bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of a TGF-β2 antisense gene modified allogeneic tumor cell vaccine (Lucanix) in advanced NSCLC
Authors: Nemunaitis J. J. , Dillman R. O. , Schwarzenberger P. , Senzer N. , Tong A. , Devol E. , Chamberlin T. , Shawler D. , Fakhrai H. 
Published: March 2020

7018 Background: Lucanix (L) is a non-viral gene based allogeneic tumor cell vaccine which demonstrates enhancement of tumor antigen recognition as a result of Transforming Growth Factor (TGF-β2) inhibition. Methods: We performed a randomized dose variable phase II trial involving stage IIIB/IV non small cell lung cancer (NSCLC). Each patient received one of 3 doses (1.25, 2.5, 5.0x107 cells/injection) of L, given intradermally, to a maximum of 16 injections either monthly or every other month. Immune function, safety and anticancer activity were monitored. Results: Sixty-one patients (15 IIIB/ 46 IV; 51/61 (84%) ≥ prior cytotoxic therapy), received a total of 417 vaccinations. No significant (≥ grade 3) adverse events probably or definitely associated with administration of the vaccine were observed. A dose-related survival difference was demonstrated in patients who received ≥ 2.5 × 107 cells/injection versus those who received <2.5 × 107 cells/injection (p=0.0151). The percent of patients surviving 1 and 2 years was 61% and 52% for the high dose group and 40% and 13% for the low dose group. Fifteen percent of patients achieved a partial response. Cytokine production (IFN-γ, p=0.006; IL-6, p=0.004; IL4, p=0.007) was induced, antibody mediated response to vaccine HLA antigen was observed (p=0.014) and cell mediated response showed a correlation trend (p=0.086) in patients achieving stable disease or partial response (15%) compared to those with progressive disease. Conclusions: In conclusion, L is safe and well tolerated. A survival advantage is suggested in patients who receive ≥ 2.5x107 cells/injection thereby supporting the justification for further phase III evaluation. Phase III investigation is recommended. [Table: see text]
Routine positron emission tomography (PET) and selective mediastinoscopy is as good as routine mediastinoscopy to rule out N2 disease in non-small cell lung cancer (NSCLC)
Authors: Serra M. , Cirera L. , Rami-Porta R. , Bastus R. , Gonzalez S. , Simó M. , Domenech M. , Barbeta E. , Soler J. M. , Belda J. 
Published: March 2020

7031 Background: To evaluate the presence of mediastinal lymph node spread of NSCLC after changing the clinical staging protocol from routine to selective surgical mediastinal exploration (SME) based on PET. Methods: From 1994 to 2003, routine SME (mediastinoscopy, parasternal mediastinotomy or extended cervical mediastinoscopy) was performed to 655 patients (pts) with NSCLC as the last clinical staging procedure prior to thoracotomy. Those with no mediastinal involvement underwent thoracotomy with lung resection (T) and systematic nodal dissection (SND). From 2004, PET was routinely done in 90 pts and SME was reserved for those with positive mediastinal or hiliar uptake on PET, mediastinal lymph node diameter greater than 1cm in shorter axis on computerized tomography, and in tumors contacting with the mediastinum. All other pts and those with negative SME underwent T and SND. Results: Among 655 pts studied between 1994 and 2003, 236 (36%) had positive SME; 419 underwent T and SND and 40 (6.1%) were classsified as pN2. Of the 90 evaluable pts with PET, 27 had increased uptake in the mediastinum an 17 had positive SME; the remaining 10 ptes with negative SME underwent T and SND and 7 of them were found to have no nodal disease (false positive PET), but three of them were found to have nodal disease. Of the 63 pts with no uptake in the mediastinum, 29 underwent SME for reasons stated above: 5 SME was positive; in 24 SME was negative and the patients underwent T and SND: 21 were pN0 and 3 were pN2. Only 1 tumor of the remaining 34 pts with negative PET who underwent T and SND without SME was classified pN2. Additionally, in 1 pt PET detected N2 disease but not N3. 4 (4.5%) pts with pN2 disease were clinically understaged (negative PET and negative SME) and underwent thoracotomy. 3 pts with positive PET who underwent SME were classified pN0, but they were pN2 (false negative SME). In total, 7 (7.8%) pts with pN2 disease were clinically understaged and underwent T. This rate is not statisticallly different from the 6.1% pN2 tumor found after routine SME. Conclusions: In this preliminary study, this new clinical staging protocol with routine PET and selective SME saves up to 35% of SME and yields a similar rate of pN2 disease compared to routine SME. No significant financial relationships to disclose.
ECOG 4599 phase III trial of carboplatin and paclitaxel ±bevacizumab: Subset analysis of survival by gender
Authors: Brahmer J. R. , Gray R. , Schiller J. H. , Perry M. , Sandler A. , Johnson D. 
Published: March 2020

7036 Background: E4599 compared carboplatin and paclitaxel (PC) versus carboplatin, paclitaxel, and bevacizumab (PCB) in patients with advanced stage non-small cell lung cancer. Survival was superior with PCB. However, an unplanned subset analysis did not show a survival benefit for women in the PCB arm. Methods: Patients (pts) in the E4599 database were divided into male (M) and female (F) cohorts by assigned treatment. Survival was calculated separately for each cohort. Known prognostic factors and toxicities were compared by gender. Proportional hazards models (PHM) of survival with multiple factor combinations were fit to adjust for treatment effect for sex, performance status, stage, liver, bone and adrenal involvement, measurable disease, prior radiation therapy, weight loss ≤ 5% and to examine the difference in treatment effect by sex. Results: The analysis includes 850 patients. The median survival for M is 8.7 months (mo) (PC) versus (vs) 11.7 mo (PCB) (p=0.001). The median survival for F is 13.1 mo (PC) vs 13.3 mo (PCB) (p=0.87). On PCB, progression free survival (PFS) for M and F is 6.3 mo and 6.2 mo respectively. Response rate (RR) is 23.6% for M and 38.5% for F. Duration of response is 6.8 mo for both. No demographic differences exist between the two arms for M. A higher proportion of F on the PCB arm have liver metastasis (PCB 23.2% vs PC 11.7%, p=0.003). On the PC arm, the febrile neutropenia rate is higher for M (M 3.1% vs F 0%, p=0.02). On the PCB arm, the adverse events with a gender difference are severe hypertension (M 4.2%, F 9.9%, p=0.02), constipation (M 1.4%, F 4.7%, p=0.05), and abdominal pain (M 0.9%, F 5.2%, p=0.01). The test for a treatment by sex interaction in a PHM for survival has p = 0.04. In the PHM adjusting for the other factors, the estimated treatment hazard ratios are 0.73 for M and 0.97 for F and the test for a sex by treatment interaction has p=0.09. Conclusions: Women on the PCB arm vs the PC arm appear not to have a survival advantage. Reasons for this remain unclear. However, the addition of bevacizumab does result in significant improvements in RR and PFS, arguing in favor of an overall treatment benefit. Further analysis of other demographic information (tumor type and second-line therapy) is ongoing. [Table: see text]
Chemoradiotherapy (CRT) and gefitinib (G) in stage III non-small cell lung cancer (NSCLC): A CALGB stratified phase II trial
Authors: Ready N. , Janne P. , Herndon J. , Bogart J. , Crawford J. , Edelman M. , Wang X. , Gu L. , Green M. R. , Vokes E. E. 
Published: March 2020

7046 Background: G is a small molecule inhibitor of EGFR with activity in advanced NSCLC and preclinical evidence of being a radiosenitizer. Methods: Patients with stage III NSCLC were assigned to stratum 1 (PS 0–1>5% weight loss and/or PS 2) or stratum 2 (PS 0–1weight loss < 5%). Both strata received induction paclitaxel (P) 200 mg/m2 and carboplatin (C) AUC of 6 IV every three weeks for 2 cycles plus G 250 mg PO/day. G was removed 4/05 from induction therapy as stage IV studies showed no benefit from adding G to P and C. Stratum 1 then received RT 200 cGy for 33 fractions (total dose 6,600 cGy) and G 250 mg PO /day. Stratum 2 received the same RT with concurrent G 250 mg/day, and P 50 mg/m2 plus C AUC of 2 weekly for 7 doses. Maintenance G was started after all toxicities were grade ≤2. Results: Activation was 5/02 and administrative closure 5/04 due to results from SWOG S0023. 64 patients were accrued and 59 (20 stratum 1, 39 stratum 2) were eligible and analyzed: median age 67, male 74%, adeno 30%, squamous 45%, other 25%, IIIA 51%, IIIB 49%. There was no clear increase for acute high-grade infield toxicities compared to CRT alone (reported PASCO 2004). Best response for stratum 1 was PR 29% for induction (RR 29%, 95% CI 10%-56%) and CR 5%, PR 45% full treatment (RR 50%, 95% CI 27%-73%); for stratum 2 PR 13% for induction (RR 13%, 95% CI 3%-34%) and CR 5%, PR 76% full treatment (RR 81%, 95% CI 65%-92%). Stratum 1 “poor risk” median failure free survival (FFS) was 11.5 months (95% CI 5.6–21.2), one year survival 60% (95% CI 33%-79%) and median overall survival (OS) 19.0 months (95% CI 7.2–21.2). Stratum 2 “good risk” median FFS was 9.2 months (95% CI 6.7–12.0), one year survival 47% (95% CI 30%–63%) and median OS was 12.0 months (95% CI 8.5–18.6). EGFR and Ras mutation analysis on tumor biopsies (n = 50) will be presented. Conclusions: Small sample size prevented planned data analysis. Survival of “good risk” patients on stratum 2 (CRT + G) was disappointing. The promising survival of the small number of “poor risk” patients on stratum 1 (RT + G) justifies a follow-up phase II trial of induction chemotherapy followed by RT with a concurrent small molecule EGFR inhibitor. [Table: see text]
The quantification of the catalytic subunit of telomerase in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients
Authors: Sirera R. , Camps C. , Llobat L. , Berrocal A. , Bremnes R. M. , Blasco A. , Juarez A. , Taron M. , Sanchez J. J. , Rosell R. 
Published: March 2020

7052 Background: Qualitative and quantitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the free amount in plasma of the catalytic subunit of telomerase (hTERT) and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the serum using commercial adsorption columns. The amount of free hTERT in plasma was quantified by using RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Median hTERT value was 4856 ng/ml; for patients in IIIB was 4847 ng/ml [263–964826] and 4886 ng/ml [67–4373520] in stage IV (p = 0.75). There was not association between hTERT values and response to therapy, 20588 ng/ml [122–317251] in the CR+PR group vs 50204 ng/ml [67–4373520] in the SD+PD group (p = 0.09). hTERT values were not related with the localization of the metastasis. Dividing the cohort in two sets according to hTERT median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with hTERT <4856 ng/ml had a median TTP of 5.3 months (m) [4.4–6.1] while for hTERT >4856 ng/ml was 4.1 m [3.5–4.6], (p = 0.0009). OS when hTERT <4856 ng/ml was 10.1m [4.9–11.3] and for hTERT >4856 ng/ml was 8.4 m [7.2–9.5], (p = 0.01). In the multivariate analysis, hTERT was an independent predictive variable for TTP (HR 1.39, CI 95% 1.1–1.7, p = 0.002) and OS (HR 1.27, CI 95% 1.1–1.6, p = 0.04). Conclusions: In advanced NSCLC patients, the quantification of free circulating hTERT in plasma is an affordable and valuable prognostic marker. High plasma hTERT levels are a poor prognostic indicator for TTP and OS. No significant financial relationships to disclose.
Clinical outcome of gemcitabine (gem)/cisplatin (cis)- vs docetaxel (doc)/cis-treated stage IV non-small cell lung cancer (NSCLC) patients (p) according to X-ray repair cross-complementing group 3 (XRCC3) polymorphism and age
Authors: Rosell-Costa R. , Alberola V. , Camps C. , Lopez-Vivanco G. , Moran T. , Etxaniz O. , De Las Peñas R. , Gupta J. , Taron M. , Sanchez J. 
Published: March 2020

7055 Background: Significant interaction between XRCC1 genotype and age has been reported, with younger subjects having a greater risk of developing lung cancer. Carriers of XRCC3 241 MetMet have higher levels of DNA adducts, leading us to hypothesize that they would be more chemosensitive, especially younger patients. Methods: Real-time PCR assay was used to determine XRCC3 genotype from DNA isolated from baseline blood samples of 878 stage IV NSCLC p (162 treated with gem/cis; 716 with doc/cis). Median age, 60; 266 p (30%) <55; 239 p (39%) 55–66; 273 p (31%) >66. Adenocarcinoma: 459 p (53%). Homozygous variant XRCC3 241 MetMet was found in 124 p (14%), with the same frequency in each of the three age groups. Results: After a median follow-up of 7.6 months (m) (95% CI, 1–47 m), overall median survival (MS) was 9.5 m (95% CI, 8.8–10.2 m), with no differences between the 2 regimens. In all p with XRCC3 241 MetMet, MS was 12.9 m for p treated with gem/cis and 8.4 m for p treated with doc/cis (P = 0.06) (hazard ratio at 2 y = 0.23). In p with XRCC3 241 MetMet <55 y, MS was not reached for p treated with gem/cis and 9.2 m for p treated with doc/cis (P = 0.02), which translated into a 60% difference in survival at 2 y. This difference diminished in p with XRCC3 241 MetMet 55–66 y (MS 12.9 m with gem/cis, 6.9 m with doc/cis [P = 0.09]; 28% difference in survival at 2 y) and disappeared in p >66 y (MS 5.8 m with gem/cis, 7.8 m with doc/cis [P = 0.55]. For the other XRCC3 241 genotypes (ThrThr and ThrMet), no differences in MS were found either overall or broken down by age. Conclusions: XRCC3 241 MetMet is both an easily assessable and robust predictive marker for survival in younger gem/cis-treated NSCLC p. The survival benefit dwindles with increasing age, possibly related to the enhanced DNA repair capacity of older p. No significant financial relationships to disclose.
Phase I study of irinotecan (Ir) and cisplatin (DDP) in combination with thoracic radiotherapy (RT), either twice daily (45 Gy) or once daily (70 Gy), in patients with limited (Ltd) small cell lung carcinoma (SCLC): Early analysis of RTOG 0241
Authors: Langer C. J. , Swann S. , Werner-Wasik M. , Lilenbaum R. , Curran W. , Sandler A. , Scidmore N. , Samuels M. , Choy H. 
Published: March 2020

7058 Background: Ir in combination with DDP has proven superior to DDP & VP-16 in extensive stage SCLC (Noda et al NEJM 1/02), with marked increase in 2 yr survival (19.5%, vs 5.2%). Hence, it is critical to determine if Ir can be safely & effectively integrated with concurrent RT and DDP in earlier stage, Ltd SCLC. Methods: 1° endpoint: Determine maximum tolerated dose (MTD) of Ir d 1 & 8 plus DDP 60 mg/m2 q 3 wks & either BID RT (45 Gy) or QD RT (70 Gy). Eligibility stipulated Tx-naïve patients (pts) with Ltd SCLC, PS 0–1, adequate heme (ANC ≤ 1500/mL; plts ≥ 120,000/mL) hepatic (bili ≤ 1.5/dL) & renal (creat ≤ 1.5gr/dL) function, & baseline FEV1 of ≥ 1 liter. Ir was escalated in sequential (seq) cohorts from 40 mg/m2 (level 1) to 50 mg/m2 (level 2) & then to 60 mg/m2 (level 3) d 1 & 8 q 3 wks during each cycle of treatment. Ir & DDP were given concurrently with RT for cycle 1 in seq A (45 Gy) & during cycles 1 & 2 in seq B (70 Gy). 36 pts were targeted for accrual. DLT was defined as gr 4 esophagitis, pneumonitis, or diarrhea; gr 4 neutropenic fever, or any attributable gr 5 toxicity Results: As of 12/05, 36 pts were accrued, (21 - seq A; 15 - seq B). Median age was 64 (range 49–79) Of 33 eval pts, 18 (55%) were female; 24 (73%) PS 0; 67% had ≤ 5% wt loss. Attributable DLT was not seen in seq A, but was observed in seq B (70 Gy) at 50 mg/m2 with 1 episode each of gr 4 diarrhea & esophagitis, necessitating hospitalization. In addition, 1 pt in seq B had non-attributable gr 4 cardiovascular AEs. There has been no acute gr 5 toxicity. 1 pt experienced late gr 3 pulm toxicity, another gr 3 constitutional toxicity, including wt loss. The overall incidence of gr 3 esophagitis was 34%. Conclusions: In Ltd SCLC, I at 60 mg/m2 d 1 & 8 is safe & feasible in combination with DDP 60 mg/m2 q 3 wks & BID RT (45 Gy). The MTD for I in combination with RT (70 Gy) & DDP 60 mg/m2 is 40 mg/m2 d 1 and 8. Response, progression, survival data remain immature. [Table: see text] [Table: see text]
Phase II study of amrubicin, a new active drug in refractory or relapsed small-cell lung cancer (SCLC): Thoracic Oncology Research Group Trial 0301
Authors: Seto T. , Masuda N. , Takiguchi Y. , Isobe H. , Okamoto H. , Ogura T. , Yokoyama A. , Watanabe K. , Eguchi K. 
Published: March 2020

7060 Background: Amrubicin, a totally synthetic 9-aminoanthracycline, is a topoisomerase II inhibitor. The response rate to amrubicin at 45 mg/m2 on days 1–3 in chemotherapy-naive patients with extensive stage SCLC was 75.8% on an intent-to-treat analysis, with major dose-limiting toxicities of neutropenia, anemia, thrombocytopenia, and anorexia. The very high activity of amrubicin as a single agent in this disease led us to carry out the phase II trial reported here, which was designed to determine the antitumor activity and toxicity of amrubicin in previously treated pts with SCLC. Methods: Pts with cytologically or histologically proven SCLC who were previously treated with at least one platinum-based chemotherapy and ECOG PS 0–2 were eligible. They received amrubicin 40mg/m2 intravenously on days 1–3 every 3 weeks. The primary end-point was the response rate, which determined the sample size of 44 pts in the sensitive cases and 15 pts in the refractory cases, respectively. Secondary objectives were to determine the progression-free survival, overall survival, and 1-year survival rate. Results: In total, 60 pts consisting of 44 sensitive cases and 16 refractory cases with median age 67 years (range 52–79) and 46 out of 60 male were enrolled. The median treatment cycles were 4 (1–8). Grade 3/4 hematological toxicity per patient (pt) was neutropenia (83%), thrombocytopenia (20%) and anemia (33%). Febrile neutropenia was observed in 3 pts. Grade 3/4 non-hematological toxicity per pt was pneumonia (3%), anorexia (15%), low Na levels (8.3%), pneumonitis (1.7%) and cerebral hemorrhage (1.7%). No treatment-related death was observed. The overall response rates were 52% (95% CI: 37–68) in the sensitive cases, and 50% (95% CI: 25–75) in the refractory cases. The progression-free survival, overall survival and 1-year survival in the sensitive cases and the refractory cases were 4.0 and 3.2 months, 11.7 and 10.9 months and 48.2 and 37.8%, respectively. Conclusions: Amrubicin has a significant activity in SCLC, particularly in pts refractory to prior chemotherapy, with predictable and manageable toxicities. Further studies to evaluate the survival benefit of amrubicin in this setting are warranted. No significant financial relationships to disclose.
A phase II, multicenter, randomized clinical trial to evaluate the efficacy and safety of bevacizumab in combination with either chemotherapy (docetaxel or pemetrexed) or erlotinib hydrochloride compared with chemotherapy alone for treatment of recurrent or refractory non-small cell lung cancer
Authors: Fehrenbacher L. , O’Neill V. , Belani C. P. , Bonomi P. , Hart L. , Melnyk O. , Sandler A. , Ramies D. , Herbst R. S. 
Published: March 2020

7062 Background: Bevacizumab is a recombinant, humanized anti-VEGF MAb. Erlotinib is a potent, reversible, highly selective and orally available EGFR tyrosine-kinase inhibitor. Both compounds have demonstrated a survival benefit in the treatment of NSCLC: bevacizumab when added to chemotherapy in the first line setting, and erlotinib when given alone in the 2nd/3rd line. In addition, a single arm phase I/II study of the combination of bevacizumab and erlotinib has shown encouraging survival and response rate data, with a favorable safety profile (Sandler et al, PASCO 2004). Methods: A multicenter, randomized phase II trial was conducted to evaluate the safety of combining bevacizumab with chemotherapy (docetaxel or pemetrexed), or with erlotinib; and to make a preliminary assessment of the efficacy of combining bevacizumab with chemotherapy or erlotinib relative to chemotherapy alone, as measured by progression-free survival. All patients had histologically confirmed non-squamous NSCLC and had experienced disease progression (clinical or radiological) during or following one platinum-based regimen for advanced stage disease. Randomization was on a 1:1:1 basis to docetaxel or pemetrexed plus placebo (arm 1) v docetaxel or pemetrexed plus bevacizumab (arm 2) v bevacizumab plus erlotinib (arm 3). Patients remained in the treatment phase of the study until documented radiographic or clinical disease progression or through 52 weeks of study treatment. Results: Between August 2004 and November 2005, 120 patients were randomized and treated. To date, there have been 68/85 required PFS events; arms 1 and 2 therefore remain blinded. Demographics from the first 85 patients for arms 1 & 2 v 3 are as follows: median age 65 v 68;% male/female 64/36 v 44/56; ethnicity % white/black/asian/other 83/12/2/3 v 74/15/4/7; % ECOG PS 0/1/2 46/52/2 v 50/50/0; % adenocarcinoma/BAC&BAC-like/Other 67/7/26 v 69/8/23; % current/previous/never-smoker 15/71/14 v 11/74/15. Conclusions: Efficacy and safety results will be presented at the meeting. [Table: see text]