Primary results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Masanori Terashima ◽  
Yuichiro Doki ◽  
Yukinori Kurokawa ◽  
Junki Mizusawa ◽  
Hitoshi Katai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Operation Time ◽  
Final Analysis ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Hospital Death ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Grade 3

5 Background: The role of bursectomy dissecting the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon for preventing peritoneal metastasis had long been controversial. We conducted a phase III trial evaluating the role of bursectomy in patients with subserosal (SS) / serosal (SE) gastric cancer. Patient accrual had been completed on Mar. 2015. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival. A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: Between Jun 2010 and Mar 2015, 1,204 patients were accrued from 57 institutions (non-bursectomy 602, bursectomy 602). Patients’ background and operative procedures were well balanced between the arms. After completion of patient enrollment, the second interim analysis was performed on Sep 2016, with 54% (196/363) of the expected events observed. The 3y-survival were 86.0% (95%CI, 82.7 to 88.7) in non-bursectomy arm and 83.3% (95%CI, 79.6 to 86.3) in bursectomy arm. Hazard ratio for bursectomy was 1.075 (98.5%CI: 0.760 to 1.520) with predictive probability in favor of bursectomy at the final analysis of 12.7%. These results led to early study termination based on the recommendation of the Data and Safety Monitoring Committee. Operation time was longer (median 222 min vs 254 min) and blood loss was larger (230 ml vs 330 ml) in bursectomy arm; however, the incidence of patients received blood transfusion was not different between the arms (4.8% vs 4.5%). Although the incidence of pancreatic fistula was a bit higher in bursectomy arm (2.5% vs 4.8%), the incidence of Grade 3 or higher complications was not different between the arms (11.6% vs 13.3%). Five patients in non-bursectomy arm and one patient in bursectomy showed in-hospital death. Conclusions: Although bursectomy can be safely performed without increasing morbidity and mortality, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.

Randomized phase III trial of standard D2 versus D2 + para-aortic lymph node (PAN) dissection (D) for clinically M0 advanced gastric cancer: JCOG9501

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA4015-LBA4015 ◽  
Author(s):  
M. Sasako ◽  
T. Sano ◽  
S. Yamamoto ◽  
A. Nashimoto ◽  
A. Kurita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Disease Free Survival ◽  
Operation Time ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Rank Test ◽  
R0 Resection ◽  
Eligibility Criteria ◽  
Curative Intent

LBA4015 Background: The INT-0116 study proved the efficacy of radiochemotherapy after R0 resection for gastric cancer and thus the importance of the local control and the insufficiency of D0/1 surgery. Recently D2 surgery was for the first time proven to improve the survival compared with D1 in a Taiwanese RCT (Lancet Oncol 2006). In our study, D2+PAND was compared with D2 in a RCT. Low operative mortality has been reported (Sano et al. J Clin Oncol 2004) and we now present the survival results. Methods: Eligibility criteria included; histologically proven adenocarcinoma, cT2b-T4, cM0, no macroscopic metastasis to the PAN, negative lavage cytology, adequate organ function, and age <76. Linitis plastica was excluded. Eligible pts were randomly assigned to D2 with or without PAND during surgery. All patients were followed without adjuvant therapy until recurrence. The primary endpoint was overall survival (OS) to be compared by stratified log-rank test. Assuming 256 eligible pts in each arm, the study had 75% power to detect 0.73 hazard ratio for D2+PAND to D2 in OS at 0.05 one-sided alpha. Results: Between 07/1995 and 04/2001, 523 pts were randomized (263 to D2 and 260 to D2+PAND). Baseline characteristics were well balanced between the arms. At the time of the final analysis on 23/03/06, 191 (96 and 95, in D2 and D2+PAND, respectively) had died. The 3- and 5-year OS were 76% and 69% in D2 and 76% and 70% in D2+PAND, respectively (p = 0.57, Hazard ratio was 1.03 (95% CI: 0.77–1.37)). Disease free survival did not show any difference between the groups as well. Median operation time was 63 minutes longer and median blood loss was 230 ml larger in D2+PAND than in D2. There was no difference in the incidence of major surgical complications and hospital mortality (0.8% in both arms). Conclusions: D2 or D2+PAND could be carried out safely and showed excellent survival for advanced gastric cancer treated with curative intent. PAND could not improve the survival achieved by D2. General use of PAND should be avoided. No significant financial relationships to disclose.

Final results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 206-206
Author(s):  
Hitoshi Katai ◽  
Yuichiro Doki ◽  
Yukinori Kurokawa ◽  
Junki Mizusawa ◽  
Takaki Yoshikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Interim Analysis ◽  
Multivariable Analysis ◽  
Final Analysis ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Japanese Classification ◽  
Frequent Site ◽  
Type 3

206 Background: We previously reported that the superiority of bursectomy was not demonstrated for subserosal(SS)/serosal(SE) gastric cancer by the second interim analysis performed with 54% of the expected events observed. We report the final 5-year follow-up data. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach, cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival (OS), and secondary endpoint was relapse-free survival (RFS). A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: A total of 1204 eligible patients with cT3 / cT4a gastric cancer were randomized (602 in non-bursectomy arm, 602 in bursectomy arm, respectively). Patients’ background and operative procedures were well balanced between the arms. The 5y-OS were 76.5% (95% CI, 72.8 to 79.7) in non-bursectomy arm and 74.9% (71.2 to 78.2) in bursectomy arm. Hazard ratio (HR) for bursectomy was 1.03 (0.83-1.27, one-sided p = 0.598). The 5y-RFS were 70.7% (66.9 to 74.2) in non-bursectomy arm and 66.8% (62.9 to 70.5) in bursectomy arm [HR: 1.131 (0.93-1.38)]. HR for death was almost similar in all sub-categories (0.73-1.29) except cN2 (13th edition of Japanese Classification of Gastric Carcinoma); HR classified by cN was 1.06 (95% CI: 0.75-1.49) for cN0 (n = 521), 1.25 (0.92-1.71) for cN1 (n = 525), and 0.59 (0.32-1.06) for cN2 (n = 158) (p = 0.048 for interaction). The most frequent site of recurrence was the peritoneum [74 (12.3%) in non-bursectomy arm, 73 (12.1%) in bursectomy arm], and bursectomy arm showed a trend of increasing liver metastasis (n = 45, 7.5%) as compared with non-bursectomy arm (n = 33, 5.5%). Six independent poor prognostic factors were identified by multivariable analysis for OS: age ≥ 66 (vs. ≤ 65) (HR, 1.30; 95% CI, 1.04-1.62), macroscopic type 3/5 (vs. type 0/1/2) (1.43; 1.15-1.79), total gastrectomy (vs. distal gastrectomy) (1.44; 1.03-2.02), pT3 (vs. pT1-2) (1.77; 1.17-2.676), pT4 (vs. pT1-2) (3.00; 1.99-4.53), pN1 (vs. pN0) (2.34; 1.52-3.59), pN2-3b (vs. pN0)(4.02; 2.82-5.74) and adjuvant chemotherapy (vs. without chemotherapy) (0.53; 0.42-0.67), but bursectomy was not significant (1.10 0.89-1.36). Conclusions: In the final analysis as well as in the interim analysis, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.

Phase III trial of adjuvant capecitabine/cisplatin (XP) versus capecitabine/cisplatin/RT (XPRT) in resected gastric cancer with D2 nodal dissection (ARTIST trial): Safety analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4537-4537 ◽  
Author(s):  
J. Lee ◽  
W. Kang ◽  
D. Lim ◽  
J. Park ◽  
Y. Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Chemoradiation Therapy ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Resected Gastric Cancer ◽  
Disease Free

4537 Background: Although the adjuvant chemoradiation therapy has gained popularity and has become the standard of care in patients with resected gastric cancer in U.S., the role of chemoradiation therapy after extended D2 dissection has been questioned. We conducted a phase III trial to compare capecitabine/cisplatin (XP) vs XP + radiotherapy (RT) in curatively D2 resected gastric cancer patients in terms of disease free survival and overall survival. Methods: Eligibility criteria were as follows: stage Ib (T1N1, T2bN0) - IV (M1 excluded), curatively ≥ D2 resected gastric adenocarcinoma. XP only: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 repeated every 3 weeks, 6 cycles; XP + RT: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles ⋄ RT 45 Gy (25 fractions) + X 1,650 mg/m2/d during RT ⋄ X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles. The primary endpoint is 3-year disease-free survival. Results: From October 2004 to April 2008, 458 patients (XP arm: 228 patients; XP/RT arm: 230 patients) were enrolled. In XP arm, 172 (75%) of 228 enrolled patients completed 6 cycles of chemotherapy. In XP + RT arm, 188 (82%) of 230 patients completed the full course of XP 2 cycles - X + RT - XP 2 cycles. Conclusions: Safety and feasibility analysis of the two arms will be reported at the meeting. No significant financial relationships to disclose.

Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 119-119 ◽  
Author(s):  
Jin Matsuyama ◽  
Yukinori Kurokawa ◽  
Kazuhiro Nishikawa ◽  
Yutaka Kimura ◽  
Atsushi Takeno ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Oral Intake ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Phase Iii Study

119 Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.

scholarly journals Randomized controlled Phase III trial to evaluate omentum preserving gastrectomy for patients with advanced gastric cancer (JCOG1711, ROAD-GC)

2020 ◽  
Vol 50 (11) ◽  
pp. 1321-1324
Author(s):  
Yuya Sato ◽  
Takanobu Yamada ◽  
Takaki Yoshikawa ◽  
Ryunosuke Machida ◽  
Junki Mizusawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Standard Procedure ◽  
Locally Advanced ◽  
Operation Time ◽  
Phase Iii ◽  
Current Standard ◽  
Phase Iii Trial ◽  
D2 Lymph Node Dissection ◽  
Randomized Controlled

Abstract Gastrectomy with omentectomy and D2 lymph node dissection is the current standard procedure for locally advanced gastric cancer. However, some retrospective studies have reported that omentectomy increased post-operative abdominal complications but provided no survival advantage over omentum preservation. Therefore, we plan a randomized controlled phase III trial to confirm the non-inferiority of omentum preservation compared with omentectomy in patients with cT3 (SS) or cT4a (SE) gastric cancer. A total of 1050 patients will be enrolled from 62 institutions over a period of 6.5 years. The primary end point is relapse-free survival, and the secondary end points are overall survival, blood loss, operation time and adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000036253.

Chemotherapy with FOLFOX IV in advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14112-14112
Author(s):  
M. A. Garrido. ◽  
G. Melgoza ◽  
H. Galindo ◽  
J. Madrid ◽  
C. Sanchez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Median Overall Survival ◽  
Lung Metastases ◽  
Stage Iv ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Trial ◽  
Low Toxicity ◽  
Grade 3

14112 Background: Gastric cancer is the first cause of mortality for cancer in Chile. 65% is observed in advanced form and the median survival without surgery is 5,4 months. We hypothesised that chemotherapy and specially FOLFOX IV is an active regimen and has low toxicity in patient with advanced gastric cancer. The main evaluated objectives were: response, toxicity and survival of patient with advanced gastric cancer. Methods: Patients with gastric adenocarcinoma, stage IV that accepted chemotherapy with FOLFOX IV in any time of evolution were included. The evaluation of response was obtained with CT scan every two month. The characteristics of patients, chemotherapy responses, toxicity and global survival were analysed. Results: Between November 2003 and October 2005, 20 patients were included, the median age was 51,5 years (range 28–67), 80% male. Hepatic, peritoneal and lung metastases were the principal places of dissemination. The response rate in first line was: PR 66%, SD 17%, with overall response of 83% (12 patients). In second line the response was: PR 37%, SD 63% (8 patients). The average of treatment was 5,5 months. The median of response was 5 months (2–12). The median overall survival was 12 months. 50% of patients showed toxicity; digestive grade 2 in 2 patients, neurological grade 2 in 4 patients and only 1 patient showed grade 3 toxicity. Conclusions: FOLFOX IV is an active chemotherapy regiment with low toxicity profile in advanced gastric cancer. With these results we propose a Phase III trial would be feasible to perform. No significant financial relationships to disclose.

Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA4513-LBA4513 ◽  
Author(s):  
N. Boku ◽  
S. Yamamoto ◽  
K. Shirao ◽  
T. Doi ◽  
A. Sawaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Final Analysis ◽  
Phase Iii ◽  
Survival Times ◽  
Time To Treatment Failure ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Significant Superiority

LBA4513 Backgrounds: We conducted a 3-arm phase III study to investigate superiority of CP and non-inferiority of S-1 to 5-FU for advanced gastric cancer in the primary endpoint of overall survival (OS) and secondary endpoints of response rate (RR), time to treatment failure (TTF), non-hospitalized survival (NHS) and toxicities. Methods: Treatments with 5-FU (800mg/m2/d, ci, d1–5, q4w), CP (irinotecan, 70mg/m2, div, d1&15 and cisplatin, 80mg/m2, div, d1, q4w) and S-1 (40mg/m2, b.i.d., d1- 28, q6w) were continued until disease progression or unacceptable toxicities. Tumors were evaluated every two months. With 230 patients (pts) per arm, this study had 80% power to demonstrate 10% superiority of CP and non-inferiority with 5% margin (hazard ratio, HR=1.16) of S-1 and 0.05 study-wise 1-sided alpha. Results: 704 pts having unresectable or recurrent gastric adenocarcinoma with/without target lesions (TL) were randomized between Nov 2000 and Jan 2006. Final analysis was performed in Feb 2007 when 601 pts (85%) were dead. The results of OS are shown in Table . Median TTF/NHS were 2.3M/7.2M for 5-FU, 3.7M/9.5M for CP, and 4.0M/9.2M for S-1. Incidences (%) of grade 4 neutropenia, grade ≥3 febrile neutropenia, infection with neutropenia, anorexia, diarrhea within 6M, and treatment related death (5- FU/CP/S-1) were 0/37/0, 0/9/0, 0/8/0, 13/33/12, 0/9/8, and 0/1.3/0.4. In the subset having TL, RRs of 5-FU/CP/S-1 (n=175/181/175) were 9%/38%/28%, and their median survival times (MST) were 9.0M/12.1M/10.5M and HRs to 5-FU were 0.78 (95%CI, 0.63–0.98) for CP and 0.85 (0.68–1.06) for S-1. In the subset not having TL, the MSTs of 5-FU/CP/S-1 (n=59/55/59) were 13.5M/14.4M/18.1M and HRs were 1.02 (0.68–1.55) for CP and 0.82 (0.55–1.24) for S-1. Conclusions: S-1 showed a significant non-inferiority to 5-FU. Although CP did not show statistically significant superiority to 5-FU in all pts, it may have a benefit for some subgroups such as pts with measurable metastatic diseases. [Table: see text] [Table: see text]

Randomized phase III trial of intravenous (IV) versus hepatic intra-arterial (HIA) fotemustine in patients with liver metastases from uveal melanoma: Final results of the EORTC 18021 study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8532-8532 ◽  
Author(s):  
Serge Leyvraz ◽  
Stefan Suciu ◽  
Sophie Piperno-Neumann ◽  
Jean-Francois Baurain ◽  
Marcin Zdzienicki ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Uveal Melanoma ◽  
Final Analysis ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Treatment Comparison ◽  
Phase Ii Studies ◽  
Catheter Complications ◽  
Grade 3 ◽  
Induction Cycle

8532 Background: HIA fotemustine has shown promising results in Phase II studies that led to the EORTC randomized phase III trial (18021) in unpretreated patients (pts) with liver metastases from uveal melanoma. Methods: The treatment consisted in an induction cycle of either HIA (fotemustine 100 mg/m² over 4 hours, day 1, 8, 15, 22) vs IV control arm (fotemustine 100 mg/m² over 1 hour, day 1, 8, 15). After a 5-week break, maintenance cycles were given every 3 weeks. Randomization was stratified by PS (0 vs 1), LDH (normal vs abnormal) and center. Main endpoint was overall survival (OS). Required accrual per protocol was set to 262 pts, with final analysis planned after 220 deaths (hazard ratio (HR) =0.67, power=85%, 1-sided α=2.5%). Due to poor accrual an interim analysis was done after 134 deaths, in order to test futility (power=79%). Results: Between Feb-2005- Feb-2011, 171 pts were randomized (HIA: 86, IV: 85). Characteristics: PS 1: 20%, abnormal LDH: 42%, male: 50%, median age: 59 y.; balanced between arms. In the HIA arm 20 (23%) pts never started treatment mainly due to catheter problems and 2 pts in the IV arm. In those who started the treatment, leucopenia grade 3-4 was 18% and thrombopenia grade 3-4: 21% in the HIA arm compared to 32% and 42% in the IV arm. Non-hematological grade 3-4 toxicities were minimal (GI toxicity, catheter complications). In May 2011, as the OS HR=1.097 was > critical value 0.87, the IDMC recommended stopping accrual for futility. The final results from Jan-2012 are presented in the table below. Treatment comparison adjusted by PS and LDH provided similar results. Conclusions: Even if HIA fotemustine administration could not start in 23% of pts, it led to a higher ORR and longer PFS compared to IV administration. HIA did not translate into an improvement in OS. [Table: see text]

Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA1011-LBA1011 ◽  
Author(s):  
J. Crown ◽  
V. Dieras ◽  
E. Staroslawska ◽  
D. A. Yardley ◽  
N. Davidson ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Single Agent ◽  
Final Analysis ◽  
Phase Iii ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Metastatic Setting ◽  
Hand Foot Syndrome ◽  
Ecog Ps

LBA1011 Background: Recent trials support combining an antiangiogenic agent with chemotherapy (CT) in pretreated patients (pts) with metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor demonstrated single-agent activity (11% ORR) in heavily pretreated pts with MBC. Antitumor activity with SU+C was reported in pts with advanced solid tumors. This multicenter, randomized, phase III trial (SUN 1099) compared the efficacy and safety of SU + C vs. C in pts with ABC. Methods: Eligibility criteria were: age ≥18 yrs, ECOG PS ≤1, measurable HER2-positive (FISH+, CISH+ or IHC3+) or -negative ABC, no brain metastases, prior treatment (tx) with an anthracycline and taxane in the (neo)adjuvant or metastatic setting, and ≤2 prior CT regimens for advanced disease. Prior C tx was not permitted. Pts were randomized (1:1) to combination tx with C 2,000 mg/m2/d po days 1–14 every q3w + SU 37.5 mg/d po daily, or to C 2,500 mg/m2/d days 1–14 q3w. Pts with progressive disease per RECIST on the C arm were offered single-agent SU (37.5 mg/d). Endpoints included PFS (primary), ORR, OS, QoL, and safety. Stratified and unstratified log-rank tests compared PFS between arms. Results: At the data cutoff (December 15, 2009), the ITT population comprised 442 pts: 221 in each arm with baseline characteristics well balanced between arms. The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment nor secondary endpoint of longer OS (final analysis March 10, 2010). Median PFS was 5.5 mos (95% CI 4.5–6.0) in the SU+C arm vs. 5.9 mos (95% CI 5.4–7.6) in the C arm (HR 1.224). Median OS was 16.4 mos (95% CI 13.6–18.4) for the SU+C arm and 16.5 mos (95% CI 14.2–18.6) for the C arm (HR 0.995). ORR was 18.6% for the SU+C arm and 16.3% for the C arm. The most common all causality grade 3/4 AEs (≥10%) were neutropenia (32%), hand–foot syndrome (HFS; 16%), thrombocytopenia (17%), asthenia (12%), fatigue (10%) in the SU+C arm and HFS (24%) and diarrhea (10%) in the C arm. Intended drug delivery for each arm was >80%. Discontinuations due to an AE were more frequent in the SU+C arm vs. the C arm. Discontinuations by drug in the SU+C arm: SU 39%, C 42%, SU and C 33%; in the C arm: 18%. Conclusions: Data from this randomized phase III trial do not support use of SU+C for therapy of patients with ABC. [Table: see text]

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