Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-3).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 158-158 ◽  
Author(s):  
M. H. Shah ◽  
T. Ito ◽  
C. Lombard-Bohas ◽  
E. M. Wolin ◽  
E. Van Cutsem ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Phase Ii Studies ◽  
The Impact ◽  
Patient Subgroups

158 Background: There is an unmet medical need for effective treatments for patients with advanced pNET. Systemic therapies for advanced pNET are limited both by toxicity and efficacy. Everolimus, an oral mTOR inhibitor, has shown promising antitumor activity in 2 phase II studies, leading to further investigation in the largest phase III randomized controlled trial completed in pNET patients. Methods: Patients with advanced low- or intermediate-grade pNET were randomly assigned to everolimus 10 mg/d orally + best supportive care (BSC; n = 207) or placebo + BSC (n = 203). Long-acting somatostatin analogs (SSAs) were permitted as BSC during the study. The primary endpoint was progression free survival (PFS). At progression (RECIST), patients could be unblinded and those randomly assigned to placebo were offered open-label everolimus. Results: Compared with placebo, everolimus reduced the risk of progression by 65% and increased median PFS by more than 6 months, from 4.6 to 11.0 months (HR = 0.35; 95% CI: 0.27-0.45; p < 0.0001), by investigator review (primary endpoint). Median PFS by central review was consistent (HR = 0.34; 95% CI: 0.26 to 0.44; p < 0.001] in favor of everolimus. Eighteen-month PFS estimates were 34% for everolimus (95% CI: 26-43) vs 9% (95% CI: 4-16) for placebo. Everolimus demonstrated a significant PFS benefit across all patient subgroups according to baseline characteristics and prior SSA use. Prior SSA use was 49% in the everolimus arm and 50% in the placebo arm. Updated analyses of the impact of concomitant SSA will be reported. The most common drug-related adverse events were stomatitis, rash, diarrhea, fatigue, and infections (primarily upper respiratory); most were grade 1 or 2. Stomatitis (6.9% vs 0%), anemia (6% vs 0%), and hyperglycemia (5% vs 2%) were the most common grade 3-4 events. Conclusions: Everolimus significantly prolonged PFS compared with placebo in patients with advanced pNET in this large phase III clinical trial. This benefit was seen across all patient subgroups. Treatment resulted in a significant 6.4-month prolongation in median PFS. Everolimus had an acceptable and predictable safety profile. [Table: see text]

Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA10008-LBA10008 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

Randomized phase III trial of imatinib (IM) rechallenge versus placebo (PL) in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): RIGHT study.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA10502-LBA10502 ◽  
Author(s):  
Yoon-Koo Kang ◽  
Min-Hee Ryu ◽  
Baek-Yeol Ryoo ◽  
Hyun Jin Kim ◽  
Jong Jin Lee ◽  
...  
Keyword(s):  
Disease Control ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Advanced Gist

LBA10502 Background: To palliate and prolong disease control after failure of all available treatment in advanced GIST, resumption of IM dosing has been commonly practiced based on evidence of rapid GIST progression after discontinuation of all TKIs. We evaluated the efficacy of IM rechallenge in pts with advanced GIST following failure of all TKIs. Methods: Eligible pts had metastatic and/or unresectable GIST with prior benefit from first-line IM (defined as disease control for > 6 months), progressive disease (PD) on first-line IM, PD on or intolerance to SU, and ECOG performance status 0-3. Pts were randomized 1:1 to receive best supportive care with either IM 400 mg po once daily or PL. At the time of PD, pts were unblinded and allowed to cross-over to open-label IM. The primary endpoint was progression-free survival (PFS) determined by blinded external radiology review according to RECIST v1.0. Secondary endpoints included overall survival (OS), time to progression, disease control rate (DCR) at 12 weeks, and safety. Results: Between July 2010 and January 2013, 81 pts were randomized (IM: 41, PL: 40) at a single Korean center. All baseline characteristics were balanced between the arms and 40% of pts received ≥ 3 prior TKIs. The planned final analysis in March 2013 demonstrated that the primary endpoint was met, with significantly greater PFS for pts randomized to IM vs. PL : 1.8 vs. 0.9 months, respectively (p=0.002), hazard ratio (HR) 0.45 (95% CI, 0.27-0.76). DCR at 12 weeks was 32% for IM vs. 5% for PL (p=0.003). With 92.5 % of PL pts rapidly crossing over to IM, median OS was 8.2 months for IM vs. 7.5 months for PL (HR of 0.99, p=0.982). The most common treatment-emergent AEs (> grade 3) during double-blind period in the IM arm included anemia (29%), fatigue (10%), and hyperbilirubinemia (7%). Conclusions: Rechallenge of IM significantly improves PFS and DCR in pts with advanced GIST after failure of at least IM and SU, likely by continuous kinase inhibition of the bulk of disease clones which retain IM sensitivity. However, TKI-resistant clones continue to progress leading to relatively brief duration of benefit. Clinical trial information: NCT01151852.

Validation of the decipher genomic classifier (GC) in SAKK 09/10: A phase III randomized trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy (RP).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5010-5010
Author(s):  
Alan Dal Pra ◽  
Pirus Ghadjar ◽  
Stefanie Hayoz ◽  
Daniel Eidelberg Spratt ◽  
Vinnie YT Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Controlled Trial ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Phase Iii ◽  
Clinical Progression ◽  
Clinical Value ◽  
Prognostic Utility ◽  
The Impact

5010 Background: GC has been shown to independently prognosticate outcomes in prostate cancer. Herein, we validate the GC in a European randomized phase III trial of dose escalated SRT after RP. Methods: SAKK 09/10 (NCT01272050) randomized 350 patients with biochemical recurrence after RP to 64Gy vs 70Gy. No patients received androgen deprivation therapy (ADT) or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. RP samples were centrally reviewed for the highest-grade tumor and those passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to obtain the GC score (0 to 1; < 0.45, 0.45-0.6, > 0.6 for low-, intermediate-, and high, respectively). The primary aim of this study was to validate the GC for the prediction of freedom from biochemical progression (FFBP) using Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, PSA at randomization, and randomization arm. The secondary aims were to evaluate the association of GC with clinical progression-free survival (CPFS) and use of salvage ADT. Results: Of 233 patients with tissue available, 226 passed QC and were included for analysis. The final GC cohort was a representative sample of the overall cohort, with a median follow-up of 6.3 years (IQR 6.0-7.2). GC score (continuous per 0.1 unit, score 0-1) was independently associated with FFBP (HR 1.14 [95% CI 1.03-1.25], p = 0.009). Higher GC scores were independently associated with CPFS, use of salvage ADT, and rapid biochemical failure ( < 18 months after SRT). High- vs. low/intermediate-GC showed a HR of 2.22 ([95% CI 1.37-3.58], p = 0.001) for FFBP, 2.29 ([95% CI 1.32-3.98], p = 0.003) for CPFS, and 2.99 ([95% CI 1.50-5.95], p = 0.002) for use of salvage ADT. Patients with high-GC had 5-year FFBP of 45% [95% CI 32-59] vs 71% [95% CI 64-78] in low-intermediate GC. Similar estimates for GC risk groups were observed in the 64Gy vs 70Gy in GC high (5-year FFBP of 51% [95% CI 32-70] vs 39% [95% CI 20-59]) and in low-intermediate GC (75% [95% CI 65-84] vs 69% [95% CI 59-78]). Conclusions: This study represents the first contemporary randomized controlled trial in patients with recurrent prostate cancer treated with early SRT without ADT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and radiotherapy dose, patients with a high-GC were more than twice as likely than a lower GC score to experience biochemical and clinical progression and receive salvage ADT. This data confirms the clinical value of Decipher GC for tailoring treatment in the postoperative salvage setting.

Analysis of the effect of crossover from placebo (PBO) to darolutamide (DARO) on overall survival (OS) benefit in the ARAMIS Trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 240-240
Author(s):  
Neal D. Shore ◽  
Karim Fizazi ◽  
Teuvo Tammela ◽  
Murilo Luz ◽  
Manuel Philco Salas ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Safety Profile ◽  
Final Analysis ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Secondary Endpoints ◽  
The Impact

240 Background: DARO is a structurally distinct androgen receptor inhibitor approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) based on significantly prolonged metastasis-free survival compared with PBO (median 40.4 vs 18.4 months; hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.34–0.50; P < 0.0001) and a favorable safety profile in the phase III ARAMIS trial. Following unblinding at the primary analysis, crossover from PBO to DARO was permitted for the subsequent open-label treatment phase. Sensitivity analyses were performed to assess the effect of PBO–DARO crossover on OS benefit. Methods: Patients (pts) with nmCRPC receiving androgen deprivation therapy were randomized 2:1 to DARO (n = 955) or PBO (n = 554). In addition to OS, secondary endpoints included times to pain progression, first cytotoxic chemotherapy, first symptomatic skeletal event, and safety. The OS analysis was planned to occur after approximately 240 deaths, and secondary endpoints were evaluated in a hierarchical order. Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses were performed as pre-planned sensitivity analyses to adjust for the treatment effect of PBO–DARO crossover. The IPE method used a parametric model for the survival times and iteratively determined the model parameter describing the magnitude of the treatment effect, whereas a grid search and non-parametric log-rank test were used for the RPSFT analysis. The IPE and RPSFT analyses both generated a Kaplan–Meier curve for the PBO arm that predicts what would have been observed in the absence of PBO–DARO crossover. Results: After unblinding, 170 pts (30.7% of those randomized to PBO) crossed over from PBO to DARO; median treatment duration from unblinding to the final data cut-off was 11 months. Final analysis of the combined double-blind and open label periods was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts) and showed a statistically significant OS benefit for DARO vs PBO (HR 0.69; 95% CI 0.53–0.88; P = 0.003). Results from the IPE (HR 0.66; 95% CI 0.51–0.84; P < 0.001) and RPSFT (HR 0.68; 95% CI 0.51–0.90; P = 0.007) analyses were similar to those from the intention-to-treat population, showing that the impact of PBO–DARO crossover was small. Additional analyses accounting for the effect of PBO–DARO crossover will be presented. The safety profile of DARO continued to be favorable at the final analysis, and discontinuation rates at the end of the double-blind period remained unchanged from the primary analysis (8.9% with DARO and 8.7% with PBO). Conclusions: Early treatment with DARO in men with nmCRPC is associated with significant improvement in OS regardless of pts crossing over from PBO to DARO. The safety profile of DARO remained favorable at the final analysis. Clinical trial information: NCT02200614.

scholarly journals Oral levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

2019 ◽  
Vol 90 (10) ◽  
pp. 1165-1170 ◽  
Author(s):  
Ammar Al-Chalabi ◽  
Pamela Shaw ◽  
P Nigel Leigh ◽  
Leonard van den Berg ◽  
Orla Hardiman ◽  
...  
Keyword(s):  
Heart Rate ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Lateral Sclerosis

ObjectiveTo evaluate the efficacy and safety of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS). This phase II, randomised, double-blind, placebo-controlled, crossover, three-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60%–90 % of predicted from 11 sites in four countries.MethodsPatients received levosimendan 1 mg daily, 1 mg two times a day or placebo during three 14-day crossover periods and levosimendan 1–2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale-Revised (ALSFRS-R), tolerability and safety.ResultsOf 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being −3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg two times a day (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg two times a day (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events.ConclusionsLevosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase III study to evaluate the longer term effects of oral levosimendan in ALS is ongoing.

scholarly journals Perioperative rifaximin is not associated with enhanced functional and volumetric recovery after major liver resection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jan Bednarsch ◽  
Zoltan Czigany ◽  
Sven H. Loosen ◽  
Lara Heij ◽  
Lorenz Ruckgaber ◽  
...  
Keyword(s):  
Liver Function ◽  
Primary Endpoint ◽  
Major Hepatectomy ◽  
Controlled Trial ◽  
Liver Volume ◽  
Relative Increase ◽  
Control Group ◽  
Open Label ◽  
Significant Difference ◽  
The Impact

AbstractThe objective of this randomized controlled trial (RCT) was to assess the impact of rifaximin on the course of liver function, liver regeneration and volumetric recovery in patients undergoing major hepatectomy. The ARROW trial was an investigator initiated, single-center, open-label, phase 3 RCT with two parallel treatment groups, conducted at our hepatobiliary center from 03/2016 to 07/2020. Patients undergoing major hepatectomy were eligible and randomly assigned 1:1 to receive oral rifaximin (550 mg twice daily for 7–10 or 14–21 days in case of portal vein embolization preoperatively and 7 days postoperatively) versus no intervention. Primary endpoint was the relative increase in postoperative liver function measured by LiMAx from postoperative day (POD) 4 to 7. Secondary endpoint were the course of liver function and liver volume during the study period as well as postoperative morbidity and mortality. Between 2016 and 2020, 45 patients were randomized and 35 patients (16 individuals in the rifaximin and 19 individuals in the control group) were eligible for per-protocol analysis. The study was prematurely terminated following interim analysis, due to the unlikelihood of reaching a significant primary endpoint. The median relative increase in liver function from POD 4 to POD 7 was 27% in the rifaximin group and 41% in the control group (p = 0.399). Further, no significant difference was found in terms of any other endpoints of functional liver- and volume regeneration or perioperative surgical complications following the application of rifaximin versus no intervention. Perioperative application of rifaximin has no effect on functional or volumetric regeneration after major hepatectomy (NCT02555293; EudraCT 2013-004644-28).

scholarly journals Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial

2020 ◽  
pp. annrheumdis-2020-218599
Author(s):  
Alan N Baer ◽  
Jacques-Eric Gottenberg ◽  
E William St Clair ◽  
Takayuki Sumida ◽  
Tsutomu Takeuchi ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Controlled Trial ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Patient Reported ◽  
Sjögren‘S Syndrome

ObjectivesTo evaluate efficacy and safety of abatacept in adults with active primary Sjögren’s syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial.MethodsEligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored.ResultsOf 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI −3.2 abatacept vs −3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified.ConclusionsAbatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.

Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study

2007 ◽  
Vol 25 (30) ◽  
pp. 4779-4786 ◽  
Author(s):  
Charles S. Fuchs ◽  
John Marshall ◽  
Edith Mitchell ◽  
Rafal Wierzbicki ◽  
Vinod Ganju ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Study ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
First Line Treatment

PurposeThis phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).Patients and MethodsA total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.ResultsMedian PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of ≥ grade 3 hypertension than mIFL+Bev.ConclusionFOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.

SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8001-8001 ◽  
Author(s):  
F. Cappuzzo ◽  
T. Ciuleanu ◽  
L. Stelmakh ◽  
S. Cicenas ◽  
A. Szczesna ◽  
...  
Keyword(s):  
Disease Control ◽  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Double Blind ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8001 Background: Erlotinib (E), a small-molecule EGFR TKI, is proven to extend survival versus placebo (P) in 2nd/3rd-line advanced NSCLC. The phase III SATURN study (BO18192) was initiated to evaluate E as maintenance therapy after standard 1st-line platinum-based chemotherapy (CT) in advanced NSCLC. Methods: Patients with no evidence of disease progression after 4 cycles of CT were randomized to receive either E 150 mg/day or P until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) in all patients and the co-primary endpoint was PFS in EGFR immunohistochemistry-positive (IHC+) patients. Results: A total of 1,949 patients entered the CT phase, of whom 889 were randomized to E (n=438) or P (n=451). Median age was 60 years for both arms. Baseline characteristics for E and P arms (%): male/female: 73/27 and 75/25; adenocarcinoma + BAC/squamous-cell/other: 47/38/15 and 44/43/13; stage IIIB/IV: 26/74 and 24/76; Caucasian/Asian/other: 84/14/2 and 83/15/2; ECOG PS 0/1: 31/69 and 32/68; current/former/never smoker: 55/28/18 and 56/27/17. PFS (by investigator assessment; confirmed by independent review) was significantly prolonged with E versus P in all patients (HR 0.71 [95% CI 0.62–0.82]; p<.0001) and in EGFR IHC+ patients (HR 0.69 [95% CI 0.58–0.82]; p<.0001). Subgroup analyses will be reported. Response rate was 12% with E versus 5% with P. Disease control rate (complete response + partial response + stable disease >12 wks) was 40.8% with E versus 27.4% with P (p<.0001). OS data are not yet mature. E was well tolerated: the majority of treatment-related adverse events (AEs) were grade 1/2. AEs reported in ≥10% of all patients were rash (60% with E versus 9% with P) and diarrhea (20% with E versus 5% with P); again, most were grade 1/2. Only 2.3% of patients receiving E had a serious treatment-related AE and 2.8% withdrew due to a treatment-related AE. Conclusions: The SATURN study met its primary and co-primary endpoints with high statistical significance. Erlotinib in the 1st-line maintenance setting is well tolerated, and significantly improves disease control and delays progression versus placebo across patient subgroups. [Table: see text]

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

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