bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma (GBM) in elderly patients: A randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ).
Authors: Malmstrom A. , Grønberg B. H. , Stupp R. , Marosi C. , Frappaz D. , Schultz H. P. , Abacioglu M. U. , Kinhult S. , Henriksson R. 
Published: February 2017

LBA2002 Background: Despite treatment advances, survival of elderly GBM patients (pts) is usually < 12 months. Hypofractionated RT is advocated in order to shorten treatment time, and chemotherapy has been proposed as an alternative to RT. In a randomized trial we compared two different RT schedules with single-agent TMZ chemotherapy. Methods: Newly diagnosed GBM pts age ≥ 60 years with PS 0-2, were randomized to either standard RT (60 Gy in 2 Gy fractions over 6 weeks) or hypofractionated RT (34 Gy in 3,4 Gy fractions over 2 weeks) or 6 cycles of chemotherapy with TMZ (200 mg/m2 day 1-5 every 28 days). Follow-up including quality of life, symptom checklist, and steroid dosing was completed at 6 weeks, 3 months, and 6 months after start of treatment. The primary study end point was overall survival (OS). Results: A total of 342 pts were included. 291 pts were randomized between the 3 treatment options, 51 pts between hypofractionated RT and TMZ. Median age was 70 years (range 60-88), 59% were male and 72% had undergone tumor resection, the remaining 28% had a diagnostic biopsy only. Performance status was 0-1 for 75% of pts. Survival data are available for 334 pts (98%), with 11 pts (3%) being alive. There was no significant difference in OS between the three treatment arms, with median survival being 8 months for TMZ, 7.5 months for hypofractionated RT and 6 months for 6 weeks RT (p=0.14). Conclusions: Elderly patients with GBM have a short survival. Time-consuming therapy that does not offer longer survival should therefore be avoided. Our study showed no advantage of standard 6 weeks RT compared to hypofractionated RT over 2 weeks or 6 cycles of TMZ chemotherapy. These results indicate that standard RT should no longer be offered to the elderly pt population with GBM. Exclusive TMZ chemotherapy may be an alternative to RT. Subgroup analyses and determination of molecular markers is ongoing. Whether outcome could be improved by concomitant chemoradiotherapy is subject of ongoing clinical trials. [Table: see text]
Phase III trial of induction gemcitabine (G) or paclitaxel (T) plus carboplatin (C) followed by elective T consolidation in advanced ovarian cancer (OC): Final safety and efficacy report.
Authors: Teneriello M. G. , Gordon A. N. , Lim P. , Janicek M. 
Published: February 2017

LBA5008 Background: Safety and efficacy of GC or TC induction followed by elective T consolidation (Tcon) were evaluated. Methods: Patients (pts) with stage IC-IV epithelial OC were randomized to GC: G 1,000 mg/m2 on days 1, 8 plus C AUC=5 on day 1; or TC: T 175 mg/m2 plus C AUC=6 on day 1 for a total of six 21-day cycles. Pts with a complete response (CR) could receive Tcon 135 mg/m2every 28 days for 12 cycles. Non-CR pts received single-agent crossover (CO) therapy (CO-T 175 mg/m2 on day 1 or CO-G 1,000 mg/m2 on days 1, 8) every 21 days until CR or progression of disease (PD). PD or death in 636 pts was required to compare GC and TC with 80% power for progression-free survival (PFS), the primary endpoint. Efficacy results were compared by log-rank test. Results: The trial was stopped in 8/2009 after an ad hoc futility analysis showed low probability of a positive PFS result. Of 919 pts enrolled, 88 pts were excluded (clerical errors); 831 pts were entered; 820 pts had induction; 352 pts had Tcon (GC-Tcon=169, TC-Tcon=183); 155 pts had crossover (CO-T=77, CO-G=78); 313 pts discontinued after induction (GC=165, TC=148). Baseline pt characteristics were balanced across arms. Overall response and adverse events for induction regimens were similar to interim results (Gordon, Clin Ovar Cancer, 2009). For GC and TC, median PFS were 20.0 and 22.2 months; median overall survival (OS) were 43.8 and 57.3 months, respectively. There was no significant difference in PFS (p=0.199) comparing GC and TC. Despite high censorship (GC: 52.8%, TC: 61.4%), OS was greater for TC (p=0.013) compared to GC, but there was no statistical difference after adjusting for significant covariates. For pts with CR, median OS was 65.6 months with Tcon versus 51.4 months without Tcon (p=0.041). Median OS was not reached for TC-Tcon and was 56.1 months for GC-Tcon (p=0.035). For pts not receiving Tcon or receiving either CO-T or CO-G crossover, there was no difference in OS. Conclusions: PFS was similar for GC and TC. Tcon improved OS. However, OS analysis was limited by study design and high censorship. GC does not offer an advantage over standard of care TC for first-line chemotherapy in advanced OC. No significant financial relationships to disclose.
Phase III trial (EORTC 10994/BIG 00-01) assessing the value of p53 using a functional assay to predict sensitivity to a taxane versus nontaxane primary chemotherapy in breast cancer: Final analysis.
Authors: Bonnefoi H. R. , Bogaerts J. , Piccart M. , Mauriac L. , Fumoleau P. , Jassem J. , Becette V. , Cameron D. A. , Bergh J. , Iggo R. ,   on behalf of the EORTC, SweBCG, SAKK, and ACCOG Investigators
Published: February 2017

LBA503 Background: Predictive markers of response to chemotherapy are lacking. Preclinical data suggest that p53 mutated tumors are resistant to anthracyclines and sensitive to taxanes. However, clinical data are contradictory. Using a functional yeast assay to detect biologically important mutations, this study tested the hypothesis that docetaxel confers a greater advantage over anthracyclines in p53 mutated tumors (mut) than p53 wild type (wt). Methods: Patients (pts) with locally advanced/inflammatory or large operable tumors were randomized to either a standard anthracycline regimen (arm A) or a taxane-based treatment (arm B). In arm A pts received 6 cycles of FEC 100, or tailored FEC + G-CSF (Swedish cohort). In arm B docetaxel (T) 100mg/m2 was given for 3 cycles, followed by 3 cycles of epirubicin 90mg/m2and T 75mg/m2 q3 weeks (T-ET). After chemotherapy, pts underwent surgery followed by radiotherapy. Endocrine therapy and/or trastuzumab were given according to each center's policy. Fresh frozen tumor biopsies were mandatory before starting chemotherapy: frozen sections were examined centrally and the p53 test was done when the invasive tumor cell content was > 20%. cDNA derived from tumor-extracted RNA was transfected into yeast (Flaman et al. PNAS 1995): tumors were deemed p53 wt when there were < 20% red colonies (background) and p53 mut > 20%. The three co-primary comparisons for the endpoint of progression-free survival (PFS) were between arms A and B in p53 mut, p53 wt, and the entire trial population, each at a p=0.02. The sample size gave sufficient power for an interaction test for outcomes between p53 mut and wt at p<0.05. Results: From April 2001 to November 2006, 1,856 patients were included. A total of 386 pts (21%) were ineligible (including 292 pts with <20% tumor cells and 67 without sample). No unexpected toxicity was observed. At the time of analysis 675 events were registered after a median follow-up time of 57 months. The results are summarized below. Conclusions: p53 is not a predictive factor of response or resistance to taxanes, although it is, as expected, prognostic (<0.001). PFS is not statistically significantly different between FEC and T-ET arms at the 2% cutoff level. [Table: see text] [Table: see text]
A randomized phase II trial of mapatumumab, a TRAIL-R1 agonist monoclonal antibody, in combination with carboplatin and paclitaxel in patients with advanced NSCLC.
Authors: Von Pawel J. , Harvey J. H. , Spigel D. R. , Dediu M. , Reck M. , Cebotaru C. L. , Kumm E. , Gallant G. , Fox N. , Camidge D. R. 
Published: February 2017

LBA7501 Background: Mapatumumab, a fully human agonist monoclonal antibody, targets and activates the death receptor TRAIL-R1. We conducted this randomized, controlled phase II trial to evaluate mapatumumab in combination with carboplatin and paclitaxel as first-line therapy in advanced non-small call lung cancer (NSCLC). Methods: Patients were required to have histologically or cytologically confirmed Stage IIIB or IV advanced primary NSCLC with measurable disease by RECIST. Patients were randomly assigned to Arm A, paclitaxel 200 mg/m2 + carboplatin AUC 6.0 (PC); Arm B, PC + mapatumumab 10 mg/kg; or Arm C, PC + mapatumumab 30 mg/kg. Cycles were repeated every 21 days; patients completed up to 6 cycles in the absence of evidence of disease progression or unacceptable toxicity. Patients in Arms B and C could receive additional cycles of mapatumumab in the absence of disease progression. The co-primary endpoints were response rate (RR; complete response + partial response) and progression-free survival (PFS). Images were read by independent radiologists blinded to treatment group assignment, as well as locally. Results: 111 patients were enrolled at 22 sites in 4 countries. Addition of mapatumumab to PC did not improve RR or PFS. RR and PFS, based on the independent read, and overall survival results are summarized below. The results based on local reading also showed no benefit from the addition of mapatumumab to PC. Adverse events were generally balanced across treatment groups; there was no evidence that mapatumumab exacerbated toxicities associated with PC. Conclusions: The results do not support further evaluation of mapatumumab in combination with PC in patients with advanced NSCLC. Additional trials of mapatumumab in other indications are ongoing. [Table: see text] [Table: see text]
Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: First results of the German CAO/ARO/AIO-04 randomized phase III trial.
Authors: Roedel C. , Becker H. , Fietkau R. , Graeven U. , Hohenberger W. , Hothorn T. , Lang-Welzenbach M. , Liersch T. , Staib L. , Christiansen H. , Wittekind C. , Sauer R. ,   German Rectal Cancer Study Group
Published: February 2017

LBA3505 Background: The German CAO/ARO/AIO-94 trial established preoperative chemoradiotherapy (CRT), surgery, and postoperative chemotherapy with 5-FU as standard treatment for locally advanced rectal cancer. With this approach local relapse rates are below 10%. The development of distant metastasis is the predominant mode of failure. Integrating more effective systemic treatment into combined modality therapy was the goal of CAO/ARO/AIO-04. Methods: Between 7/2006-2/2010, patients with rectal cancer within 12 cm from the anal verge and clinical evidence of perirectal fat or lymph node involvement were randomly assigned to receive preoperative CRT, surgery, and adjuvant chemotherapy with 5-FU according to CAO/ARO/AIO-94 (arm 1), or preoperative CRT (50.4 Gy in 28 fractions) with 5-FU (250 mg/m2/days 1-14 and 22-35) and oxaliplatin (50 mg/m2/days 1, 8, 22, 29), surgery, and 8 cycles of adjuvant chemotherapy according to modified FOLFOX6 regimen (arm 2). Disease-free survival was the primary endpoint. We present early secondary endpoints, including acute toxicity, treatment compliance, and pCR-rates. Results: 637 patients were randomly assigned to arm 1 and 628 to arm 2. Full dose preoperative RT and full dose concurrent chemotherapy was delivered in 97% and 74% of patients in both arms, respectively. Preoperative grade 3/4 toxicity occurred in 21.6% in arm 1 and in 22.9% in arm 2. The R0-resection rate was 95.4% in both arms, and abdominoperineal resections were limited to 11.9% and 12.2% in arms 1 and 2, respectively. Overall postoperative complications were not different between both arms (21.0% and 21.9%). The pCR rate (ypT0N0) was 13.1% in arm 1 and 17.6% in arm 2 (p = 0.033, Cochran-Mantel-Haenszel Chi-Squared Test without continuity correction for conditional independence of pCR rate in the two treatment arms in each stratum). Conclusions: Inclusion of oxaliplatin to 5-FU based CRT was well tolerated and associated with increased pCR-rates compared with 5-FU-CRT alone. Longer follow-up is necessary to evaluate the primary endpoint, disease-free survival.
Phase III randomized, open-label, multicenter trial (BRIM3) comparing BRAF inhibitor vemurafenib with dacarbazine (DTIC) in patients with V600EBRAF-mutated melanoma.
Authors: Chapman P. B. , Hauschild A. , Robert C. , Larkin J. M. G. , Haanen J. B. A. G. , Ribas A. , Hogg D. , O'Day S. , Ascierto P. A. , Testori A. , Lorigan P. , Dummer R. , Sosman J. A. , Garbe C. , Lee R. J. , Nolop K. B. , Nelson B. , Hou J. , Flaherty K. T. , McArthur G. A. 
Published: February 2017

LBA4 Background: About 50% of melanomas have an activating V600EBRAF mutation which led to the hypothesis that inhibition of the mutated BRAF kinase may be of clinical benefit. Phase I and II trials with vemurafenib (previously PLX4032/RO5185426), an orally available inhibitor of oncogenic BRAF kinase, showed response rates (RR; CR+PR) >50% in V600EBRAF- mutated melanoma patients (pts). We conducted a phase III trial to determine if vemurafenib improved overall survival (OS) and progression-free survival (PFS) in melanoma pts with V600EBRAF mutation. Methods: Pts with previously untreated, unresectable stage IIIC or stage IV melanoma that tested positive for V600EBRAF mutation by the cobas 4800 BRAF V600 Mutation Test were randomized (1:1) to vemurafenib (960 mg po bid) or DTIC (1,000 mg/m2, IV, q3w). Randomization was stratified by PS, stage, LDH, and geographic region. Pts were assessed for tumor responses after weeks 6, 12, and then q9 weeks. Co-primary endpoints were OS and PFS on the intent-to-treat population; secondary endpoints included RR, response duration, and safety. Final analysis was planned at 196 deaths. Results: 675 pts were enrolled at 103 centers worldwide between Jan and Dec 2010. Treatment cohorts were well-balanced. At the pre-planned interim analysis (50% of deaths needed for final analysis), the hazard ratios for OS and PFS were 0.37 (95% CI 0.26 to 0.55; p<0.0001) and 0.26 (95% CI 0.20 to 0.33; p<0.0001), respectively, both in favor of vemurafenib. The confirmed RR was 48.4% and 5.5% to vemurafenib and DTIC, respectively, among the 65% of pts evaluable for RR to date. Benefit in OS, PFS, and RR was seen in all subgroups examined. Due to these data, the DTIC cohort has been allowed to cross over to vemurafenib. At the time of data analysis, 66% of vemurafenib pts and 25% DTIC pts were still on treatment. The most common toxicities of vemurafenib were: diarrhea, rash, alopecia, photosensitivity, fatigue, arthralgia, and keratoacanthoma/skin squamous cell carcinoma. Conclusions: Vemurafenib is associated with significantly improved OS and PFS compared to DTIC in pts with previously untreated, V600EBRAF-mutated metastatic melanoma.
Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients with unresectable stage III or IV melanoma.
Authors: Wolchok J. D. , Thomas L. , Bondarenko I. N. , O'Day S. , Weber J. S. , Garbe C. , Francis S. , Ibrahim R. A. , Hoos A. , Robert C. 
Published: February 2017

LBA5 Background: IPI monotherapy (3mg/kg) improved overall survival (OS) in a phase III study of previously treated, unresectable or metastatic melanoma. Current study in 1st line metastatic melanoma evaluates combination of DTIC (a global standard of care) plus IPI. Methods: In this double-blind phase 3 study, patients (pts) with metastatic melanoma, ECOG PS 0/1, and no prior therapy for advanced disease, were randomized 1:1 to IPI (10 mg/kg) + DTIC (850 mg/m2) or placebo + DTIC (850 mg/m2) at Wks 1, 4, 7, 10 followed by DTIC q3 wks through Wk 22 (induction). Eligible pts received IPI or placebo q12 wks as maintenance. Primary endpoint was OS; 2-sided log-rank test was performed, stratified by baseline M stage and ECOG PS. Results: Of 502 pts, 56% had M1c disease, 40% elevated LDH, and 26% adjuvant therapy. 37% in IPI + DTIC and 65% in DTIC alone arms received 4 induction doses. A significant improvement in OS (HR=0.72; P=0.0009) and higher estimated 1, 2 and 3 yr survival rates were seen with IPI + DTIC (Table). 56% in IPI +DTIC (n=247) and 27% in DTIC alone (n=251) arms had grade 3/4 adverse events (AEs, regardless of attribution), including: elevated ALT (22% vs 1%); diarrhea (4% vs 0%); rash (1% vs 0%). No intestinal perforations or hypophysitis were noted. There were no drug-related deaths in IPI + DTIC and one in DTIC alone arm [gastrointestinal (GI) hemorrhage]. Conclusions: IPI (10mg/kg) + DTIC significantly improved OS in 1st line metastatic melanoma vs DTIC alone; durable survival and objective responses were noted in some pts after follow-up for up to 4yrs. Type of AEs was consistent with prior IPI studies; however, frequencies of some AEs differed with a higher transaminitis and lower diarrhea/colitis/ GI perforation rates than expected. No drug-related deaths were noted in IPI arm. OS benefit of IPI is confirmed in treatment-naive metastatic melanoma. [Table: see text]
An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: Scagliotti G. , Vynnychenko I. , Ichinose Y. , Park K. , Kubota K. , Blackhall F. H. , Pirker R. , Galiulin R. , Ciuleanu T. , Sydorenko O. , Dediu M. , Papai-Szekely Z. , Martinez Banaclocha N. , McCoy S. , Yao B. , Hei Y. J. , Spigel D. R. 
Published: February 2017

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]
The ultra-low molecular weight heparin (ULMWH) semuloparin for prevention of venous thromboembolism (VTE) in patients with cancer receiving chemotherapy: SAVE ONCO study.
Authors: Agnelli G. , George D. J. , Fisher W. , Kakkar A. K. , Lassen M. R. , Mismetti P. , Mouret P. , Chaudhari U. , Turpie A. G. G. 
Published: February 2017

LBA9014 Background: Patients receiving chemotherapy for cancer are at increased risk for VTE; large randomized controlled trials (RCT) are needed to demonstrate benefit of antithrombotic prophylaxis. Semuloparin is a novel ULMWH with high anti-factor Xa and residual anti-factor IIa activities. We performed a multinational RCT to assess the efficacy and safety of semuloparin for VTE prevention in cancer patients receiving chemotherapy (SAVE-ONCO). Methods: This was a double-blind study in patients with metastatic or locally advanced cancer of lung, colon-rectum, stomach, ovary, pancreas, or bladder, initiating a new chemotherapy course. Patients were randomized to receive subcutaneous semuloparin, 20 mg od, or placebo, until change of chemotherapy. The primary efficacy outcome was the composite of any symptomatic deep vein thrombosis (DVT), non fatal pulmonary embolism (PE) and VTE-related death. Clinically relevant bleeding was the main safety outcome. Outcomes were adjudicated by an independent Committee. Results: Of 3,212 randomized patients, 68% had metastatic cancer; the majority had lung (37%) or colon-rectum (29%) cancer. Median treatment duration was ~3.5 months. Twenty of the 1,608 patients treated with semuloparin (1.2%) and 55 of the 1,604 patients treated with placebo (3.4%) had a thromboembolic event, representing a 64% risk reduction in such event rate (hazard ratio [HR]=0.36, 95% confidence interval [CI] 0.21–0.60, p<0.0001, intent-to-treat analysis). Treatment effect was consistent for DVT and PE, with a 59% risk reduction in PE rate (odds ratio 0.41, 95%CI 0.19–0.85). No heterogeneity in the benefit was observed for cancer type or stage. Nineteen of 1,589 patients (1.2%) in the semuloparin and 18 of the 1,583 patients (1.1%) in the placebo group had a major bleeding (HR=1.05, 95%CI 0.55 to 1.99). The rate of clinically relevant bleeding was 2.8% with semuloparin vs 2.0% with placebo (HR=1.40, 95%CI 0.89–2.21). Conclusions: We have demonstrated the benefit of thromboprophylaxis with semuloparin in patients receiving chemotherapy without increase in major bleeding. Such patients should be considered for thromboprophylaxis.