RECORD-4 phase 2 trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC): Final OS analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 560-560
Author(s):  
Thomas Cosgriff ◽  
Lin Yang ◽  
Anna Alyasova ◽  
Dingwei Ye ◽  
Andrey Karpenko ◽  
...  
Keyword(s):  
Disease Progression ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Second Line ◽  
Phase 2 ◽  
First Line ◽  
Primary Analysis ◽  
First Line Therapy ◽  
Phase 2 Trial ◽  
Anti Vegf

560 Background: The phase 2 RECORD-4 study assessed EVE in pts with mRCC who progressed after 1 prior anti-VEGF or cytokine (J Clin Oncol 2015;abstr 4518). At primary analysis, median progression-free survival (PFS, primary end point) in the overall population was 7.8 months (95% CI, 5.7-11.0). Here we present results of the final updated primary PFS and final overall survival (OS) analysis. Methods: RECORD-4 enrolled 134 pts with clear cell mRCC into 1 of 3 cohorts based on prior first-line therapy: sunitinib (cohort 1, n=58), other anti-VEGF (cohort 2, n=62: 23 sorafenib, 16 bevacizumab, 13 pazopanib, 10 other), or cytokines (cohort 3, n=14). Pts received EVE 10 mg/d until progression of disease (PD; RECIST, v1.0) or intolerance. Database lock for final analysis was June 26, 2015. Results: Demographics were balanced among cohorts; overall most pts were men (68%) and most had good/intermediate MSKCC prognosis (90%); median age was 59 yrs. Median duration of exposure was 5.8 mo. At the time of final analysis, study discontinuation was primarily due to disease progression (61%). In the overall population, median PFS (95% CI) was 7.4 (5.6-10.5) mo and median OS (95% CI) was 23.8 (17.0-not evaluable [NE]) mo (Table). Overall rate of grade 3 or 4 adverse events (AEs) was 56%. There were 13 on-treatment deaths; primary causes were disease progression, multi-organ failure, and respiratory failure (2.3% each). Conclusions: RECORD-4 final OS analysis supports EVE as a second-line option after sunitinib and other first-line therapies. EVE safety profile was consistent with previous experience. Clinical trial information: NCT01491672. [Table: see text]

Phase I/II study of ramucirumab plus nivolumab in patients in second-line treatment for advanced gastric adenocarcinoma (NivoRam study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 129-129 ◽  
Author(s):  
Hiroki Hara ◽  
Hirokazu Shoji ◽  
Daisuke Takahari ◽  
Taito Esaki ◽  
Nozomu Machida ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Second Line ◽  
Phase 2 ◽  
Primary Analysis ◽  
Secondary Endpoints ◽  
Advanced Gastric Adenocarcinoma ◽  
Grade 3 ◽  
Line Chemotherapy

129 Background: Nivolumab (Nivo) showed a survival benefit in salvage line of advanced gastric cancer (AGC) patients in ATTRACTION-2 trial. Based on synergistic anti-tumor effects by simultaneous blockade of PD-1 and VEGFR-2, this phase 1/2 study was conducted to investigate the safety and efficacy of Nivo plus ramucirumab (Ram) in the second line chemotherapy for AGC. Methods: AGC patients with measurable lesions, PS 0-1, disease progression on first line chemotherapy containing platinum were eligible. Patients received Nivo (3mg/kg, Q2W) and Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. After feasibility was evaluated in six patients (phase 1 part), additional 40 patients were required in a phase 2 part with the primary analysis (expected 6-months progression-free survival (PFS) rate of 36%, threshold of 18%, one-sided alpha level of 10%, power of 90%). Secondary endpoints included overall response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and safety. Results: 46 AGC patients (median age 66 years, PS 1 40%) were enrolled. No dose limiting toxicities were observed in the phase 1 part. With median follow up time of 10.2 month, 6-month PFS rate was 37.4% (90% confidential intervals: 25.7-49.2%), which met the primary endpoint of the phase 2 part. ORR/DCR were 26.7%/62.2%. Median PFS/OS were 2.9/9.0 months. Among all enrolled patients, grade 3 or 4 treatment related adverse events were hypertension (n = 2), diarrhea (n = 2), perforation at jejunum (n = 1), hemorrhage (n = 1), colitis (n = 1), pancreatitis (n = 1), liver dysfunction (n = 1), cholangitis (n = 1), hematoma (n = 1), neutropenia (n = 1) and proteinuria (n = 1). There were no treatment-related deaths. Conclusions: Combination of Nivo and Ram showed promising antitumor activity and mild toxicity profile for second line AGC, which is worth evaluating in a further confirmatory study. Clinical trial information: NCT02999295.

Anti-VEGF and anti-EGFR monoclonal antibodies (Mabs) in the first-line therapy for metastatic colorectal cancer: A meta-analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15012-e15012
Author(s):  
Z. Zhou ◽  
W. V. Walsh ◽  
V. G. Bathini ◽  
B. Piperdi
Keyword(s):  
Disease Progression ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Anti Vegf ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Ras Status

e15012 Background: Anti-VEGF (VEGFi) and anti-EGFR (EGFRi) Mabs have increased options for patients with metastatic colorectal cancers (mCRC). The optimal class of antibody to combine with chemotherapy (Ctx) in the first-line treatment for mCRC remains less well defined. Results from randomized controlled trials (RCTs) are variable. Methods: Systematic review and meta-analysis were performed on the basis of previously released RCTs results. We searched the MEDLINE, Cochrane registry, proceedings from ASCO, ECCO, ESMO until 12/ 2008 for RCTs of Mabs in first-line mCRC. Summary statistics were pooled hazard ratio (HR) of progression-free survival (PFS), overall survival (OS) and odds ratio (OR) of Response rate (RR) and 60 day mortality (60d-M). Effect of k-ras wild type and mutation were stratified in trials involving EGFRi. Results: 7 trials with complete data were identified, including 3 Ctx ± VEGFi (AVF2107g, NO16966, JCO2005.05.122), n=2422; 2 Ctx±EGFRi (CRYSTAL, OPUS), n=1554; 2 Ctx/VEGFi ± EGFRi (PACCE, CAIRO-2), n=1789. Addition of VEGFi to Ctx offered 20–30% risk reduction in disease progression and overall mortality, a 30% higher RR and nonsignificant 60d-M. Benefit of EGFRi in addition to Ctx was seen only in k-ras wild type patients with 36% reduction in disease progression and doubling in RR. However, addition of EGFRi to Ctx+VEGFi caused increased risk of progression and death with no significant increase in RR and 60d-M. Conclusions: Benefit of VEGFi in addition to Ctx in first-line mCRC is well pronounced and persistent. In k-ras wild type patients, addition of EGFRi to Ctx results in significant increase in RR and PFS. Addition of EGFRi to Ctx+VEGFi appeared harmful regardless of k- ras status. [Table: see text] [Table: see text]

Exploratory biomarker findings from cohort 2 of MODUL: An adaptable, phase 2, signal-seeking trial of fluoropyrimidine + bevacizumab ± atezolizumab maintenance therapy for BRAFwt metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3570-3570
Author(s):  
Josep Tabernero ◽  
Axel Grothey ◽  
Dirk Arnold ◽  
Michel Ducreux ◽  
Peter J. O'Dwyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
Predictive Biomarkers ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Phase 2 ◽  
First Line ◽  
Tissue Samples ◽  
First Line Therapy

3570 Background: MODUL is an adaptable, phase 2, signal-seeking trial testing novel agents as first-line therapy for predefined subgroups of patients with metastatic colorectal cancer (mCRC). Previously reported findings demonstrated that adding atezolizumab to fluoropyrimidine (FP)/bevacizumab as first-line maintenance treatment after induction with FOLFOX + bevacizumab did not improve efficacy outcomes in BRAFwt mCRC. Given these efficacy results, exploratory assessments on tumour samples were conducted to provide insights into factors that might affect efficacy of maintenance treatment and provide guidance on appropriate therapeutic strategies for BRAFwt mCRC. Methods: In patients with BRAFwt tumours (Cohort 2), experimental treatment was FP/bevacizumab + atezolizumab. Primary efficacy endpoint: progression-free survival (PFS). Overall survival (OS) was a secondary endpoint. Archival tissue samples from 104 patients were analysed by immunohistochemistry (IHC) at HistoGeneX (PD-L1; CD8/GrB/FoxP3). SP142 antibody was used for PD-L1 IHC analysis, which evaluated PD-L1low (IC 0–1) vs PD-L1high (IC > 1) in correlation with PFS and OS in the control and experimental arms. CD8/GrB/FoxP3 triplex staining was also performed to evaluate potential correlations with efficacy. Results: 445 patients with BRAFwt mCRC were randomised (2:1 ratio) to maintenance treatment in Cohort 2. Archival samples from 104 patients were analysed: FP/bevacizumab + atezolizumab (n = 82); FP/bevacizumab (n = 22). The biomarker evaluable population (BEP) for PD-L1 was n = 81 for FP/bevacizumab + atezolizumab [PD-L1low n = 35 (43%); PD-L1high n = 46 (57%)] and n = 22 for FP/bevacizumab [PD-L1low n = 16 (72%); PD-L1high n = 6 (28%)]. The BEP for CD8/GrB was n = 50 for FP/bevacizumab + atezolizumab and n = 16 for FP/bevacizumab. No difference in PFS or OS was observed in the FP/bevacizumab + atezolizumab vs FP/bevacizumab arms for PD-L1high [PFS: HR = 1.5 (95% CI 0.45−4.8), p = 0.51; OS: HR = 1.3 (95% CI 0.38−4.1), p = 0.71] or PD-L1low [PFS: HR = 0.92 (95% CI 0.47−1.8), p = 0.81; OS: HR = 0.78 (95% CI 0.4−1.5), p = 0.48]. Similar results were observed with CD8/GrBhigh [PFS: HR = 0.73 (95% CI 0.27−2.0), p = 0.55; OS: HR = 0.66 (95% CI 0.24−1.8), p = 0.44], CD8/GrBlow [PFS: HR = 1.0 (95% CI 0.42–2.5), p = 0.96; OS: HR = 0.73 (95% CI 0.3–1.8), p = 0.5], FoxP3high [PFS: HR = 0.97 (95% CI 0.37−2.5), p = 0.95; OS: HR = 0.95 (95% CI 0.36−2.5), p = 0.91] and FoxP3low [PFS: HR = 0.73 (95% CI 0.29−1.9), p = 0.53; OS: HR = 0.5 (95% CI 0.19−1.3), p = 0.18]. Conclusions: These findings suggest that PD-L1, CD8/GrB and FoxP3 might not be predictive biomarkers in BRAFwt mCRC. Further analyses are needed to further evaluate potential predictive and prognostic factors of response in this setting. Clinical trial information: NCT02291289.

scholarly journals Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

scholarly journals Phase II Randomized Trial Comparing Sequential First-Line Everolimus and Second-Line Sunitinib Versus First-Line Sunitinib and Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma

2014 ◽  
Vol 32 (25) ◽  
pp. 2765-2772 ◽  
Author(s):  
Robert J. Motzer ◽  
Carlos H. Barrios ◽  
Tae Min Kim ◽  
Silvia Falcon ◽  
Thomas Cosgriff ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Second Line ◽  
First Line ◽  
First Line Therapy

Purpose A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma. Patients and Methods RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety. Results Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively). Conclusion Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

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]

Final analysis of the phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with chemotherapy refractory, K-RAS wild-type (WT), metastatic colorectal carcinoma (mCRC): The NCIC Clinical Trials Group and AGITG CO.20 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3504-3504 ◽  
Author(s):  
Lillian L. Siu ◽  
Jeremy David Shapiro ◽  
Derek J. Jonker ◽  
Christos Stelios Karapetis ◽  
John Raymond Zalcberg ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Primary Analysis ◽  
Positive Effects ◽  
Anti Vegf ◽  
Global Quality ◽  
Global Quality Of Life ◽  
Subgroup Analyses

3504 Background: The anti-EGFR monoclonal antibody CET has improved survival in pts with chemotherapy refractory, K-RAS WT mCRC. BRIV is a potent inhibitor of multiple receptor tyrosine kinases including both VEGFR and FGFR. The combination of CET and BRIV targets tumor growth and angiogenesis and demonstrated encouraging activity in an early phase clinical trial. Methods: Pts with mCRC previously treated with combination chemotherapy were randomized 1:1 to receive CET 400 mg/m2 IV loading dose followed by weekly maintenance of 250 mg/m2 plus either BRIV 800 mg PO daily (Arm A) or placebo (Arm B). Pts may have had 1 prior anti-VEGF, but no prior anti-EGFR therapy. Primary endpoint was overall survival (OS). Results: From 02/2008 to 02/2011, 750 pts were randomized (376 in Arm A and 374 in Arm B). Demographics: median age=64 (range 27-88); male=64%; ECOG 0:1:2 (%)=32:58:10; >3 prior chemotherapy regimens=92%; prior anti-VEGF therapy=41%; K-RAS WT=97%. Primary analysis was conducted per protocol after 536 deaths were observed, with median OS of 8.8 months in Arm A and 8.1 months in Arm B, hazard ratio (HR)=0.88; 95% CI=0.74 to 1.03; p=0.12. Median progression-free survival (PFS) was 5.0 months in Arm A and 3.4 months in Arm B, HR=0.72; 95% CI=0.62 to 0.84; p<0.0001. Incidence of any ≥grade 3 adverse event (AE) was 78% in Arm A and 53% in Arm B. Time to deterioration of physical function was shorter and global quality of life scores were lower in Arm A vs Arm B. Planned subgroup analyses revealed no statistically difference in treatment effects on OS based on pre-specified factors of age, gender, ECOG and race. Likewise, no difference was detected based on exploratory subgroup analyses of LDH and prior anti-VEGF therapy. Conclusions: Despite positive effects on PFS, the combination of CET+BRIV did not significantly improve OS in pts with chemotherapy refractory, K-RAS WT mCRC. Final updated results based on 20-25% additional events for a total of nearly 700 deaths, as well as further exploratory subgroup analyses, will be presented.

Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 641-641
Author(s):  
Kiyoshi Ishigure ◽  
Goro Nakayama ◽  
Keisuke Uehara ◽  
Hiroyuki Yokoyama ◽  
Akiharu Ishiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bleeding Event ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
To Receive

641 Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients. Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety. Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy. Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.

EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (RCC) (ANZUP trial 0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4681-TPS4681 ◽  
Author(s):  
Ian D. Davis ◽  
Val Gebski ◽  
Mark D. Chatfield ◽  
Peter S. Grimison ◽  
George Kannourakis ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Prognostic Score ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).

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