bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational research (TR) results from pointbreak: A randomized, open-label, phase III study of pemetrexed (Pem)+carboplatin (Cb)+bevacizumab (Bev) followed by maintenance pem+bev (Pem Arm) versus paclitaxel (Pac)+cb+bev followed by maintenance bev (Pac Arm) in patients (pts) with stage IIIB or IV nonsquamous non-small cell lung cancer (ns-NSCLC).
Authors: Garon Edward B. , Patel Jyoti D. , Myrand Scott , Nguyen Tuan , Reynolds Craig H. , Spigel David R. , Hermann Robert C. , Liu Jingyi , Guba Susan C. , Govindan Ramaswamy , Socinski Mark A. , Bonomi Philip 
Published: March 2020

8086 Background: Results of PointBreak were previously reported. Correlative tissue TR results are presented. Methods: Of 939 pts in the intent-to-treat population (ITT), 211 (22.5%) signed TR consent forms and had evaluable samples. Specimens were analyzed for: Epidermal Growth Factor Receptor (EGFR) mutations by polymerase chain reaction (n=132); thyroid transcription factor-1 (TTF-1) (n=205), thymidylate synthase (TS) (n=189), and folate receptor-alpha (FR-α) (n=180) by immunohistochemistry (IHC) (H-scores range, 0-300). H scores were dichotomized based on positive (>0)/negative (=0) cutpoint. Adjusted Cox/logistic regression determined correlations between overall survival (OS), progression-free survival (PFS), response rate (RR), and dichotomous IHC markers. A 2-sided test with α = 0.05 and 0.1 evaluated treatment and interaction effects, respectively. Results: Median (m) OS and mPFS were similar in the ITT and TR populations for both arms. 11/132 (8.3%) pts had activating EGFR mutations. For TS or FR-α, no significant between-arm differences in OS, PFS and RR were seen. 139/205 (67.8%) pts had positive TTF-1 (TTF-1+). TTF-1+ pts, compared with TTF-1-, independent of treatment, had significantly longer mOS (14.9 vs 8.7 mos, HR 0.48, p<0.001), mPFS (6.9 vs 4.5 mos, HR 0.62, p=0.006), and higher RR (38.9% vs 19.7%, OR 2.68, p=0.008). For TTF-1+ pts, compared with Pac arm, Pem arm had longer mOS (17.6 vs 12.8 mos, HR=0.7, p=0.08; interaction p=0.12) and mPFS (7.3 vs 5.8 mos, HR=0.78, p=0.20; interaction p=0.261); although not statistically significant. Conclusions: The number of pts with EGFR mutations was too small to draw conclusions. No significant between-arm differences for TS and FR-α were seen. Longer survival in TTF-1+ pts suggests TTF-1 expression is prognostic. Additional studies will be needed to better understand trends favoring pem for survival among TTF-1+ pts and other prognostic and/or predictive relationships of these markers. Clinical trial information: NCT00762034.
Patterns of second-line chemotherapy and its effect on survival in patients treated within the Veterans Health Administration (VHA).
Authors: Santana-Davila Rafael , File Danielle M. , Arce-Lara Carlos Eduardo , Kelley Michael J. , Williams Christina D. , Whittle Jeffrey C. 
Published: March 2020

8090 Background: Second-line chemotherapy (2-L) improves overall survival (OS) in patients with metastatic NSCLC. In 2004, erlotinib and pemetrexed were approved as 2-L agents. In this study we analyze the utilization of anti-cancer agents and survival for patients with NSCLC who received 2-L treatment within the VHA. Methods: We identified from the VA Central Cancer Registry incident cases of metastatic NSCLC diagnosed between 2001 and 2008. We included patients who received their 1st cycle of chemotherapy within 120 days of diagnosis. A chemotherapy regimen included all chemotherapy agents prescribed during the next 28 days. We defined a subsequent line of therapy when a new agent was started after a period of more than the initial 28 days since the last drug. We divided our cohort into two based on whether they were diagnosed or treated before August of 2004 (the date pemetrexed was approved). Results: 5,893 patients fulfilled our eligibility criteria and were included for analysis. 2,200 patients were diagnosed before 2004 and 3,693 after. 2-L was administered in 35% (n=2052) of patients overall. Veterans diagnosed after 2004 were more frequently prescribed 2-L compared to those diagnosed earlier (30.2 vs. 37.6%, p<0.001). The most commonly prescribed agent in the earlier period was docetaxel in 43% (n=226) followed by gemcitabine in 22% (n=115). In contrast for patients treated after 2004 the most common agents were pemetrexed in 28% (n=421) followed by erlotinib in 27% (n=418). In this period docetaxel and gemcitabine was prescribed in 19 and 10% of cases respectively. Time from diagnosis to the start of 2-L was shorter in patients treated before 2004 (median 3.6 months (IQR 2.3-6.9) vs. 4.9 (IQR 2.6-8.2) p<0.001). Third-line chemotherapy was administered more frequently in those patients treated after 2004 (26 vs. 5.9%, p<0.001). There was no difference in survival between the two periods (Median OS 5.8 vs. 5.6 months in patients treated after 2004p=0.73) Conclusions: Since 2004 with the introduction of two new agents, which were widely adopted, patients are more likely to receive 2-L for NSCLC. In the last decade there has been no improvement in OS for patients treated with 2-L.
Randomized phase II study of pharmacodynamic separation (PDS) of pemetrexed (Pem) and erlotinib (Erl) versus pem alone in patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Li Tianhong , Piperdi Bilal , Walsh William Vincent , Kim Mimi , Gucalp Rasim , Haigentz Missak , Bathini Venu Gopal , Wu Xiaoxia , Pasquinelli Patricia , Gajavelli Srikanth , Sreedhara Meera , Beckett Laurel A , Lara Primo , Gandara David R. , Perez-Soler Roman 
Published: March 2020

8097 Background: Preclinical and phase I studies showed that PDS optimizes cytotoxicity of concurrent EGFR inhibitors and chemotherapy. We conducted a randomized phase II trial to assess relative efficacy of Pem alone (Arm A) versus Pem +Erl on a PDS dose-schedule (Arm B) as 2nd-line therapy in pts with advanced NSCLC (NCT00950365). Methods: Eligible pts were randomized 2:1 (Arm B: A), stratified by sex, smoking history, and performance status (0/1 vs 2). Accrual was restricted to non-squamous histology in 2009. Treatment: Arm A – Pem 500 mg/m2IV on day 1; Arm B – Pem + Erl 150 mg po QD on days 2-17. 1 cycle = 3 weeks. Primary endpoint was progression-free survival (PFS). 50 pts in Arm B were needed to detect an increase in median PFS from ~3 to 4.5 months. Results: 83 pts were entered. Age: 63 yo. Female: 42 (53%). Smoking ≥15PY: 58 (72%). Nonsquamous: 78 (99%). The primary endpoint of the study was met: Efficacy results from 79 eligible pts showed 1.6-fold longer PFS in Arm B (4.6 m) compared to Arm A (2.8 m). Although the study was not designed to directly compare two arms, p value was 0.052. Toxicity: G3/4 Hem (A/B): 8(30%)/12(23%); Neutropenia with infection (A/B): 0/3(6%). G3/4 Non-Hem (A/B): skin rash: 0/3(6%); diarrhea: 0/2(4%); joint pain: 1(4%)/6(11.5%). Treatment related death (A/B): 0/1. Interstitial lung disease (A/B): 0/1. Conclusions: PDS of Pem and Erl is well tolerated and has promising clinical activity in 2nd-line non-squamous NSCLC. Ongoing correlative studies aim to identify a subgroup of patients who might benefit most from this treatment, which will guide the design of a confirmatory phase III study. (UL1 RR024146, P30CA093373, Lilly, Astellas) Clinical trial information: NCT00950365. [Table: see text]
A French multicentric and prospective validation study for ALK translocation diagnosis in lung adenocarcinomas.
Authors: Lantuejoul Sylvie , Rouquette Isabelle , Begueret Hugues , Blons Helene , Penault-Llorca Frederique , Copin Marie-Christine , Antoine Martine , Hofman Paul , Merlio Jean-Philippe , McLeer Florin Anne , Galateau-Salle Francoise , Vignaud Jean-Michel , Garcia Stéphane , Thivolet Francoise , Shisheboran-Devouassoux Mojgan , Brevet Marie , Hofman Veronique , Mansuet-Lupo Audrey , Danel Claire 
Published: March 2020

8100 Background: ALK rearrangements occur in nearly 5% of NSCLC and lead to a permanent ALK protein activation, targeted by a small molecule, the crizotinib. To date, FISH (Fluorescent In situ Hybridization) is considered as the gold standard to identify ALK abnormalities, but dual testing and pre-screening by immunohistochemistry have been proposed. Methods: The purpose of the study was to compare immunohistochemistry (IHC) using 5A4 and D5F3 Abs, with FISH and quantitative RT-PCR in a series of 500 surgical specimens, collected within one year from 15 French Thoracic Pathology Departments and INCa genetic platforms. Our study was deliberately enriched in ALK positive cases and clinicopathological data were recorded. Results: Among the 459 cases included to date, 340 were both FISH and IHC ALK negative, and 85 were ALK FISH and IHC positive. Fifteen cases were FISH neg/IHC pos, but with low staining scores; 12 cases were FISH pos/IHC neg, most provided by two centers. Seven cases were non interpretable by FISH, but 5 were ALK IHC positive. Regarding RTqPCR, nearly 50% of ALK positive cases presented a variant 1, 30% a variant 3a/b, and less than 5%, variants 2 or 7; 20%were negative or non interpretable. Discordant cases will be further discussed according to the crizotinib response. ALK positive patients were more frequently women (65 vs 42%) and younger than ALK negative patients (mean age 59 vs 64yrs); 72% were non or light smokers, whereas 75% of ALK negative patients were smokers (mean of 41PY). Histologically, most ALK positive and negative tumors presented a solid or acinar predominant architecture and were P63 negative. However, ALK positive tumors were more frequently TTF1 positive (91 vs 76%). Conclusions: 5A4 or D5F3 immunohistochemistry is a reliable and easy technique for routine diagnosis of ALK abnormalities, while FISH and RT-qPCR still dependent on pre-analytic conditions and technical expertise. However, in case of a suggestive clinical presentation, double testing with FISH remains the safer testing option as false negative IHC cases exist.
Clinical features of patients with lung adenocarcinomas harboring BRAF V600E mutations.
Authors: An Tongtong , Wang Jie , Bai Hua , Wang Zhijie , Zhao Jun , Duan Jianchun , Zhuo Minglei , Wu Meina , Wang Yuyan , Wang Shuhang 
Published: March 2020

8101 Background: To investigate the prevalence, distribution, and prognostic role of activating BRAF mutations in Chinese patients with lung adenocarcinomas (ADCs). Methods: This retrospective study included 192 lung ADCs (97 males 50.5%, 95 females 49.5%). BRAF gene mutations were screened using AmoyDx BRAF V600E mutations detection kit. Mutations of EGFR and KRAS gene were also analyzed. Results: BRAF mutations were present in 8(4.17%) lung ADCs patients. V600E mutations were significantly more prevalent in females (6 of 96; 6.25%) than in males (2 of 97; 2.06%), as indicated by multivariate logistic regression analysis. Other clinocopathologic parameters, including age, smoking history, and tumor stage, were not significantly associated with V600E BRAF mutations. V600E-mutated tumors were not associated with different progression-free and overall survival rates comparing with non V600E-mutated tumors in this study. The frequency of EGFR and KRAS mutations in all patients were 42.7%(82/192) and 8.3%(16/192), respectivelyBRAF and EGFR were concomitantly mutated in three tumors. All tumors with BRAF mutations were found to be negative for KRAS mutations. Conclusions: We report for the first time to our knowledge that V600E BRAF mutation has high concomitant occurrence rate with EGFR mutations in Chinese lung ADCs patients. BRAF mutations were found to be independently associated only with female gender.
SORAVE: Sorafenib and everolimus for treatment of patients with relapsed solid tumors and with KRAS mutated NSCLC—A phase I study.
Authors: Nogova Lucia , Mattonet Christian , Gardizi Masyar , Scheffler Matthias , Bos Marc Christiaan Allardt , Toepelt Karin , Heukamp Lukas Carl , Suleiman Ahmed Abbas , Frechen Sebastian , Soergel Fritz , Fuhr Uwe , Schnell Roland , Katay Ildiko , Behringer Dirk M. , Geist Thomas , Kaminsky Britta , Eichstaedt Martina , Tummes Dirk , Buettner Reinhard , Wolf Jurgen 
Published: March 2020

8112 Background: Dual inhibition of signaling pathways interfering with cell proliferation and angiogenesis may increase anti-tumor efficacy. Sorafenib and mTOR inhibitors showed preliminary activity in KRAS mutated NSCLC. Methods: In the dose escalation part patients with relapsed solid tumors were treated with escalating doses of everolimus from 2.5-10.0 mg daily p.o. in a 14 days run-in phase followed by the combination with a fixed dose of sorafenib 400 mg bid p.o. Extension phase is currently recruiting patients with KRAS mutated NSCLC. The KRAS mutation status was determined by PCR based high resolution melting curve analysis (HRM) on DNA extracted from FFPE material and validated using Sanger sequencing. The HRM has now been replaced by a multiplex PCR. Pharmacokinetic (PK) analyses are performed during run-in and during the combination. Treatment outcome is validated with CT scans on day 57. Results: (I) In the dose escalation part, 19 patients were recruited. The dose limiting toxicity (DLT) was not reached. At everolimus dose level of 10 mg/day, increased rates of grade 3 thrombocytopenia (3 patients), leukocytopenia (2 patients) and anaemia (2 patients) occurred after the DLT interval of 29 days. Based on these observations, the dose level of 7.5 mg/day everolimus in combination with 400 mg sorafenib bid was defined as a maximal tolerated dose. The AUC and Cmax values of everolimus at all dose levels were comparable on days 5 and 14. On day 29, AUC and Cmaxof everolimus showed a 20 - 40% reduction when co-administered with sorafenib. The best treatment outcome was stable disease in 11 patients. Median PFS and OS were 3.7 and 5.5 months, respectively. (II) The extension phase in KRAS mutated NSCLC is currently ongoing. Nine patients have been recruited so far. The CT response at day 57 compared to the baseline of 4 evaluable patients is ranging from -22% to +5% in the sum of the longest diameter of all targeted lesions. Conclusions: Treatment with the combination of 7.5 mg everolimus p.o. daily and 400 mg sorafenib p.o. bid is safe and feasible. Current results of an extension phase in KRAS mutated NSCLC patients show preliminary clinical activity in this patient group with an unfavorable prognosis. Clinical trial information: NCT00933777.
Predicting fitness for chemotherapy in older cancer patients.
Authors: Thomson Damien B. , McCarthy Alexandra , Yates Patsy , Skerman Helen , Walpole Euan Thomas 
Published: March 2020

9516 Background: The Vulnerable Elders Survey-13 (VES-13) is increasingly used to screen for older patients who can proceed to intensive chemotherapy without further comprehensive assessment. This study compared the VES-13 determination of fitness for treatment with the oncologist's assessments of fitness. Methods: Sample: Consecutive series of solid tumour patients ≥65 years (n=175; M=72; range=65-86) from an Australian cancer centre. Patients were screened with the VES-13 before proceeding to usual treatment. Blinded to screening, oncologists concurrently predicted patient fitness for chemotherapy. A sample of 175 can detect, with 90% power, kappa coefficients of agreement between VES-13 & oncologists’ assessments >0.90 ("almost perfect agreement"). Separate backward stepwise logistic regression analyses assessed potential predictors of VES-13 & oncologists’ ratings of fitness. Results: Kappa coefficient for agreement between VES-13 & oncologists’ ratings of fitness was 0.41 (p<0.001). VES-13 & oncologists’ assessments agreed in 71% of ratings. VES-13 sensitivity = 83.3%; specificity = 57%; positive predictive value = 69%; negative predictive value = 75%. Logistic regression modelling indicated that the odds of being vulnerable to chemotherapy (VES-13) increased with increasing depression (OR=1.42; 95% CI: 1.18, 1.71) & decreased with increased functional independence assessed on the Bartel Index (OR=0.82; CI: 0.74, 0.92) & Lawton instrumental activities of daily living (OR=0.44; CI: 0.30, 0.65); RSquare=.65. Similarly, the odds of a patient being vulnerable to chemotherapy, when assessed by physicians, increased with increasing age (OR=1.15; CI: 1.07, 1.23) & depression (OR=1.23; CI: 1.06, 1.43), & decreased with increasing functional independence (OR=0.91; CI: 0.85, 0.98); RSquare=.32. Conclusions: Our data indicate moderate agreement between VES-13 & clinician assessments of patients’ fitness for chemotherapy. Current ‘one-step’ screening processes to determine fitness have limits. Nonetheless, screening tools do have the potential for modification & enhanced predictive properties in cancer care by adding relevant items, thus enabling fit patients to be immediately referred for chemotherapy.
Patients’ perceptions of caregivers’ preference for comfort care at the EOL: Impact on DNR completion.
Authors: Fletcher Kalen Michele , Prigerson Holly Gwen , Maciejewski Paul K 
Published: March 2020

9521 Background: Research has shown that informal caregivers provide substantial psychosocial and material support to advanced cancer patients. Few studies have examined how family caregivers influence patients’ advance care planning. Here we test whether patients’ perceptions of their caregivers’ preference for comfort (vs. life-extending) end-of-life (EOL) care is associated with DNR order completion. We also evaluated whether caregivers’ actual agreement with patients on preference for comfort EOL care was associated with their rates of DNR order completion. Methods: Coping with Cancer II is an NCI –funded, multi-site, prospective cohort study of patients with advanced cancer and their informal family caregivers. Patients are interviewed after receiving restaging scan results and asked if they would prefer a plan of EOL care focused on life-extension or one focused on relieving pain. Patients are also asked what type of EOL care they think their family caregivers would prefer for them and whether or not a DNR order has been completed for them. Caregivers are interviewed separately after patients receive restaging scan results and asked what type of EOL care they would want for the patient. Results: Based on patient data alone (N=72), patients who preferred comfort care at the EOL and who believe that their family caregiver agrees with them on this were significantly more likely than others to report DNR order completion (OR=3.67, p=0.013). Based on data from both patients and caregivers, patients’ perception of agreement with their caregivers on desire for comfort EOL care was more strongly associated with patients’ reports of DNR completion (rs=0.51, p=0.004) than was actual agreement with their caregivers on desire for comfort EOL care (rs=0.36, p=0.045). Conclusions: Patients who prefer comfort care to life-extending care at the EOL, and who think that their caregivers also want them to pursue comfort care, are more likely to have a DNR order completed. Interestingly, patients’ perception of this agreement had a stronger influence on DNR completion than the caregivers’ actual agreement with patients’ preference for comfort EOL care. DNR completion is influenced by patients’ perceptions of family support.
Outcomes of patients ≥ 65 yrs with advanced cancer treated on phase I clinical trials.
Authors: Subbiah Ishwaria Mohan , Wheler Jennifer J. , Hess Kenneth R. , Hong David S. , Fu Siqing , Wolff Robert A. , Kurzrock Razelle , Tsimberidou Apostolia Maria 
Published: March 2020

9544 Background: Older patients with cancer are underrepresented in clinical trials; their disease biology and comorbidities may impact the decision to consider a clinical trial. Here we systematically analyze outcomes of elderly pts treated on phase I clinical trials. Methods: The characteristics, toxicity, survival, and response of pts with advanced cancer treated on phase I clinical trials from 1/04 – 12/09 were studied. Results: Overall,347 of 1,182 pts (29%) were >65 yrs old. The Table lists pt characteristics by treatment regimen. 251 pts received a targeted agent, of which 241 (96%) received an investigational, non-FDA approved drug. Of 347 pts, 3 (1%) had a CR, 15 (4%) a PR, 127 (37%) SD, of which 43 (12%) had SD ≥ 6mos. Of 347 pts, 194 (56%) had >1 drug-related toxicity, of which 89 (26%) had a Grade 3-4 toxicity, most often hematologic; 72% of toxicities on targeted therapies were Grade 1-2. Six pts had a DLT; there was one death (<0.01%) “possibly” attributed to the study drug. Median OS from 1st phase I Clinic visit was 8.8mos (95% CI, 7.8-10.6). Median TTF on 1st phase I trial was 1.9mos (95% CI, 1.8-2.1). Multivariate analyses demonstrated that ECOG PS 2-3 (vs. 01) (p <0.001) and liver mets (vs. no liver mets) (p <0.01) were independent factors predicting shorter TTF and OS. Conclusions: Our results suggest that phase I clinical trials are well tolerated and offer a reasonable therapeutic option for pts > 65 yrs. [Table: see text]
Measures of polypharmacy and chemotherapy toxicity in older adults with cancer.
Authors: Maggiore Ronald John , Feng Tao , Dale William , Gross Cary Philip , Tew William P. , Mohile Supriya Gupta , Owusu Cynthia , Klepin Heidi D. , Lichtman Stuart M. , Gajra Ajeet , McKoy June M , Katheria Vani , Ramani Rupal , Jayani Reena , Brown Jaycen , Hurria Arti 
Published: March 2020

9545 Background: Polypharmacy is common and associated with adverse clinical outcomes in older adults. Potentially inappropriate medication (PIM) use serves as an adjunctive assessment of polypharmacy. The goals of this study in an outpatient population of older adults with cancer (CA) were: 1) to estimate the prevalence of polypharmacy using multiple measures; and 2) to determine the relationship between polypharmacy and chemotherapy (chemo) toxicity. Methods: Medication use was evaluated in 500 patients (pts) age ≥65 years with invasive CA who were starting a new chemo regimen. Polypharmacy was defined by number of daily medications (meds), including non-prescription meds. PIM use was defined by 4 indices: Beers (2003 and 2012 update), Zhan, and HEDIS Drugs to Avoid in the Elderly (DAE) criteria. Prevalence of polypharmacy, PIM, and their association with grade 3-5 chemo toxicity [NCI Common Toxicity Criteria (v. 3.0)] were analyzed using chi square test and unconditional logistic regression. Results: All 500 pts were evaluable [mean age, 73 years (range 65-91); 56% female; 61% stage IV]. The mean number of daily meds was 5 (range 0-23); 38% used ≤3 daily meds, 51% used 4-9 meds, and 11% using ≥10 meds. Using 0-3 daily meds as the referent group, no association was found between daily meds and chemo tox: 4-9 meds, OR 1.34 (95% CI: 0.92-1.97); ≥10, OR 0.82 (95% CI: 0.45-1.49). PIM use was identified in 87 (17%), 147 (29%), 54 (11%), and 69 (13%) patients utilizing the 2003 Beers, 2012 Beers, Zhan, and HEDIS DAE criteria, respectively. There was no association between each PIM use index and chemo toxicity (p>0.10 for all). Conclusions: Polypharmacy and PIM use were common in the geriatric oncology population. Although polypharmacy did not increase the risk of chemotherapy toxicity in this sample, further studies of polypharmacy’s impact on additional outcomes, including non-chemotherapy adverse drug events, in older persons with cancer are warranted.