bluuebunny/crossref_metadata_2025_split huggingface dataset:
Older patient participation in SWOG lung cancer trials: Comparative analysis from 1993 to 2008.
Authors: Hesketh Paul Joseph , Redman Mary Weber , Unger Joseph M , Moon James , Gandara David R. 
Published: March 2020

7570 Background: In 1999, SWOG published a study demonstrating the underrepresentation of patients 65 years and older on clinical trials (Hutchins NEJM). A second report published in 2006 demonstrated increasing proportions of patients > 65 years (31% 1997-2000; 38% 2001-2003) being enrolled into SWOG trials (Unger JCO). Older patient enrollment was still disproportionately low compared to the US cancer population. The current analysis focuses on patients with lung cancer from 1993-2008. Methods: The proportions of enrollment onto SWOG lung cancer treatment trials by age (65-69, 70-79, ≥80 years) and gender were computed for 4-year time intervals between 1993 and 2008; corresponding rates in the US were derived from US Census and National Cancer Institute SEER data. Proportions in the SWOG trials were compared to the SEER proportions using a 1-sample binomial test of proportions. Time trends within SWOG were evaluated using linear regression. Results: The proportion of patients 65-69 was significantly higher than the US population between 1993 and 2004, but was not significantly different after 2004. Proportions of patients on SWOG trials 70-79 years old and ≥ 80 were significantly smaller than the US population. Females were underrepresented from 1993-2004. Between 2005 and 2008 female enrollment was not significantly different from the US population. Conclusions: Currently, the proportion of patients 65-69 years of age and of female gender enrolled in SWOG trials is representative of the general lung cancer population. Although some progress has been made in increasing trial participation of patients > 70, enrollment remains disproportionately low. The disparity is most evident in patients > 80. Continued efforts are needed to increase older patient participation in lung cancer trials. Supported in part by PHS Cooperative Agreement grants awarded by the National Cancer Institute: DHHS, CA32102 and CA38926. [Table: see text]
Prospective randomized phase II trial of oral vinorelbine (NVBo) and cisplatin (P) or pemetrexed (Pem) and P in first-line metastatic or locally advanced non-small cell lung cancer (M or LA NSCLC) patients (pts) with nonsquamous (non SCC) histologic type: NAVoTRIAL01—Preliminary results.
Authors: Bennouna Jaafar , Zatloukal Petr , Krzakowski Maciej Jerzy , Kollmeier Jens , Riviere Alain , Dansin Eric , Serke Monika , Favaretto Adolfo G. , Havel Libor , Malasse Stephanie , Biville-Hedouin Fabienne , Tan Eng Huat 
Published: March 2020

7575 Background: NVBo+P is considered as a standard treatment (trt) in M or LA NSCLC. The recent approval of Pem+P as front line chemotherapy (CT) for non-SCC demonstrates that today, histology could become a “new guidance” to treat patients (pts). Phase III trial (Scagliotti. JCO 2008) showed efficacy of Pem+P in patients with non-SCC pts. Moreover, the higher chemosensitivity of non-SCC is recognised and reported with other chemotherapies (Ardizzoni.JNCI 2007). In GLOB 3 study, NVBo+P also showed better survival in adenocarcinoma (11.7m) than in SCC (8.9m) (Tan.Ann of Oncol 2009). This trial was set up to assess the efficacy of NVBo+P compared to Pem+P for pts with non-SCC histological type. The primary end-point was disease control rate (DCR) including overall response rate (ORR) and stable disease (SD). Methods: Pts were randomised to receive NVBo 80 mg/m² D1D8 (60 at Cycle 1) + P 80 mg/m² D1 q3w or Pem 500 mg/m² + P 75 mg/m² D1 q3w. After 4 cycles of trt, for pts showing a disease control, single agent as continuation maintenance (CM) was proposed until progression or toxicity. Given that Pem+P is now considered as a reference trt in non-SCC, pts were randomised on a 2/1 basis and stratified according to stage (IIIB - IV - relapse), non-SCC confirmed by histology or cytology, gender, smoking status and centre. Results: From 10/09 to 02/11, 153 pts were randomised to receive NVBo+P (102 pts) or Pem+P (51 pts). The efficacy between the 2 arms is similar: The ORR/DCR (Recist 1.1) after 4 cycles of trt are 26%/75% in the NVBo arm (100 eval pts in ITT population) and 24%/78% in the Pem arm (50 eval pts in ITT population). At the end of December 2011, 7 patients are still treated in CM: 5 pts in the NVBo arm and 2 pts in the Pem arm. Conclusions: The 2 CT regimen, NVBo+P or Pem+P have a similar efficacy in terms of ORR/DCR for pts with advanced non-SCC NSCLC. These results appear to be in line with the published data. As the analysis is currently in progress, final results including safety data, PFS and OS will be presented during the meeting.
NGR-hTNF plus chemotherapy as first-line therapy of non-small cell lung cancer (NSCLC).
Authors: Gregorc Vanesa , Zilembo Nicoletta , Grossi Francesco , De Pas Tommaso M , Rossoni Gilda , Pietrantonio Filippo , Rijavec Erika , Giovannini Monica , Citterio Giovanni , Lambiase Antonio , Bordignon Claudio 
Published: March 2020

7581 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is a selective vascular targeting agent able to improve intratumoral chemotherapy uptake. Methods: Chemo-naive, stage IIIb-IV NSCLC patients (pts), stratified by histology (nonsquamous or squamous) and PS (0 or 1), were randomized to cisplatin 80 mg/m2/day(d)1 plus either pemetrexed 500 mg/m2/d1 (nonsquamous) or gemcitabine 1,250 mg/m2/d1+8 (squamous) every 3 weeks (q3w) up to 6 cycles with (arm A) or without (arm B) NGR-hTNF 0.8 μg/m2/d1 q3w until progression. Progression free survival (PFS) was primary end point of this phase 2 trial (β=20%, α=20%, HR=0.62, and n=102). Secondary end points included adverse events (AEs), response rate (RR) and overall survival (OS). Results: 59 pts were assigned to arm A and 57 to arm B. Baseline characteristics in arm A/B were: median age 62/63; male 34/37; PS 1 21/21; squamous 15/15; nonsmokers 14/12; EGFR mutations 5/5. For the nonsquamous group, 281 cycles (mean 6.5; range 1-18) were given in arm A and 190 (mean 4.7; range 1-6) in arm B, while for the squamous group, 88 (mean 6.3; range 1-19) in arm A and 48 (mean 3.7; range 1-6) in arm B. Most common grade 3/4 AEs were neutropenia 14% vs 17% and fatigue 7% vs 11% in arm A and B, respectively. No grade 3/4 AEs related to NGR-hTNF or bleeding in pts with squamous histology were noted. Median follow-up was 12.4 months. In the whole study population, median (m)PFS was 5.8 vs 5.7 months (HR=0.95), RR was 23% vs 19%, and 1-year OS was 62% vs 62% in arm A and B, respectively. In the nonsquamous subset, a trend toward longer mPFS in arm A compared to arm B was noted in pts with a PS of 1 (6.7 vs 4.6 months, respectively), nonsmoking history (6.2 vs 3.4), younger age (6.5 vs 3.4), and EGFR mutations (7.2 vs 3.3). In the squamous subset, mPFS was 5.1 vs 3.9 months (HR=0.71) and mOS was 14.2 vs 10.8 months (HR=0.73) in arm A and B, respectively. In these pts, ORR was 36% in arm A and 23% in arm B, while median changes from baseline in target tumor size after 2, 4, and 6 cycles were -29%, -45%, and -41%, respectively in arm A, and -18%, -22%, and -14%, respectively in arm B. Conclusions: Regardless of histology, NGR-hTNF can be safely given with standard chemotherapy, showing tolerability and hint of activity in squamous NSCLC.
Expression of folate pathway regulators and pemetrexed (pem) activity in patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Gianoncelli Letizia , Toschi Luca , Canal Barbara , Lo Russo Chiara , Rubino Luca , Finocchiaro Giovanna , Giordano Laura , Destro Annarita , Garassino Isabella M.G. , Cavina Raffaele , Siracusano Licia , Roncalli Massimo , Carbone Antonino , Santoro Armando 
Published: March 2020

7585 Background: Thymidylate synthase (TS) expression has been reported to predict pem activity in pts with advanced NSCLC. Besides TS, pem inhibits multiple enzymes of the folate pathway including dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GART) and aminoimidazole carboxamide ribonucleotide formyltransferase (AICAR). Aim of present study was to investigate whether these or other biomarkers influence pem activity in NSCLC pts. Methods: Advanced pretreated NSCLC pts who received at least two cycles of single agent pem were considered eligible if they had available tumor tissue to assess at least one of the proposed biomarkers. TS, DHFR, GART and AICAR protein expression was assessed by immunohistochemistry (IHC) in FFPE tumor samples. Pts were grouped as IHC+ and IHC– according to staining intensity. Additionally, presence of EGFR and KRAS mutations was investigated. Results: Ninety-six pts were included in the study. The majority of subjects was male (72%), smokers (93%), with adenocarcinoma (72%). Response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were 12%, 47%, 2.3 and 9.5 months, respectively. Most pts resulted TS-(72%), AICAR-(82%), DHFR+ (68%), GART- (61%). EGFR and KRAS mutations were identified in 15% and 25% of assessable cases. None of the biomarkers was significantly associated with pts characteristics (gender, histology, smoking status), nor with RR or DCR. GART- pts experienced longer PFS when compared with the GART+ group (HR 0.56, p=.052), while no difference was observed according to TS, DHFR and AICAR status. A significantly longer OS was observed for TS- (HR 0.52, p=.012), GART- (HR 0.50, p=.037) and AICAR- (HR 0.40, p=.028) pts. No significant difference in the distribution of EGFR mutant pts receiving EGFR TKIs after pem failure was observed between IHC+ and IHC- groups. Conclusions: Low TS, GART and AICAR protein expression predicts significantly prolonged survival in single agent pem-treated pts with advanced NSCLC. The lack of PFS difference according to TS and AICAR status suggests prognostic rather than predictive relevance for these biomarkers.
Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Socinski Mark A. , Langer Corey J. , Okamoto Isamu , Hon Jeremy K. , Hirsh Vera , Dakhil Shaker R. , Page Ray D. , Orsini James M. , Zhang Hui , Renschler Markus F. 
Published: March 2020

7590 Background: The median age of advanced NSCLC pts in the US is 71 years; yetelderly pts (≥70 years) are generally undertreated, with only ≈30% receiving systemic therapy. Hence, better, more tolerable therapeutic options are needed for this cohort. In a phase III trial nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, significantly improved ORR, the primary endpoint (25% vs 33%, P = 0.005), with a 1-month improvement in OS (P = NS) and improved safety. This analysis evaluated efficacy and safety in pts ≥70 and <70 years old. Methods: Pts with untreated stage IIIB/IV NSCLC and with an ECOG score of 0/1 were randomized 1:1 (stratified by age [≥70 vs <70 years], region, stage, gender, and histology) to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day 1 q 21 days. ORR and progression-free survival (PFS) were determined by blinded centralized review. Results: Of the phase III study population, 15% were elderly (156/1052; 74 pts in the nab-P/C and 82 in the sb-P/C arms). Most elderly pts were male (72%), Caucasian (71%), and had stage IV disease (64%). In pts both ≥70 and <70 years old, ORR was higher in the nab-P/C vs sb-P/C arm (≥70: 34% vs 24%, P = 0.196; <70: 32% vs 25%, P = 0.013). In pts ≥70 years old, PFS trended in favor of nab-P/C (median 8.0 vs 6.8 months, HR: 0.687, P = 0.134); OS was significantly improved (median 19.9 vs 10.4 months, HR: 0.583, P = 0.009). In contrast, PFS (6.0 vs 5.8 median months, HR: 0.903, P = 0.256) and OS (11.4 vs 11.3 median months, HR: 0.999, P = 0.988) were similar for both treatment arms in pts <70 years old. Adverse events were similar in pts ≥70 years old vs the entire study population, with less grade 3/4 neutropenia (P < 0.05) and neuropathy (P < 0.05) and increased thrombocytopenia (P = NS) and anemia (P < 0.05) in the nab-P/C vs sb-P/C arms. In pts ≥70 years old, patient-reported FACT-taxane subscales revealed significantly less neuropathy, pain, and hearing loss in the nab-P/C vs sb-P/C arms (P < 0.001). Conclusions: In elderly pts with advanced NSCLC, nab-P/C as first-line therapy was well tolerated and led to improved ORR and PFS, with significantly longer OS vs sb-PC.
Clinical benefit from pemetrexed before and after crizotinib exposure in patients with ALK positive non-small cell lung cancer (ALK+ NSCLC).
Authors: Berge Eamon , Delee Maxon , Lu Xian , Barón Anna E. , Solomon Benjamin J. , Doebele Robert Charles , Camidge D Ross 
Published: March 2020

7601 Background: Crizotinib (Criz) produces high response rates and prolonged progression free survival (PFS) in ALK+ NSCLC. Retrospective analyses suggest enhanced sensitivity to pemetrexed (Pem) in Criz-naïve ALK+ NSCLC. Different biological mechanisms of Criz resistance have recently been discovered. Clinical cross-resistance between Criz and Pem has not been previously investigated. Methods: Patients with stage IV ALK+ NSCLC treated in sequence with Pem then Criz (Pem-Criz), or Criz then Pem (Criz-Pem) were identified. Excluding CNS only progression events when no new systemic treated was started, PFS was compared using Cox Proportional Hazards. Correlations between molecular features of ALK positivity and Pem PFS were analyzed using Spearman correlations. Treatment sequence effect was explored using Fisher’s exact test. Results: We identified 19 Pem-Criz and 9 Criz-Pem ALK+ patients. Pem was given as monotherapy in 37% vs. 66%, and as median 2nd vs. 3rd line cytotoxic in the Pem-Criz and Criz-Pem groups, respectively. For the Pem-Criz group,median PFS was 8.9 months with Pem (range: 1-21.5 months), and 14.7 months with Criz (range:2.9+ -27.5 months). For the Criz-Pem group, median PFS was 8.4 months with Criz (range: 2-29 months), and 4.4 months with Pem (range: 0.5-10.5+ months). Patients were more likely to progress on Pem given after Criz than before, but confidence intervals were wide (HR 1.51, 95% CI 0.626-3.66). Neither native or rearranged signal copy number, nor percent cells ALK+ in the tumors correlated with PFS on Pem. Conclusions: Both Criz and Pem appear to be active drugs in ALK+NSCLC given in either order. Numerically, benefit from Pem was less when given post-Criz compared to pre-Criz, however this difference was not statistically significant. Several potential confounders exist in our small dataset (notably differences in line of therapy and use in combo vs. monotherapy). To fully address whether there may be a significant difference in overlap of induced specific drug resistance mechanisms, the clinical effect of Criz/Pem sequencing should be explored in a larger series adjusting for confounding effects.
A first-in-human phase I/II study of ALK inhibitor CH5424802 in patients with ALK-positive NSCLC.
Authors: Kiura Katsuyuki , Seto Takashi , Yamamoto Nobuyuki , Nishio Makoto , Nakagawa Kazuhiko , Tamura Tomohide 
Published: March 2020

7602 Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase constitutively activated in a subset of non-small cell lung cancer (NSCLC) following chromosomal gene translocation. CH5424802 was identified as a potent, selective, and oral ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against NSCLC cells expressing EML4-ALK fusion in vitro and in vivo (Cancer Cell, 2011). Our results support the potential of CH5424802 as a new therapeutic opportunity for patients (pts) with ALK-positive NSCLC. Methods: Pts with ALK-positive NSCLC received CH5424802 twice daily orally until progressive disease or toxicity was observed. In the phase I portion, dose was escalated using an accelerated titration scheme. The primary objectives were to investigate the safety, tolerability and pharmacokinetic (PK) parameters under fasting conditions, and to determine the recommended dose (RD) for use in the phase II portion. The primary objectives of the phase II portion were to investigate the efficacy and safety at the RD. The phase I portion was amended to include an investigation under non-fasting conditions in addition to fasting conditions. Results: 15 pts (M/F: 9/6) were treated with CH5424802 under fasting conditions in 6 cohorts (20 mg bid to 300 mg bid) and 9 pts (M/F: 2/7) were treated under non-fasting conditions in 2 cohorts (240 mg bid and 300 mg bid). Median age was 42.5 years. The highest dose level defined in the protocol (300 mg bid) did not reach the MTD. Thus, a DLT was not determined. Toxicities were mild to moderate. The most frequent toxicity was grade 1 myalgia. Grade 3 toxicity (cases) occurred as follows; hypophosphatemia (2), neutropenia (2), blood CPK increased (1) and hypermagnesemia (1). PK data from the fasting cohorts showed dose-dependent increases of Cmax and AUC. All pts at all dose levels achieved tumor regression. At dose levels 240 mg bid or more under fasting conditions, all 7 pts with measurable lesions achieved a partial response. So far, 11 pts have been on study treatment ≥ 6 months. Conclusions: CH5424802 was well tolerated with promising efficacy in pts with ALK-positive NSCLC. The phase II portion is ongoing.
Metastatic NSCLC: Treatment patterns, outcomes, and costs of newer agents.
Authors: Sacher Adrian G. , Le Lisa W. , Lau Anthea , Earle Craig , Leighl Natasha B. 
Published: March 2020

7606 Background: New therapies for metastatic NSCLC have improved survival in clinical trials. The increased cost of these agents has led to variable drug funding and treatment across jurisdictions. Here we review patterns, real-world outcomes and costs of metastatic NSCLC treatment in the province of Ontario. Methods: All patients diagnosed with metastatic NSCLC from 2005-2009 were identified from the Ontario Cancer Registry with demographic, histologic and mortality data. Treatment records from the Ontario New Drug Funding Program and centralized treatment database were linked. Statistical analysis involved Wilcoxon rank sum, Kruskal-Wallis, Cochran-Armitage trend and likelihood ratio tests where appropriate. Results: 8113 metastatic NSCLC patients were identified. The median age was 68; 39% had adenocarcinoma, 14% squamous carcinoma and 43% histology not otherwise specified. Most were treated in regional cancer centers (92%). The majority (76%) did not receive systemic therapy; 23% received first-line chemotherapy, most commonly platinum doublets. More patients received systemic therapy over time (19% in 2005 v 26% in 2009, p <0.0001). Older patients (p <0.0001) and those with squamous histology (p <0.0001) were less likely to receive systemic therapy. Center of diagnosis did not affect the likelihood of treatment (p=0.46). The median time from diagnosis to death was significantly greater among patients selected to receive chemotherapy (9.3 v 3.2 months, p <0.0001), and with cisplatin/gemcitabine compared to other doublets (10.7 v 8.2 months, p=0.004). 31% of treated patients received second-line chemotherapy, predominantly with docetaxel (52%) or pemetrexed (41%). Pemetrexed use increased significantly over time (8% in 2005 v 71% in 2009, p<0.0001), as did the mean drug cost of second-line therapy ($5939/patient in 2005 v $10,057 in 2009). A longer median survival was also seen with pemetrexed in adenocarcinoma (17.9 v 15.2 months for docetaxel, p =0.02). Conclusions: Most metastatic NSCLC patients do not undergo systemic treatment. First- and second-line treatment outcomes in this population-based study were similar to clinical trials, confirming better outcomes with new agents at greater cost.
Three-year survival in stage IV non-small cell lung cancer (NSCLC): The importance of metastatic distribution.
Authors: Karp Daniel D. , Hanneken Jan M , Taylor Sarah H , Men Taoyan , Wu Xifeng , Pu Xia 
Published: March 2020

7608 Background: Although long term survival (LTS) is an important goal of lung cancer treatment, those with metastatic disease at presentation have a median of only 8-9 months in most series with a small “tail” on the survival curve. We analyzed a large cohort of Stage IV pts by performance status (PS), smoking history, number and sites of disease to assess factors associated with 36 month survival. Methods: From 2004–2008, 526 newly diagnosed untreated pts with Stage IV NSCLC received initial treatment at our institution. Sites of disease were analyzed according to lung, brain, bone, liver, adrenal, skin, malignant effusion, lymphangitic, bulky pleural disease, and “other”. No patient had definitive surgery. Results: Overall, 58/526 pts (10.8%) survived 36 months or more. 453 pts died within 36 months. 15 pts alive with follow-up time less than 36 months were removed from further analysis. Of those, 38/58 (65.5%) had only 1 metastatic site (p<0.001). 14 (24.1%) had 2 sites, only 6 (10.3%) had 3 or more sites. Those 19 pts with lung to lung spread were the most common (32.8%) with LTS – reflecting the M1 status in the new International Staging System. Only 1 LTS pt had liver mets at diagnosis – a solitary lesion treated with radiofrequency ablation. 20 pts had PS=0 (0.019) and 29 had PS=1 (NS). PS=2 pts made up 6. 2 pts had PS=3 initially. 1 unknown. Only 6/58 (10.3%) were current smokers, 23 (39.7%) were never-smokers (p<0.001). Adenocarcinoma made up 65.5%. Conclusions: Progress in lung cancer survival has been slow. Very few LTS pts have more than 1 site of metastatic disease at presentation, virtually none with liver disease (p=0.02). Number of metastatic sites and presence of liver metastases appear to be important stratification variables for lung cancer clinical trials.