Efficacy and safety findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5- FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4029-4029 ◽  
Author(s):  
M. Ducreux ◽  
J. Bennouna ◽  
M. Hebbar ◽  
M. Ychou ◽  
G. Lledo ◽  
...  
Keyword(s):  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
First Line ◽  
Phase Iii Trial ◽  
Intention To Treat ◽  
First Line Therapy ◽  
Best Response ◽  
Grade 3

4029 Background: X has comparable efficacy, safety and convenience benefits over 5-FU/LV (Mayo clinic) in adjuvant colon cancer and first-line MCRC. A recent phase III trial in first line MCRC showed that XELOX is well tolerated and non inferior to FOLFOX-4 for progression-free survival (PFS) [Cassidy ESMO 2006]. Methods: We initiated a phase III trial to demonstrate non inferiority in terms of best response rates (RR, RECIST) of XELOX versus FOLFOX-6 as first-line therapy in patients (pts) with MCRC. Between 16 May 03 and 31 Aug 04, 306 patients (intention to treat), were randomized to receive either XELOX (n=156: × 1,000mg/m2 bid d1–14, O 130mg/m2 d1, q3w) or FOLFOX-6 (n=150: O 100mg/m2 d1 LV 400mg/m2 2h infusion then 5-FU 400mg/m2 i.v. bolus then 2,400–3,000mg/m2 46h infusion, q2w) for 6 months. Efficacy results are presented in the per protocol population (PP) (n=284:144 pts XELOX; 140 pts FOLFOX-6). Results: Baseline characteristics were well balanced. Pts received a median of 8 and 11 cycles of XELOX (range 0–8) and FOLFOX-6 (range 0–12), respectively. Dose intensity (median) for oxaliplatin was 99.6% and 95.4% with XELOX and FOLFOX-6, respectively. Best RR (independent review, PP) was 42% and 46% with XELOX and FOLFOX-6, respectively. Difference between groups for RR was 4.7%; upper limit of 95% unilateral CI (14.4%) was below non-inferiority margin of 15%. RR by investigators (PP) was 46% for each arm. With a median follow up of 16.5 months (range 0.4–38.3), median PFS and overall survival (PP) were 9.3/19.9 vs. 9.7/18.4 months with XELOX and FOLFOX-6, respectively. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 0%, p=0.21), thrombocytopenia (12 vs. 5% p=0.052), and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001), neuropathy (8 vs. 19% p=0.003), than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% in XELOX and FOLFOX-6 arms, respectively. Conclusions: The primary endpoint has been met: XELOX is non inferior to FOLFOX-6, with a good safety profile in first-line MCRC. No significant financial relationships to disclose.

Randomized phase III trial of capecitabine/cisplatin (XP) vs. continuous infusion of 5-FU/cisplatin (FP) as first-line therapy in patients (pts) with advanced gastric cancer (AGC): Efficacy and safety results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA4018-LBA4018 ◽  
Author(s):  
Y. Kang ◽  
W. K. Kang ◽  
D. B. Shin ◽  
J. Chen ◽  
J. Xiong ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Primary Endpoint ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

LBA4018 Background: The oral fluoropyrimidine capecitabine has proven efficacy and safety in colorectal and breast cancer. Phase II data in AGC suggested that XP would show comparable efficacy to a standard FP regimen, with potential safety and convenience advantages. This phase III study evaluated XP vs. FP in first-line AGC. Methods: Pts with previously untreated measurable AGC received either oral capecitabine (1000mg/m2 bid d1–14) + cisplatin (80mg/m2 i.v. d1) q3w (XP arm) or 5-FU (800mg/m2/d continuous infusion, d1–5) + cisplatin (80mg/m2 i.v. d1) q3w (FP arm). XP requires 1 day per 3 weeks in hospital; FP requires 5 days. Pts were treated until disease progression or unacceptable toxicity. Primary endpoint: non-inferiority (NI) in progression-free survival (PFS), defined as upper limit of 95% CI of hazard ratio (HR) <1.4 (first test) and <1.25 (second test). Results: From Apr 03 to Jan 05, 316 pts were enrolled in 46 centers/13 countries. Arms were well balanced: median age (years, range) XP (56, 26–74), FP (56, 22–73); median Karnofsky PS 80 (range 70–100) in both arms; male/female (%): XP (64/36) FP (69/31). Median no. of cycles was 5 (XP and FP). Median follow-up is 22.1 months. Primary endpoint was met: HR 0.81 (95% CI 0.63–1.04). XP was superior to FP in terms of overall response rate (ORR, RECIST). Efficacy is presented in the table. Most common treatment-related grade 3/4 adverse events (XP vs. FP) were: neutropenia (16 vs. 19%), vomiting (7 vs. 9%), stomatitis (2 vs. 7%), diarrhea (5 vs. 5%), and anemia (5 vs. 3%). Other grade 3/4 events occurred in <5% of pts. The rate of all-grade hand-foot syndrome was low (22 vs. 4%). Conclusions: XP showed highly significant non-inferiority for PFS and significant superiority for ORR vs. FP with similar safety. These findings suggest that capecitabine should become the fluoropyrimidine of choice for AGC, given the efficacy, reduced hospitalization time and simplified regimen. No significant financial relationships to disclose. [Table: see text]

A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-α2a vs placebo/interferon- α2a as first-line therapy in metastatic renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
B. Escudier ◽  
P. Koralewski ◽  
A. Pluzanska ◽  
A. Ravaud ◽  
S. Bracarda ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Interferon Α2a ◽  
Phase Iii Study ◽  
Adequate Organ Function

3 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumor angiogenesis by targeting VEGF. In relapsed RCC, BEV improved time to progression compared with placebo (2.5 vs. 4.8 months). A phase III trial was conducted to evaluate the efficacy and safety of BEV in combination with interferon (IFN)-a2a as first-line treatment in metastatic (m) RCC. The final analysis of progression-free survival (PFS) and interim analysis of overall survival (OS) are presented. Methods: Nephrectomized patients with clear cell mRCC, KPS of =70%, no CNS metastases and adequate organ function received IFN- a2a (x3/week at a recommended dose of 9 MIU for up to 1 year) plus BEV (10mg/kg q2w) or placebo until disease progression. Tumor assessments were performed every 8 weeks until week 32 and 12 weekly thereafter. Patients were stratified according to country and Motzer score. Results: Between June 2004 and October 2006, 649 patients were randomized (641 treated) at 101 centers in 18 countries. The treatment arms were well balanced for prognostic factors. At the data cutoff, 505 progression events had occurred, 111 patients remained on treatment, 287 had discontinued (discontinuations due to AEs were 12% with IFN vs. 28% with IFN-a2a/BEV), and 251 died. BEV-related side effects were generally mild and consistent with previous observations. The addition of BEV to IFN-a2a significantly increased PFS (10.2 vs. 5.4 mo) (HR=0.63; p<0.0001) and objective tumor response rate (30.6% vs. 12.4%; p<0.0001). A trend toward improved OS was observed with the addition of BEV to IFN-a2a (p=0.0670). Conclusions: BEV improves PFS when combined with IFN-a2a in mRCC. No unexpected safety events were observed. [Table: see text] [Table: see text]

Activity of fractionated radioimmunotherapy (RAIT) with 90Y clivatuzumab tetraxetan (90Y-hPAM4) plus gemcitabine (Gem) in advanced pancreatic cancer (APC): Final results from a two-part study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 227-227
Author(s):  
Allyson J. Ocean ◽  
Michael J. Guarino ◽  
Kenneth Lee Pennington ◽  
Gregory M. Springett ◽  
Seza A Gulec ◽  
...  
Keyword(s):  
Survival Data ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Comparable Efficacy ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response ◽  
Grade 3 ◽  
Higher Doses

227 Background: A Phase I/II trial was undertaken to evaluate repeated cycles of 90Y-labeled anti-mucin humanized mAb (90Y-hPAM4) plus Gem as first-line therapy in Stage 3-4 APC. Methods: Pts received Gem once-weekly x 4 with 90Y-hPAM4 on wks 2, 3 and 4, with cycles repeated until progression or unacceptable toxicity. In Part I, pts were treated in cohorts with escalating 90Y doses and Gem fixed at a low 200 mg/m2 dose for radiosensitization. In Part II, the Gem doses were increased up to standard levels, with 90Y doses fixed for first cycle, but decreased for subsequent cycles. Tumor responses were assessed by CT, FDG/PET and serum CA19-9; safety by NCI-CTCv3. Results: Of 100 untreated pts enrolled, 10 withdrew early, while 90 (73 stage IV) received 1-4 cycles. In Part I, 38 pts received 90Y-hPAM4 weekly x 3 at 90Y doses of 6.5 (N=4), 9 (N=12), 12 (N=17) or 15 (N=5) mCi/m2, with the same cycle repeated 1-3 times in 13 pts. Grade 3-4 platelets or ANC developed in 20/38 (53%) after cycle 1 (all reversible to Grade 1) and in all retreated pts (irreversible in 4/9 pts at 12 or 15 mCi/m2). There were 3 febrile neutropenias, 4 other infections treated with IV antibiotics, but no major bleeding or other AEs. By CT-RECIST criteria, 6 pts (16%) had PRs and 16 (42%) had stabilization as best response (58% disease control). After cycle 1, 52% (13/25) with PET-avid images became negative or had >25% SUV reduction, and 33% (9/27) with elevated CA19-9 levels decreased by >50%. The median overall survival was 7.7 mo., but 11.8 mo. for retreated pts [46% (6/13) survived ≥1 yr.], with improved efficacy at higher 90Y doses. In Part II, 52 pts received 12 mCi/m2 90Y-hPAM4 x 3 with Gem doses of 200 (N=17), 600 (N=8) or 1000 mg/m2 (N=27), with 13 pts now retreated at 90Y doses of 6.5 or 9 mCi/m2. Results so far indicate no advantage to giving higher doses of Gem with RAIT. Toxicity, response and survival data for this group will be presented at the conference. Conclusions: Fractionated RAIT with 90Y-hPAM4 combined with low-dose gemcitabine appears to be a manageable and active first-line therapy for APC. It may provide comparable efficacy yet less toxicity compared to other regimens.

Phase III study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with metastatic pancreatic adenocarcinoma (mPC): Subgroup analysis of Canadian pts from the MPACT trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 439-439
Author(s):  
Mustapha Ali Tehfe ◽  
Scot D. Dowden ◽  
Hagen F. Kennecke ◽  
Robert Hassan El-Maraghi ◽  
Bernard Lesperance ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Pancreatic Head ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Common Grade ◽  
Grade 3 ◽  
Intent To Treat

439 Background: Weekly nab-P + Gem is a new option for first-line treatment (Tx) of mPC. In the MPACT trial, nab-P/Gem demonstrated superior overall survival (OS; primary endpoint) vs Gem alone as first-line Tx of mPC (Table). Here we report a subgroup analyses evaluating the efficacy and safety outcomes with nab-P + Gem vs Gem alone from the Canadian cohort of the MPACT trial. Methods: Previously untreated pts (N = 861) with mPC were randomized 1:1 (stratified by Karnofsky Performance Status [KPS], region, and the presence of liver metastases) to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle or Gem 1000 mg/m2 weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of each 28-day cycle (cycle ≥ 2). Results: 63 pts from Canada enrolled in the MPACT trial. Baseline pt characteristics were well balanced. Median age was 61 years and KPS was similar for both groups and comparable to the intent-to-treat (ITT) populations. Primary lesion in the pancreatic head was more common among pts in the nab-P + Gem vs Gem arm (55% vs 30%); use of biliary stent was similar (33% nab-P + Gem; 27% Gem). Median OS and progression-free survival (PFS) were longer with nab-P + Gem vs Gem (Table). Median Tx duration was 4.2 mo with nab-P + Gem vs 3.2 mo with Gem. Use of subsequent therapy was 30% in the nab-P + Gem arm vs 43% in the Gem arm. The median relative dose intensity for Gem was similar in each arm (81% nab-P + Gem vs 85% Gem). The most common grade ≥ 3 AEs for nab-P + Gem vs Gem were neutropenia (22% vs 10%), fatigue (34% vs 33%), and neuropathy (25% vs 0%). Conclusions: Canadian pts participating in MPACT were similar to the ITT population and nab-P + Gem was well tolerated and showed improved median OS, PFS, and ORR vs Gem alone, although not statistically significant (likely due to the small number of pts). Clinical trial information: NCT00844649. [Table: see text]

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 2006-2012 ◽  
Author(s):  
Jim Cassidy ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Phase II study of gemcitabine (Gem) + docetaxel (D) in combination with trastuzumab (T) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10730-10730
Author(s):  
D. R. Fescina ◽  
W. Gradishar ◽  
M. Orlando ◽  
J. Rubinsak ◽  
L. Haney ◽  
...  
Keyword(s):  
Single Agent ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line Therapy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

10730 Background: Addition of T to chemotherapy (chemo) is assoc. with improved overall survival (OS) in pts with HER2+ tumors. Combination chemo has shown improvements in PFS and OS over single agent in recent phase III studies. Pre-clinical models suggest that the combination of G and D appears to be synergistic and that either agent is also synergistic with T. Objectives: This multi-institutional study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of G + D + T as first-line therapy for MBC pts. Design: Pts with measurable HER2-overexpressing (FISH+) MBC, no prior chemo in the metastatic setting, adequate end-organ function and PS 0–2, received Gem 1,000 mg/m2 over 30 min on days 1 and 8 + D 75 mg/m2 day 1 and T on day 1 (8 mg/kg over 90 min on cycle 1, then 6 mg/kg over 30 min on subsequent cycles) of a 21-day cycle, until progressive disease or undue toxicity. Results: 8 pts have been enrolled over a period of 16 months. Median age: 53 years (range 40–74); ER status ±: 5/3 pts; ECOG PS 0 = 3 pts, 1 = 4 pts, 2 = 1 pt; Prior adjuvant therapy: Chemo ± Hormonal 3, Hormonal only 3, T 1. Sites of Disease: All pts had visceral involvement (Lung 4, Liver 5) and 5 pts ≥ 2 sites of metastatic disease. Total number of cycles administered was 52; median per pt. 7 (range 4–10). Median delivered dose intensity for G, D and T was 91%, 92% and 100% respectively. Toxicity was generally manageable. One pt discontinued therapy due to adverse events (grade 3 pneumonitis). Grade 3/4 neutropenia occurred in 27% and 10% of cycles; no grade 3/4 anemia or thrombocytopenia were recorded; Non-Heme toxicities of grade 2/3, included with dyspnea (0/2 pts), emesis (2/1), fatigue (4/1), diarrhea (1/1), dehydration (0/1), constipation (1/0). Complete alopecia was observed in 2 pts. No symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 8): CR 3, PR 4, SD 1, PD 0, for an ORR of 7 out of 8 pts or 88% (95% CI: 47%–100%). Only 3 pts have progressed, and no pt has died. Progression-free survival at 1 year is 58%. Conclusion: According to this limited experience, the combination of G + D + T in front-line MBC is well tolerated and active. Study was discontinued due to slow accrual as of Feb 2004. Supported by Eli Lilly & Company. [Table: see text]

PALETTE: A randomized, double-blind, phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy—An EORTC STBSG Global Network Study (EORTC 62072).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA10002-LBA10002 ◽  
Author(s):  
W. T. Van Der Graaf ◽  
J. Blay ◽  
S. P. Chawla ◽  
D. Kim ◽  
B. Bui Nguyen ◽  
...  
Keyword(s):  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Global Network ◽  
Phase Iii ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Independent Review ◽  
Grade 3

LBA10002 Background: Pazopanib, a multi targeted angiogenesis inhibitor, has demonstrated single-agent activity in pts with advanced STS. The efficacy and safety of pazopanib versus placebo as second or later line treatment were evaluated in pts with metastatic STS in a multi-center, international, double-blind, placebo-controlled phase III trial. Methods: Pts ≥18 years of age with angiogenesis inhibitor-naïve, histologically proven, metastatic STS, who failed at least one anthracycline containing regimen, could enter the study. They should have ≥1 measurable baseline lesion (per RECIST v1.0), WHO PS 0-1, adequate bone marrow, coagulation, hepatic and renal function, no poorly controlled hypertension, no bleeding diathesis, and no CNS involvement. The study has been conducted by EORTC and GSK in collaboration with 72 sarcoma centers worldwide. Pts were randomized 2:1 to receive either pazopanib 800 mg once daily or placebo until tumor progression, unacceptable toxicity, death, or pt’s request. Results: A total of 369 randomized pts (246 pazopanib, 123 placebo), median age of 56 years, participated in the study (EORTC 45 %, other 55%). Median duration of follow-up at clinical cut-off date is 15 months. The primary endpoint of progression-free survival (PFS) per independent review is significantly prolonged with pazopanib (median: 20 vs 7 weeks; HR=0.31, 95% CI 0.24-0.40 ; P<0.0001). The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo (median: 11.9 vs 10.4 months, HR=0.83, 95% CI 0.62-1.09). Main on-therapy grade 3-4 toxicities in the pazopanib vs placebo arm respectively: fatigue (13%, 6%), hypertension (7%, nil), anorexia (6%, nil), and diarrhea (5%, 1%). Similarly, thromboembolic events (grade 3-5 ) (3%, 2%), LVEF drop of >15% (8%, 3%). Median relative dose intensity of pazopanib was 768 mg daily. Conclusions: Pazopanib is an active drug in anthracycline pretreated metastatic STS pts with an increase in median PFS of 13 weeks.

scholarly journals Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance)

2015 ◽  
Vol 33 (21) ◽  
pp. 2361-2369 ◽  
Author(s):  
Hope S. Rugo ◽  
William T. Barry ◽  
Alvaro Moreno-Aspitia ◽  
Alan P. Lyss ◽  
Constance Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Nonhematologic Toxicity

Purpose We compared nab-paclitaxel or ixabepilone once per week to paclitaxel with bevacizumab as first-line therapy for patients with advanced breast cancer (BC) to evaluate progression-free survival (PFS) for nab-paclitaxel or ixabepilone versus paclitaxel. Patients and Methods Eligible patients were age ≥ 18 years with chemotherapy-naive advanced BC. Patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m2 (arm A), nab-paclitaxel 150 mg/m2 (arm B), or ixabepilone 16 mg/m2 (arm C), once per week for 3 of 4 weeks. Planned enrollment was 900 patients, which would give 88% power to detect a hazard ratio of 0.73. Results In all, 799 patients were enrolled, and 783 received treatment (97% received bevacizumab). Arm C was closed for futility at the first interim analysis (n = 241), and arm A (n = 267) and arm B (n = 275) were closed for futility at the second interim analysis. Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P < .001), and nab-paclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45; P = .054). Results were concordant with overall survival; time to treatment failure was significantly shorter in both experimental arms v paclitaxel. Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nab-paclitaxel, with more frequent and earlier dose reductions. Conclusion In patients with chemotherapy-naive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting.

Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7592-7592 ◽  
Author(s):  
Markus Frederic Renschler ◽  
Isamu Okamoto ◽  
Jeremy K. Hon ◽  
Vera Hirsh ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Iii ◽  
Positive Trend ◽  
First Line ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
And Gender

7592 Background: Treatment of advanced NSCLC differs by histology, with fewer options and poorer outcomes in pts with squamous histology. In a phase III trial of nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, the primary endpoint of ORR was significantly improved from 25% to 33%, p = 0.005, with a 1-month improvement in OS (p = NS) and improved safety. This analysis evaluated efficacy and safety by histology. Methods: Pts with untreated stage IIIB/IV NSCLC were randomized 1:1 (stratified by age, histology, region, stage, and gender) to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day 1 q 21 days. ORR and PFS were determined by blinded centralized review. Results: In squamous pts, nab-P/C produced a significantly higher ORR (41% vs 24%, p < 0.001), similar PFS (5.6 vs 5.7 mo, HR: 0.865) and >1-month improvement in OS (10.7 vs 9.5 mo, HR: 0.890) vs sb-P/C (Table). nab-P/C was as effective as sb-P/C in nonsquamous pts for ORR (26% vs 25%, p = 0.808), PFS (6.9 vs 6.5 mo, HR: 0.933), and OS (13.1 vs 13.0 mo, HR: 0.950). In both squamous and nonsquamous pts, nab-P/C vs sb-P/C produced lower rates of grade 3/4 neuropathy (3% vs 11% and 3% vs 12%, respectively, p < 0.001 both), neutropenia (43% vs 51%, p = NS, and 50% vs 63%, p = 0.008), and higher but manageable rates of anemia (27% vs 4% and 28% vs 9%, p < 0.001 both) and thrombocytopenia (21% vs 7% and 16% vs 11%, p < 0.001 both). Conclusions: In pts with advanced NSCLC, nab-P/C demonstrated a favorable risk-benefit profile as a first-line therapy regardless of histology. Significantly improved ORR and a positive trend in OS were observed in pts with squamous histology. [Table: see text]

Safety and quality of life (QoL) findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5-FU/LV + O (FOLFOX-6) in metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4099-4099 ◽  
Author(s):  
M. Hebbar ◽  
J. Bennouna ◽  
V. Boige ◽  
M. Ychou ◽  
G. Lledo ◽  
...  
Keyword(s):  
Safety Profile ◽  
Compliance Rate ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Final Visit ◽  
First Line ◽  
Best Response ◽  
Grade 3 ◽  
Eortc Qlq

4099 Background: A recent phase III trial in first-line MCRC showed that XELOX is non-inferior to infusional 5-FU + oxaliplatin (FOLFOX-4) for progression-free survival (PFS) [Cassidy ESMO 2006]. Here we present safety and QoL findings from a study of XELOX vs. FOLFOX-6 in first-line MCRC. Methods: Between 16 May 03 and 31 Aug 04, 306 patients (pts) were randomized to receive either XELOX (156 pts: × 1,000mg/m2 bid d1–14, O 130mg/m2 d1, q3w) or FOLFOX-6 (150 pts: O 100mg/m2 d1 LV 400mg/m2 2h infusion then 5-FU 400mg/m2 i.v. bolus then 2,400–3,000mg/m2 46h infusion, q2w) for 6 months. Primary objective: demonstrate non inferiority of XELOX in terms of best response rate (RECIST). Secondary objectives: evaluate QoL and pt satisfaction with care by EORTC QLQ-C30 and FACIT (chemotherapy convenience and satisfaction) questionnaires. Pts completed questionnaires at baseline, before cycles 3/4, 6/8 and at final visit in XELOX/FOLFOX-6 arms, respectively. Results: 245 pts (QLQ-C30) and 225 pts (satisfaction) were evaluable for QoL. The compliance rate was >70%. At baseline, QoL scores were not significantly different. QLQ-C30 functional and symptomatic scores were stable in both arms. According to FACIT, there was no difference between arms, although XELOX-treated pts wasted less hours of their free time than those on FOLFOX-6: 10±23 vs. 37±68 hours, respectively (p=0.007). XELOX was a more ‘comfortable’ treatment (p<0.001 vs. FOLFOX-6 at 2nd evaluation and p=0.009 at 3rd evaluation). Safety profile was acceptable in both arms. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 1% p=0.215), thrombocytopenia (12 vs. 5% p=0.052) and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001) and neuropathy (8 vs. 19% p=0.003) than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% for XELOX and FOLFOX-6 arms, respectively. Conclusions: XELOX is comparable to FOLFOX-6 in terms of QoL with less time wasted receiving XELOX. XELOX is also non-inferior to FOLFOX-6 (primary endpoint met/presented at same meeting) with a similar safety profile in first-line MCRC. No significant financial relationships to disclose.

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