Final efficacy and safety results of pemetrexed (pem) continuation maintenance (mtc) therapy in the elderly from the PARAMOUNT phase III study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8068-8068
Author(s):  
Cesare Gridelli ◽  
Michael Thomas ◽  
Kumar Prabhash ◽  
Claude El Kouri ◽  
Fiona Helen Blackhall ◽  
...  
Keyword(s):  
Safety Data ◽  
Dose Intensity ◽  
The Elderly ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Phase Iii Study ◽  
Continuation Maintenance ◽  
To Receive

8068 Background: The PARAMOUNT phase III trial showed that mtc pem after pem-cisplatin induction was well tolerated and effective for patients (pts) with advanced nonsquamous NSCLC. Here we present the final OS and safety data from this study in elderly (≥70 yrs) vs. non-elderly (<70 yrs) pts. Methods: In this double-blind study, 539 pts with a PS of 0/1 were randomized (2:1, stratified for stage, PS and induction response) to receive mtc pem (n=359, 500 mg/m2, day 1, 21 day cycle) or placebo (plc) (n=180). The study was powered for PFS (previously reported) and key secondary OS. Subgroup analyses were done for pts ≥70 yrs and <70 yrs. Results: Subgroups (≥70: n=92, 17%; <70: n=447, 83%) had similar baseline characteristics except for PS and sex (elderly, PS 0/1: 22%/77%, M/F: 66%/34%; non-elderly, PS 0/1: 34%/65%, M/F: 56%/44%). The median ages were 73 yrs (≥70) and 60 yrs (<70). The mean cycles received for pts ≥70 were 7.4 (range 1-36, dose intensity (DI) 91%) for pem and 4.5 for plc, and for pts <70 were 8.0 (range 1-44, DI 94%) for pem and 5.1 for plc. The OS HRs (pem vs. plc) were 0.89 (95% CI: 0.55-1.4) for ≥70 yrs and 0.75 (95% CI: 0.60-0.95, p=0.015) for<70 yrs. The median OS (95% CI) (≥70) was 13.7 mo (10.4-19.4) for pem and 12.1 mo (8.4-16.9) for plc; the median OS (95%CI) (<70) was 13.9 mo (12.5-16.1) for pem and 10.8 mo (9.5-12.9) for plc. The 1 and 2 yr OS rates (95% CI) for the elderly were 60% (45-71%) and 34% (21-47%) for pem vs. 52% (36-66%) and 28% (15-43%) for plc, respectively. For non-elderly pts, the 1 and 2 yr OS rates were 58% (52-63%) and 31% (26-37%) for pem vs. 43% (35-52%) and 19% (13-27%) for plc, respectively. The Table shows a subset of drug-related AEs. Conclusions: Continuation mtc pem had comparable survival and toxicity profiles in the ≥70 and <70 yrs subgroups. However, Gr 3/4 anemia and neutropenia were numerically higher for pts ≥70 yrs. Clinical trial information: NCT00789373. [Table: see text]

Phase III Trial of Bevacizumab in Combination With Gemcitabine and Erlotinib in Patients With Metastatic Pancreatic Cancer

2009 ◽  
Vol 27 (13) ◽  
pp. 2231-2237 ◽  
Author(s):  
Eric Van Cutsem ◽  
Walter L. Vervenne ◽  
Jaafar Bennouna ◽  
Yves Humblet ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Safety Data ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
To Receive

PurposeTreatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo.Patients and MethodsPatients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m2/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase III trial. Primary end point was OS; secondary end points included progression-free survival (PFS), disease control rate, and safety.ResultsA total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087); this difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved PFS (HR, 0.73; 95% CI, 0.61 to 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs.ConclusionThe primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib.

scholarly journals Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study

2017 ◽  
Vol 77 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Josef S Smolen ◽  
Jung-Yoon Choe ◽  
Nenad Prodanovic ◽  
Jaroslaw Niebrzydowski ◽  
Ivan Staykov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transition Period ◽  
Phase Iii ◽  
Double Blind ◽  
Treatment Groups ◽  
American College Of Rheumatology ◽  
Registration Number ◽  
Phase Iii Study ◽  
Transition Study ◽  
To Receive

ObjectivesEfficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2.MethodsPatients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78.ResultsEfficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%–69.4% with INF/INF and 65.6%–68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively.ConclusionsThe efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2.Trial registration numberNCT01936181; EudraCT number: 2012-005733-37.

Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10015-10015 ◽  
Author(s):  
S. George ◽  
J. Y. Blay ◽  
P. G. Casali ◽  
A. Le Cesne ◽  
J. A. Morgan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Safety Data ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Sunitinib Malate ◽  
Phase Iii Study ◽  
Multitargeted Tyrosine Kinase Inhibitor ◽  
Dosing Strategy ◽  
To Receive ◽  
Advanced Gist

10015 Background: SU, an oral multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, RET and FLT3, is approved multinationally for the treatment of imatinib (IM)-resistant or -intolerant GIST. SU 50 mg/d on a 4/2 schedule (6-wk cycles: 4 wks on treatment, 2 wks off) has demonstrated efficacy and acceptable tolerability in pts with advanced IM-resistant GIST. The current study assesses the efficacy and safety of CDD of SU in this pt population. Methods: In this multicenter phase (ph) II trial, pts with IM-resistant/intolerant GIST were randomized to receive morning or evening dosing of SU 37.5 mg daily. The primary endpoint was clinical benefit rate (CBR; percentage of pts with confirmed CR, PR or SD for =24 wks per RECIST). Investigator-assessed efficacy and safety data compiled in this ph II study and an earlier ph III study were compared informally, and the PK of SU and its metabolite were also analyzed. Results: Of 61 pts randomized, 60 received treatment with SU (30 pts/arm; ITT population). At a median duration on study of 30 wks (range: 4–52+), 33 pts remain on study and 27 have discontinued. The SU dose was reduced to 25 mg/d in 9 pts due to AEs. The most common non-hematologic AEs of any cause (primarily grade [gr] 1/2) were diarrhea (40%), asthenia (38%) and fatigue (35%). Gr 3 AEs were asthenia (13%), fatigue (7%) and diarrhea (7%); gr 4 abdominal pain was reported in 3% pts. Hematologic toxicities included gr 3 anemia (10%), neutropenia (17%, all non-febrile) and thrombocytopenia (7%) and gr 4 anemia (3%). Toxicities were similar in the morning and evening dosing groups. Preliminary PK data indicated no unexpected accumulation with CDD. To date, median PFS is 27 wks (CI: 24–41) and overall CBR is 24%, including 11% pts with PRs, which compares favorably with results obtained with the approved regimen of SU 50 mg/d on the 4/2 schedule (N=207; PR: 7%; CBR: 25%; PFS 28 wks [CI: 14–34]; phase III study). Conclusions: SU is well tolerated and clinically active when given as 37.5 mg CDD in pts with IM- resistant/-intolerant GIST. The AE profile for SU CDD appears similar to that of the 4/2 schedule. Morning and evening dosing seem to have similar tolerability. SU CDD appears to be a safe and effective alternative dosing strategy for pts with IM-resistant/intolerant GIST. No significant financial relationships to disclose.

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]

Updated safety results from EXIST-2: Everolimus therapy for angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4632-4632
Author(s):  
John Bissler ◽  
Christopher Kingswood ◽  
B. A. Zonnenberg ◽  
Michael Frost ◽  
Elena Belousova ◽  
...  
Keyword(s):  
Data Analysis ◽  
Disease Progression ◽  
Response Rate ◽  
Safety Data ◽  
Study Drug ◽  
Double Blind Study ◽  
Double Blind ◽  
Initial Analysis ◽  
Response Status ◽  
To Receive

4632 Background: EXIST-2 (NCT00790400) is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of everolimus, an oral mTOR inhibitor, for treating AML in patients with TSC or sLAM. We have previously reported that everolimus resulted in a significantly higher AML response rate vs placebo (41.8% vs 0%; 95% CI: 23.5–58.4; p<0.0001) with a consistent safety profile (Bissler et al. J Am Soc Nephrol. 22, 2011, Abstract LB-PO3159). Here we present a 90-day safety update. Methods: 118 eligible patients were randomized 2:1 to receive everolimus 10 mg daily (n=79) or placebo (n=39). The primary efficacy endpoint was AML response rate (proportion of patients with best overall AML response status of “response”). Original cut-off date for data analysis was 30 Jun 2011. An updated analysis of the safety data for the safety set (all patients receiving ≥1 dose of double-blind study drug with a valid post-baseline assessment) to 14 Oct 2011 are presented here. Results: As of 14 Oct 2011, median treatment duration was 48.1 and 45.0 weeks for everolimus and placebo arms, respectively. Discontinuations in the double-blind period were the same in the everolimus arm as the initial analysis, but had increased by 4 patients in the placebo arm since initial analysis (3 due to disease progression, 1 withdrew consent). The majority of adverse events (AEs) continued to be grade 1 or 2; the incidence of serious AEs was slightly higher than initially reported, particularly in the placebo arm (everolimus 20.3%, placebo 23.1%). AE incidence leading to discontinuation was the same as initially reported (everolimus 3.8%, placebo 10.3%). In the updated data, 3 additional everolimus patients required dose interruption or reduction due to AEs; dose reduction/interruption remained more common in the everolimus arm (51.9% vs. 20.5%). Conclusions: Overall, the 90-day updated safety data analysis from the EXIST-2 trial has not revealed any additional safety concerns. No other patients receiving everolimus withdrew for any reason, whereas 3 more patients receiving placebo withdrew due to disease progression.

A phase III, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS10084-TPS10084
Author(s):  
Danny Rischin ◽  
Matthew G. Fury ◽  
Israel Lowy ◽  
Elizabeth Stankevich ◽  
Hyunsil Han ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Recurrence ◽  
Phase Iii ◽  
Asia Pacific ◽  
Disease Stage ◽  
Double Blind Study ◽  
Extracapsular Extension ◽  
Double Blind ◽  
Post Surgery ◽  
To Receive

TPS10084 Background: CSCC is the second most common skin cancer. While the surgical cure rate for CSCC is > 95%, a proportion of pts are considered to have high risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti‒PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Methods: This randomized, placebo-controlled, double-blind, multicenter, Phase 3 study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT (NCT03969004). Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion, and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomized 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. This study is currently open for enrollment. Clinical trial information: NCT03969004.

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.

Improved survival outcomes in clinically relevant patient subgroups from COU-AA-301, a phase III study of abiraterone acetate (AA) plus prednisone (P) in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel-based chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
H. I. Scher ◽  
C. Logothetis ◽  
A. Molina ◽  
O. B. Goodman ◽  
C. N. Sternberg ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Androgen Synthesis ◽  
Phase Iii Study ◽  
Study Population ◽  
Grade 3 ◽  
Patient Subgroups

4 Background: AA is a selective androgen biosynthesis inhibitor that blocks the action of CYP17. Preclinical and early clinical studies suggest that AA potently inhibits persistent androgen synthesis from adrenal and intratumoral sources, thus suppressing an important growth stimulus for mCRPC. Methods: COU-AA-301 ( NCT00638690 ) is an international, randomized, double blind study of AA (1,000 mg + P 5 mg po BID) vs placebo + P administered to men with mCRPC progressing after docetaxel-based chemo. OS is the primary endpoint. Patients treated with previous ketoconazole or > 2 prior chemo regimens were excluded. Results: Data are drawn from a planned, stratified interim analysis, unblinded in August 2010, based on significant OS improvement in the AA + P treatment group compared to the placebo + P group [median OS 14.8 vs.10.9 months; HR = 0.646 (0.54-0.77), P < 0.0001]. A subgroup analysis for OS is presented in the table. Mineralocorticoid- related AEs were more common in the AA arm vs placebo: fluid retention 30.5% vs 22.3%, hypokalemia 17.1% vs 8.4%; but grade 3/4 hypokalemia (3.8% vs 0.8%), and grade 3/4 hypertension (1.3% vs 0.3%) were infrequent. LFT abnormalities were observed in 10.4% AA vs 8.1% placebo; and cardiac disorders were observed in 13.3% AA vs 10.4% placebo. Conclusions: AA significantly prolongs OS in patients with mCRPC who have progressed after docetaxel-based chemo. AA's favorable treatment effect on OS, observed across multiple patient subgroups (HR range 0.59 – 0.74 vs placebo + P), was consistent with the survival benefit for the overall study population. [Table: see text] [Table: see text]

Meta-analysis of anti-VEGF class adverse events from three double-blind (db), placebo (pbo)-controlled phase III trials with IV aflibercept (Afl).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
Josep Tabernero ◽  
Carmen Joseph Allegra ◽  
Philippe R Rougier ◽  
Giorgio Scagliotti ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Safety Data ◽  
Dose Intensity ◽  
Phase Iii ◽  
Double Blind ◽  
Anti Vegf ◽  
Increased Risk ◽  
Grade 3

3579 Background: Three db, pbo-controlled studies were conducted with IV Afl in metastatic cancer patients (pts) (colorectal [CRC], Afl + FOLFIRI [WCGC 2011, abstract O-0024]; lung [LC], Afl + docetaxel [WCLC 2011, abstract 511]; and pancreatic [PC], Afl + gemcitabine [WCGC 2009 abstract O-0006]). Each study used the same weekly Afl dose intensity (4 mg/kg q2w for CRC and PC; 6 mg/kg q3w for LC). A safety meta-analysis of anti-VEGF class adverse events (AEs) was performed on data from these studies. Methods: A fixed-effect logistic regression model was used, including study, treatment, and study-by-treatment interaction factors as covariates to test the consistency of treatment effect across studies for each of the considered AE. When no evidence of heterogeneity of treatment effects was found across studies, relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Summary incidences (% of pts) and RR are presented for NCI grade 3-4 events. Results: Safety data from a total of 2662 pts (Afl, 1333; pbo, 1329) were included for analysis. Among pts treated with Afl, 0.4 and 0.5% experienced grade 4 hypertension and nephrotic syndrome, respectively. Conclusions: The addition of Afl to concurrent chemotherapies did not increase the risk of VTE. The risk of grade 3-4 anti-VEGF class AEs was increased when adding Afl to concurrent chemotherapies. This increased risk was statistically significant only for hypertension, proteinuria, and hemorrhage. Further analyses, when more data are available, should improve the precision of these results. [Table: see text]

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