bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abiraterone + prednisone (Abi) +/- veliparib (Vel) for patients (pts) with metastatic castration-resistant prostate cancer (CRPC): NCI 9012 updated clinical and genomics data.
Authors: Hussain Maha , Daignault Stephanie , Twardowski Przemyslaw , Albany Costantine , Stein Mark N. , Kunju Lakshmi Priya , Robinson Dan R. , Cooney Kathleen A. , Montgomery Robert B. , Antonarakis Emmanuel S. , Shevrin Daniel H. , Corn Paul Gettys , Whang Young E. , Smith David C. , Caram Megan Veresh , Tomlins Scott A. , Knudsen Karen E. , Stadler Walter Michael , Feng Felix Yi-Chung , Chinnaiyan Arul M. 
Published: September 2018

5001 Background: In preclinical CRPC models, PARP1 inhibition synergizes with AR targeted therapy, especially in ETS fusion-positive tumors. We hypothesized: 1. Co-targeting PARP-1 + AR is superior to AR inhibition and 2. ETS +ve predicts response. Methods: Pts had metastatic (mets) disease biopsy (bx), stratified by IHC-ETS status and randomized to Abi (Arm A) or Abi + Vel (Arm B). Primary endpoint: PSA response rate (RR > = 50% decline). Secondary endpoints: safety, objective RR (ORR), progression free survival (PFS), and molecular analysis including if DNA repair gene deficiency (DRD: BRCA 1, BRCA 2, ATM, FANCA, PALB2, RAD51B, RAD51C) predicts response. 148 pts stratified by IHC-ETS status were randomized to detect a 20% PSA RR improvement assuming a 5% 1-sided type I error and 80% power. An elastic net multivariable Cox model was used to analyze PFS. Mets bx underwent targeted exon sequencing and capture transcriptome analysis. Results: 72 pts were randomly assigned to Arm A and 76 to Arm B. PSA RR: Arm A 63.9%, Arm B 72.4% (p = 0.27). ORR: Arm A 45%, Arm B 52.2%, p = 0.51. Median PFS: Arm A 10.1 months (m), Arm B 11.3 m, p = 0.95. More Arm-B pts were on therapy for 12+ (45% vs 38%) and 18+ cycles (22% vs 17%). ETS status had no impact. Mets tissue sequencing (N = 80): 42 pts (53%) were ETS +ve, 19 (25%) had DRD, 47 (59%) had AR amplification/copy gain, 32 (40%) had PTEN mutation (mut), 33 (41%) had TP53 mut, 37 (46%) had PIK3CA activation (a) and 12 (15%) had WNT-a. Irrespective of arm pts with DRD had a higher PSA and ORR ( > = 87%) vs wild type (58%, 39%; p = 0.013, p = 0.002, respectively), higher PSA decline rate of > = 90% (74% vs 26%, p = 0.0004) and longer median PFS (95% CI): DRD 16.6 m (11 - NR) vs wild type: 8 m (5.4 – 13.3); p = 0.02. PFS was longer in pts with normal PTEN (13.5 vs 6.2 m, p = 0.02), TP53 (13.3 vs 7.8 m, p = 0.04) and PIK3CA (10.3 vs 8.3 m, p = 0.03). Controlling for clinical factors, DRD, PTEN, TP53 and PIK3CA are associated with PFS in this order of importance. Conclusions: There was a modest trend in favor of Abi + Vel but no difference by ETS. Pts with DRD, normal PTEN,TP53 and PIK3CA had better PFS raising new hypotheses regarding the importance of integrating molecular analysis in therapeutic trials. Clinical trial information: NCT01576172.
The benefit of combining docetaxel to androgen deprivation therapy in localized and metastatic castration-sensitive prostate cancer as predicted by ERG status: An analysis of two GETUG phase III trials.
Authors: Rajpar Shanna , Carmel Alexandra , Merabet Zahira , Vielh Philippe , Foulon StÃ©phanie , Lesaunier Francois , Delva Remy , Rolland Frederic , Priou Frank , Ferrero Jean-Marc , Houede Nadine , Mourey Loic , Theodore Christine , Krakowski Ivan , Faivre Laura , Habibian Muriel , Culine Stephane , Chauchereau Anne , Gravis Gwenaelle , Fizazi Karim 
Published: September 2018

5012 Background: Combining docetaxel to androgen deprivation therapy (ADT) improves survival in metastatic castration-sensitive prostate cancer (CSPC) (Vale C, Lancet Oncol 2016; 17: 243-56) and it also improves relapse-free survival (RFS) in high-risk localized CSPC (Fizazi K, Lancet Oncol 2015; 16: 787-94). However it is unlikely that all patients (pts) derive a benefit from docetaxel treatment and identifying predictive biomarkers remains a major unmet need. A subset of prostate cancers contains TMPRSS2-ERG gene fusions leading to ERG overexpression. Methods: Pre-treatment prostate core biopsies were collected from 255/413 pts and 79/385 pts enrolled respectively in the GETUG 12 and GETUG 15 (Gravis G, Eur Urol 2016; 70: 256-62) phase 3 trials testing early docetaxel in high-risk localized and metastatic CSPC. ERG, PTEN, Ki67 and Rb expression was assessed using immunohistochemistry. RFS curves were compared using the Logrank test. Results: The median age was 63 years (46-77) and 62 years (49-76) in GETUG 12 and GETUG 15. ERG staining was positive in 88/191 (46%) and 33/79 (42%) pts with available tissue, respectively. In GETUG 12, docetaxel-based chemotherapy was associated with improved RFS in pts with ERG+ expression (HR = 0.55 [0.29-1.03]; 6-year RFS : 80% ADT+docetaxel vs 68% ADT alone), but not in pts with ERG- (HR = 1.10 [0.66-1.85]; 6-year RFS 55% ADT+docetaxel vs 60% ADT alone), interaction test: p = 0.02. Similar findings were observed in GETUG 15, which was used as a validation set: the median RFS was 10.7 (6.5-14.3) and 18.8 (9.8-41) months in pts with ERG+ cancers receiving ADT alone and ADT+docetaxel, and 10.6 (4.8-25.3) and 13.2 (9.4-24) months in pts with ERG- cancers. In contrast, no difference in patient outcome by docetaxel treatment was observed by PTEN, Ki67 and Rb expression. Conclusions: Docetaxel-related benefit in men with CSPC is predicted by ERG expression. This biomarker may help better select pts for docetaxel treatment.
SOLE (Study of Letrozole Extension): A phase III randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC).
Authors: Colleoni Marco , Luo Weixiu , Karlsson Per , Chirgwin Jacqueline H. , Aebi Stefan Paul , Jerusalem Guy Heinrich Maria , Neven Patrick , Hitre Erika , Graas Marie-Pascale , Simoncini Edda , Kamby Claus , Thompson Alastair Mark , Loibl Sibylle , Gavilá Joaquín , Kuroi Katsumasa , Gnant Michael , Rabaglio-Poretti Manuela , Regan Meredith M. , Coates Alan S. , Goldhirsch Aron 
Published: September 2018

503 Background: In animal models of hormone receptor positive (HR+) breast cancer, acquired resistance to continued letrozole was shown to be reversed by estrogen-induced apoptosis. Sensitization to reintroduction of estrogen withdrawal by letrozole was hypothesized to improve treatment outcome. SOLE tested the hypothesis that 3 mos treatment-free intervals during extended adjuvant therapy will improve disease-free survival (DFS). Methods: SOLE enrolled 4884 postmenopausal women with HR+ lymph node-positive BC who had completed 4-6 yrs of adjuvant endocrine therapy (19% SERM, 43% AI, 38% both; stratification factor). Pts were randomly assigned to an additional 5 yrs continuous letrozole (2.5 mg daily; n = 2441) vs 5 yrs intermittent letrozole (taken for the first 9 mos of yrs 1-4, and 12 mos in yr 5; n = 2443). The primary endpoint was DFS (randomization until invasive local, regional, distant recurrence or contralateral BC; 2nd malignancy; death). Final analysis was at 665 DFS events, after 2 interim analyses. SOLE required 4800 pts for 80% power to detect a 20% DFS hazard reduction with 2-sided α = 0.05 using a stratified log rank test. Analysis is by intention-to-treat. Results: At 60 mos median follow-up, 5 yr DFS from randomization was 85.8% vs 87.5% for patients assigned intermittent vs continuous letrozole (HR = 1.08; 95% CI 0.93-1.26; P = 0.31). Similar outcome was observed for breast cancer-free interval (HR = 0.98; 95% CI 0.81-1.19), distant recurrence-free interval (HR = 0.88; 95% CI 0.71-1.09), and overall survival (HR = 0.85; 95% CI 0.68-1.07). AEs of grade > 3 were reported for 43.5% vs 41.6% of pts assigned intermittent vs continuous letrozole. Overall 24% pts discontinued letrozole early in both groups. Conclusions: Among postmenopausal women with HR+ BC, extended intermittent letrozole did not improve DFS vs continuous letrozole. The similar observed outcomes and incidence of AEs provides clinically relevant information on the intermittent administration of extended letrozole for patients who could benefit from temporary treatment breaks. Clinical trial information: NCT00553410.
Patient (pt) characteristics and treatment patterns in the radium (Ra)-223 REASSURE observational study.
Authors: Higano Celestia S. , Zimberg Shawn H. , Dizdarevic Sabina , Harshman Lauren Christine , Logue John , Baldari Sergio , Richardson Timothy , Bottomley David M. , Schostak Martin , Tombal Bertrand F. , Sade Juan Pablo , Miller Kurt , Logothetis Christopher , Bellmunt Joaquim , Smith Matthew Raymond , Saad Fred , Muenz-Wollny Renate , De Sanctis Yoriko , Sartor A. Oliver , Sternberg Cora N. 
Published: September 2018

5042 Background: Ra-223, a targeted alpha therapy, prolonged survival with good safety in metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 ALSYMPCA trial. REASSURE will evaluate Ra-223 short- and long-term safety in routine clinical practice settings. This is the first planned interim analysis (median 7 mo observation). Methods: This global, prospective, single-arm, observational study enrolled pts with mCRPC with bone metastases (mets) for whom Ra-223 therapy was planned. Follow-up will continue up to 7 years after last Ra-223 dose. Results: 1106 pts (437 N. America, 665 Europe, 4 not recorded) enrolled from 2 Sep 2014 to 22 Sep 2016. Baseline data are available from 583 pts receiving 1st- (1L), 2nd- (2L), or ≥3rd-line (≥3L) Ra-223 for mCRPC(Table). The majority of pts (n=369, 63%) completed 5–6 doses (1L, 70%; 2L, 64%; ≥3L, 49%); median 6 doses (1L,6; 2L, 6; ≥3L, 4). Treatment-emergent drug-related AEs occurred in 215 pts (37%). Post-treatment grade 3/4 thrombocytopenia occurred in 14 pts (2.4%) and anemia in 45 (7.7%). Conclusions: In routine clinical practice, Ra-223 was associated with no short-term safety concerns and appeared to be used in pts with less advanced mCRPC than in ALSYMPCA. The majority of pts on 1L/2L Ra-223 therapy received 5–6 doses. Ra-223 was often used with abiraterone or enzalutamide, but not chemotherapy. The next interim analysis in 2019 will report long-term safety and outcomes on all pts. Clinical trial information: NCT02141438. [Table: see text]
Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): Results from I-SPY 2.
Authors: Nanda Rita , Liu Minetta C. , Yau Christina , Asare Smita , Hylton Nola , Veer Laura Van't , Perlmutter Jane , Wallace Anne M. , Chien Amy Jo , Forero-Torres Andres , Ellis Erin , Han Heather , Sanders Clark Amy , Albain Kathy S. , Caroline Boughey Judy , Elias Anthony D. , Berry Donald A. , Yee Douglas , DeMichele Angela , Esserman Laura 
Published: September 2018

506 Background: Pembro is an anti-PD-1 antibody with single agent activity in HER2– metastatic BC. I-SPY 2 is a multicenter, phase 2 platform trial which evaluates novel neoadjuvant therapies; the primary endpoint is pathological complete response (pCR, ypT0/Tis ypN0). We report current efficacy results, with final results at ASCO. Methods: Patients (pts) with invasive BC ≥2.5 cm by exam or ≥2 cm by imaging are assigned weekly paclitaxel x 12 (control) +/- an experimental agent, followed by doxorubicin/cyclophosphamide x 4. Combinations of hormone-receptor (HR), HER2, & MammaPrint (MP) status define the 8 signatures studied. MP low HR+ BC is excluded. Adaptive randomization is based on each arm’s Bayesian probability of superiority over control. Graduation by signature is based on an arm’s Bayesian predictive probability of a successful 1:1 randomized phase 3 trial with a pCR endpoint. We provide raw & Bayesian estimated pCR rates adjusted for covariates, time effects over the course of the trial, & serial MRI modeling for pts not yet assessed for pCR surgically. Results: 69 pts were randomized to pembro (HER2- subsets only) from Dec 2015 until it graduated in Nov 2016. 46 pts have undergone surgery (table); the other 23 have on-therapy MRI assessments. In 29 HR–/HER2– (TNBC) pts, pembro increased raw & estimated pCR rates by >50% & 40%, respectively; in 40 HR+/HER– pts, it did so by 13% and 21%. 5 pts had immune-related grade 3 adverse events (AEs); 1 hypophysitis & 4 adrenal insufficiency. 4 pts presented after completion of AC (149-179 d after starting pembro); 1 presented prior to AC (37 d after starting pembro). 7 pts had grade 1-2 thyroid abnormalities. Conclusion: Pembro added to standard therapy improved pCR rates in all HER2- BCs that meet I-SPY 2 eligibility, especially in TNBC. Immune-mediated AEs were observed; pt follow up is ongoing. Clinical trial information: NCT01042379. [Table: see text]
Changes in CTC burden and prevalence of specific CTC subtypes in mCRPC patients (pts) receiving alpharadin (Ra-223) as single agent or in combination with other therapuetics (Tx).
Authors: Dittamore Ryan Vance , Jendrisak Adam , Schreiber Nicole A. , McLaughlin Brigit , Graf Ryon , Rodriguez Angel , Fleisher Martin , Lee Jerry , Kelvin James , Wang Yipeng , Landers Mark Andrew , Scher Howard I. 
Published: September 2018

5076 Background: Ra-223 prolongs life in mCRPC pts with symptomatic osseous metastasis with inconsistent effects on PSA. Survival times are prolonged further when combined with Abi/Enza. Data from preclinical studies suggest that Ra-223 may sensitize tumors to DDR agents and/or biologic therapies. But predictive biomarkers of benefit to each or both combinationso are lacking. We studied CTC counts and the prevelance of specific CTC subtypes in patients before and following Ra-223 therapy, both as a single agent and in combination, to identify biomarkers of sensitivity and treatement efficacy, and effects of Ra-223 on tumor biology. Methods: Pre and ~4 week post RA-223 therapy blood samples were collected from 35 pts (2 samples each) given as a single agent (n = 20 pts) or in combination with other therapies (n = 15 pts, 9 w/ Enza, 5 w/ Abi, 1 w/ Taxane). Samples were processed and CTCs analyzed using the Epic Sciences platform. Total CTC count and the prevalence of specific CTC phenotypes present pre and post Rx were identified utilizing high content digital pathology and associated with therapy type and post-treatment change. Results: CTC declines were observed in 55% (11/20) and 60% (9/15) of pts treated with single agent and combination respectively. In Ra-223 alone pts, a novel CTC subtype (high N/C ratio, high nuclear area) was identified at baseline 11/20 samples (med = 33% of CTCs). Which was no longer detected in 10 (90%) of the pts treated. This contrasts with a second novel CTC subtype present at baseline in 4 pts (med CTC = 9%) that increased to 9 cases (med CTC = 18%) at follow-up. Conclusions: A subset of pts demonstrate post-therapy CTC declines following Ra-223 alone or in combination. A novel CTC subtype resolved by RA-223 in conjunction with total CTC kinetics may indicate pt benefit from Ra-223. A novel emergent CTC subtype has also been identified in pts already receiving Ra-223. Single CTC sequencing and protein analysys of these CTC subtypes are ongoing, and may help describe tumor evolution and sensitization to novel therapuetics.
A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto).
Authors: Schneeweiss Andreas , Moebus Volker , Tesch Hans , Hanusch Claus , Denkert Carsten , Luebbe Kristina , Huober Jens Bodo , Klare Peter , Kummel Sherko , Untch Michael , Kast Karin , Jackisch Christian , Thomalla Jörg , Ingold Heppner Barbara , Blohmer Jens U. , Rezai Mahdi , Frank Matthias , Nekljudova Valentina , Von Minckwitz Gunter , Loibl Sibylle 
Published: September 2018

518 Background: The sequential use of intense does-dense (idd) epirubicin, paclitaxel, cyclophosphamide (EPC) and weekly paclitaxel/liposomal doxorubicin (+/- carboplatin (Cb) in triple negative breast cancer (TNBC) (PM(Cb)) are considered highly efficient regimens for high-risk early stage breast cancer (BC). Methods: GeparOcto (NCT02125344) patients (pts) received 18 weeks (wks) either EPC (3x E 150mg/m² q2w followed by 3x P225 mg/m² q2w followed by 3x C 2000mg/m² q2) or PM(Cb) (12x P 80mg/m² plus M 20 mg/m² q1w, plus Cb AUC 1.5 q1w in TNBC). For HER2+ BC trastuzumab 6 (8) mg/kg q3w and pertuzumab 420 (840) mg q3w cycles were given concomitantly with P and C. Pts with histologically confirmed, cT1c - cT4a-d BC and central receptor assessment were included. Pts with HER2+ or TNBC were eligible irrespective of nodal status, luminal B-like tumours only if pN+. Primary objective compared pathologic complete response (pCR) rates (ypT0/is ypN0). Sample size calculations assumed a pCR rate of 50% for EPC and 60% for PM(Cb), requiring 950 pts to show superiority of PM(Cb). Secondary objectives compared pCR rates within the stratified subgroups (BC subtype, HER2+ vs HER2- HR+ vs HER2- HR-), amongst others. Results: 961 pts were recruited between 12/2014 and 05/2016, 945 started treatment. Median age was 48 years, 4% T3, 2% T4d, 46% N+, 82% ductal invasive, 66% G3 tumors; 40% were HER2+, 43% TNBC. 347 pts reported SAEs (176 EPC/171 PM(Cb)) and 2 pts died. 35 pneumonias (2 EPC vs 33 PM(Cb)) and 18 pneumonitis (3 EPC vs 15 PM(Cb)) were reported. 16.4% pts with EPC and 33.8% with PM(Cb) discontinued treatment (p<0.001), mainly due to AEs (47 EPC vs 113 PM(Cb)). Mean treatment duration was 17 wks with EPC and 16 wks with PM(Cb). pCR rate was 48.3% with EPC and 47.6% with PM(Cb)(OR 0.97 (95%CI 0.75-1.25), p=0.876). pCR rate in TNBC was 48.5% with EPC and 51.7% with PM(Cb); in HER2+ 62.0% vs 57.4% and in Luminal B 14.1% vs 14.6%. Conclusions: In high-risk early stage breast cancer pts pCR rates of idd EPC compared to weekly PM(Cb) were not significantly different. PM(Cb) appeared to be less feasible. Clinical trial information: NCT02125344.
Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in patients (pts) with early stage triple-negative breast cancer (TNBC).
Authors: Geyer Charles E. , O'Shaughnessy Joyce , Untch Michael , Sikov William , Rugo Hope S. , McKee Mark D. , Huober Jens Bodo , Golshan Mehra , Giranda Vincent L. , Von Minckwitz Gunter , Maag David , Sullivan Danielle Marie , Wolmark Norman , McIntyre Kristi , Ponce Lorenzo Jose Juan , Metzger Filho Otto , Rastogi Priya , Symmans William Fraser , Liu Xuan , Loibl Sibylle 
Published: September 2018

520 Background: Clinical studies suggest that TNBC is sensitive to DNA-damaging agents, including Cb. V is a potent PARP inhibitor that may enhance the antitumor activity of such agents. We present primary response data from a phase 3 randomized, placebo-controlled study (NCT02032277) evaluating the addition of V + Cb or Cb to neoadjuvant paclitaxel (P) followed by doxorubicin + cyclophosphamide (AC). Methods: Pts with histologically confirmed, invasive TNBC (T2–T4 N0–2 or T1 N1–2) amenable to surgical resection were randomized 2:1:1 to (Arm A) P 80 mg/m2 weekly + Cb AUC 6 mg/mL/min q3 weeks + V 50 mg PO BID; (Arm B) P + Cb + PO placebo; or (Arm C) P + IV placebo + PO placebo, for 12 weeks followed by AC (60 mg/m2 or 600 mg/m2 q2 or 3 weeks) × 4. Primary endpoint was pathologic complete response (pCR) in breast and nodes with > 80% power at 2-sided α of 0.05 using pair-wise comparisons for A vs B and A vs C to detect significant treatment effects using Χ2 test; secondary endpoint was rate of conversion to eligibility for breast conservation surgery (BCS). Adverse events (AEs) were assessed with NCI CTCAE V4.0. Results: Six hundred thirty-four pts (median age 50 years; range 22–79) were randomized to Arms A (n = 316), B (n = 160), or C (n = 158). Baseline characteristics were well balanced. No pCR difference was observed between Arms A and B (53.2% vs 57.5% p = 0.36), but pCR in Arm A was higher than Arm C (53.2% vs 31.0% p < 0.001). In non-prespecified analysis, pCR in Arm B was also higher than Arm C (57.5% vs 31.0% p < 0.001). Among pts ineligible for BCS at screening (n = 141), 62% were eligible after NAC in Arm A vs 44% each in Arms B (p = 0.13) and C (p = 0.14). Grade 3–4 AEs (Arms A/B/C, 86%/85%/45%) and serious AEs (30%/27%/14%) neutropenia, thrombocytopenia, anemia, nausea, and vomiting were increased with the addition of Cb; V did not impact toxicity. Median cycles of NAC were not reduced with V + Cb + P or Cb + P vs P. Conclusions: Addition of V to neoadjuvant Cb + P followed by AC did not increase pCR rate in breast and nodes in stage II–III TNBC, while addition of V + Cb or Cb alone to P followed by AC did. Cb (+/– V) increased toxicity but did not impact delivery of NAC. Clinical trial information: NCT02032277.
A randomized phase III trial of cisplatin and tumor volume directed irradiation followed by carboplatin and paclitaxel vs. carboplatin and paclitaxel for optimally debulked, advanced endometrial carcinoma.
Authors: Matei Daniela , Filiaci Virginia L. , Randall Marcus , Steinhoff Margaret , DiSilvestro Paul , Moxley Katherine M. , Kim Byoung , Powell Matthew A. , O'Malley David M. , Spirtos Nicola M. , Tewari Krishnansu Sujata , Richards Wm Edward , Nakayama John , Mutch David Gardner , Miller David S. 
Published: September 2018

5505 Background: Patients with stage III/IVA uterine cancer (UC) carry high risk of systemic and local recurrence. Chemotherapy was shown to reduce systemic recurrence, however the risk of local failure remains high. Methods: The primary endpoint of this open label, randomized phase III trial was to determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (C-RT, experimental arm) reduces the rate of recurrence or death (i.e., increases recurrence-free survival, RFS) when compared to carboplatin and paclitaxel for 6 cycles (CT, control arm) in patients with stages III-IVA (<2 cm residual disease) or FIGO 2009 stage I/II serous or clear cell UC and positive cytology. Secondary objectives were assessment of overall survival (OS), acute and late toxicities, and quality of life. A 28.5% reduction in the rate of recurrence or death was considered significant. Treatment randomization and analysis were stratified by gross residual tumor and age. Results: Between 6/2009 and 7/2014, 813 patients were enrolled and randomized (407 C-RT and 406-CT). Of those, 733 were eligible (344 C-RT and 360 CT), and 680 received the trial intervention (333 C-RT and 347 CT). Median follow up is 47 months. Patients characteristics were balanced between arms. There were 201 (58%) > grd 3 toxicity events in the C-RT arm and 227 (63%) in the CT arm. The most common > grd 3 events were myelosupression (40% vs. 52%), gastrointestinal (13% vs. 4%), metabolic (15% vs. 19%), neurological (7% vs. 6%), infectious (4% vs. 5%). Treatment hazard ratio for RFS was 0.9 (C-RT vs. CT; CI 0.74 to 1.10). C-RT reduced the incidence of vaginal (3% vs. 7%, HR = 0.36, CI 0.16 to 0.82), pelvic and paraaortic recurrences (10% vs. 21%, HR=0.43, CI 02.8 to 0.66) compared to CT, but distant recurrences were more common with C-RT vs. CT (28% vs. 21%, HR 1.36, CI 1 to 1.86). The analysis is premature for OS comparison. Conclusions: Although C-RT reduced the rate of local recurrence compared to CT; the combined modality regimen did not increase RFS in optimally debulked, stage III/IVA UC. Clinical trial information: NCT00942357.