%CI 1.6-3.4). Patients treated with SRS have the best survival (11 months). Conclusions: RPA classification is the strongest predictor for outcome following treatment for brain metastasis. These findings can assist in better patient selection and optimising radiotherapy dose fractionation to improve survival outcome. It will be interesting to see if QUARTZ trial supports these findings and clarify the benefit of WBRT in patients with NSCLC.
A phase I trial of gefitinib and nimotuzumab in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Kim Han Sang , Cho Byoung Chul 
Published: March 2020

e18080 Background: Nimotuzumab (TheraCIM) is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with minimal skin toxicity. Combining a different class of anti-EGFR drug with gefitinib is a new strategy to overcome intrinsic and acquired resistance to gefitinib. The aim of this phase I trial was to determine recommended phase II dose (RPIID) and the safety of gefitinib and nimotuzumab combination treatment. Methods: Patients with advanced/metastatic NSCLC were treated with escalating doses of weekly nimotuzumab (100 mg or 200 mg, IV) and fixed doses of daily gefitinib (250 mg/day, PO) until disease progression or unacceptable toxicity. We designed to enroll additional 10 patients at RPIID for the safety analysis. EGFR mutations and KRAS mutations were analyzed from available tumor samples. Results: A total of 16 patients were enrolled (3 in 100 mg cohort, 13 in 200 mg cohort). Six patients (40%) were female, and 5 (33.3%) were never smokers. Adenocarcinoma was the major histologic type (13 patients, 81.3%).Treatment was well-tolerated without dose-limiting toxicity (DLT). Three patients (18.7%) experienced grade 2 skin toxicity (1 in 100 mg cohorts, 2 in 200 mg cohort). Other common grade 1/2 toxicities were fatigue (37.5%) and diarrhea (25.0%). Among 16 evaluable patients, four patients (28.6%) achieved partial response and 5patients (35.7%) had stable disease. Two of 4 responders had EGFR mutation (exon 19 deletion). Conclusions: Dual agent molecular targeting of EGFR with nimotuzumab and gefitinib in patients with advanced NSCLC is well-tolerated. The RPIID for nimotuzumab is 200mg weekly IV and for gefitinib 250 mg/day PO. Based upon this phase I trial, we are planning to conduct a randomized phase II trial comparing gefitinib and nimotuzumab with gefitinib alone in patients with advanced NSCLC.
Neutrophil to lymphocyte ratio as a prognostic indicator for advanced non-small cell lung cancer patients: A retrospective study.
Authors: Yao Yanwen , Yuan Dongmei , Liu Hongbing , Gu Xiaoling , Song Yong 
Published: March 2020

e18082 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to be a prognostic indicator for different types of cancer. We aimed to investigate the prognostic significance of NLR in advanced non-small cell lung cancer (NSCLC) patients. Methods: From January 2007 to December 2010, total 201 patients who were histologically diagnosed NSCLC, staged for the TNM stage III or IV and chemotherapy-naïve were included. All patients were followed up until August 1st 2011. NLR was calculated from lymphocyte and neutrophil count on routine blood tests taken before diagnosis or first-line therapy. Results: The median survival time of all included patients was 354 days and mean value of NLR was 4.06. Cases were distributed into two groups at NLR value of 4.06. Multivariate analysis demonstrated that NLR was an independent and significant prognostic factor in overall survival (OS) (Hazard Ratio, HR=1.659, 95% Confidence Interval, CI=1.075-2.559, p=0.022). Conclusions: The results suggested that the elevated NLR predicted poor OS for advanced NSCLC patients. It may be a potential biomarker to stratify higher risk of death in advanced NSCLC patients, and this kind of patients may be supposed to more aggressive treatment to pursuit longer survival.
Prospective correlative study of FDG-PET SUV and proteomic profile (VeriStrat) of non-small cell lung cancer patients treated with erlotinib.
Authors: Lazzari Chiara , Tiseo Marcello , Gregorc Vanesa , Latteri Fiorenza , Ippolito Massimo , Balderi Segio , Cosentino Sebastiano , Scarlattei Maura , Roder Heinrich , Grigorieva Julia , Roder Joanna , Bordonaro Roberto , Ardizzoni Andrea , Gianni Luca , Soto Parra Hector J. 
Published: March 2020

e18096 Background: Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI TOF MS) was used to create and validate a plasma proteomic algorithm VeriStrat (VS), based on 8 m/z peaks, and able to select advanced NSCLC pts who may benefit from EGFR TKIs. The algorithm was associated with PFS and OS of patients treated with EGFR TKIs and not with chemotherapy. Standardized Uptake Value (SUV) is of prognostic value for survival in non-small cell lung cancer. Aim of the current study was to analyze the OS and TTP in advanced NSCLC pts treated with erlotinib (E) according to baseline VeriStrat classification and baseline SUVs of FDG-PET. Methods: Plasma samples were collected before the beginning of E from metastatic NSCLC patients. Acquired spectra were classified according to the VeriStrat algorithm. The FDG-PET was performed the day before the beginning of E. Results: Thirty eight NSCLC pts on E therapy with the following characteristics were analyzed: median age 62 years old, 63% were males, 53% had adenocarcinoma histology, response rate was 26%, median OS 10 mos and (TTP) 3.4 mos. Twenty-six (68%) were classified as VS Good, 12 (32%) as Poor. TTP and OS for VS Good and Poor were 4.1 vs 2.1 mos (HR 0.86, log-rank p=0.6) and 11.1 vs 4.1 mos (HR 0.45,log-rank p=0.02), respectively. Baseline SUV levels were associated with TTP (Wilcoxon test p=0.001) but not with OS (all pts progressed, 5 still alive). All Poor classified pts had SUV ≥ 7 and had the worst TTP and OS; VS Good classified patients had worse TTP and OS if their baseline SUV level was > 7 than those who were VS Good and had SUV<7(see Table: 3-curves comparison log-rank test p value for a trend). Conclusions: We confirmed that pts with VS Poor classification have significantly shorter OS than those classified as VS Good. Pts with VS Good profile and with low baseline SUV levels may benefit more from EGFR TKI than VS Good pts with high SUV.