Gastrointestinale Stromatumoren: Regorafenib als Drittlinientherapie erfolgreich

2012 ◽  
Vol 03 (04) ◽  
pp. 200-200
Author(s):  
Birgit Pohlmann
Keyword(s):  
Phase Iii ◽  
Gastrointestinale Stromatumoren ◽  
Multikinase Inhibitor

Eine potenzielle neue Standardtherapie für Patienten mit metastasiertem bzw. inoperablem GIST nach Imatinib-und Sunitinib-Versagen sieht Prof. Carsten Bokemeyer, Hamburg, in dem oralen Multikinase-Inhibitor Regorafenib. In der randomisierten Phase-III-Studie GRID wurde Regorafenib als Drittlinientherapie nach Imatinib- und Sunitinib-Versagen gegen best-supportiv-care verglichen und erreichte eine statistisch hoch signifikante Verlängerung der PFS, dem primären Studienendpunkt (4,8 vs. 0,9 Monaten; HR 0,27; p˂0,0001).

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.

Regorafenib (REG) in progressive metastatic colorectal cancer (mCRC): Analysis of age subgroups in the phase III CORRECT trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3636-3636 ◽  
Author(s):  
Eric van Cutsem ◽  
Alberto Sobrero ◽  
Salvatore Siena ◽  
Alfredo Falcone ◽  
Marc Ychou ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Correct Trial ◽  
Multikinase Inhibitor ◽  
Once Daily ◽  
Grade 3 ◽  
Dose Modifications ◽  
The Impact ◽  
To Receive

3636 Background: In the CORRECT phase III trial, the multikinase inhibitor REG demonstrated significant improvement in overall survival (OS) and progression-free survival vs placebo (Pla) in patients (pts) with mCRC whose disease progressed on other standard therapies. The most frequent REG-related grade ≥3 adverse events (AEs) of interest were hand–foot skin reaction (HFSR), fatigue, diarrhea, hypertension, and rash/desquamation. We explored whether the impact of REG in pts aged ≥65 years differed from that in younger patients. Methods: Pts with mCRC progressing following all other available therapies were randomized 2:1 to receive REG 160 mg once daily (n=505) or Pla (n=255) for the first 3 weeks of each 4-week cycle. The dose could be modified to manage AEs. The primary endpoint was OS. We report efficacy, safety, and dosing data from REG recipients by age. Results: The REG treatment group included 309 pts <65 years (307 evaluable for safety) and 196 pts ≥65 years (193 evaluable for safety). The OS hazard ratio (REG/Pla) was 0.72 (95% confidence interval [CI] 0.56–0.91) in pts <65 years and 0.86 (95% CI 0.61–1.19) in pts ≥65 years (interaction p-value = 0.405). Median OS was 6.7 vs 5 months for REG vs Pla in pts <65 years, and 6.0 vs 5.6 months, respectively, in pts ≥65 years. Most pts experienced drug-related AEs (<65 years: 93.8%; ≥65 years: 91.7%). The rates of grade ≥3 REG-related AEs of interest and dose modifications are shown in the Table. In pts <65 years vs ≥65 years, median (interquartile range [IQR]) duration of REG was 7.6 weeks (6.6–15.4) vs 7.1 weeks (5.1–17.2), median (IQR) daily REG dose was 160.0 mg (134.6–160.0) vs 160.0 mg (137.5–160.0), and median (IQR) proportion of planned REG dose was 83.3% (65.7–100.0) vs 78.6% (66.7–100.0), respectively. Conclusions: In the CORRECT trial, REG demonstrated an OS benefit in pts <65 years and ≥65 years. Safety and tolerability of REG appeared to be similar in both age subgroups. Clinical trial information: NCT01103323. [Table: see text]

Phase II trial of temsirolimus (TEM) plus sorafenib (SOR) in hepatocellular carcinoma (HCC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS501-TPS501
Author(s):  
Robin Kate Kelley ◽  
Halla Sayed Nimeiri ◽  
John Dozier Gordan ◽  
Jimmy Hwang ◽  
Ryan M. McWhirter ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Mtor Pathway ◽  
Micro Rna ◽  
Phase Iii ◽  
Virus Reactivation ◽  
Multikinase Inhibitor ◽  
Mtor Inhibition ◽  
Oncology Research

TPS501 Background: The multikinase inhibitor SOR prolongs survival in patients with HCC not amenable to curative therapies. In HCC preclinical models, the combination of SOR with an inhibitor of the mammalian target of rapamycin (mTOR) pathway is synergistic, though single-agent mTOR inhibition did not improve survival in HCC patients after failure of SOR in a phase III trial. We previously completed a phase I study of the mTOR inhibitor TEM combined with SOR in 25 HCC patients which identified the maximum tolerated dose as TEM 10 mg IV weekly and SOR 200 mg PO BID. This two-center, phase II study was developed to examine the efficacy of the combination and to explore candidate biomarkers. The study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support, with activation October 2012. Methods: The study is registered on ClinicalTrials.gov (NCT01687673). Design: Single-arm, one stage phase II trial. Primary endpoint: Time to progression (TTP) by RECIST 1.1. Other endpoints: Progression-free survival, response rate, overall survival, proportion with alpha fetoprotein decline ≥ 50%, toxicity, hepatitis B virus reactivation rate, and exploratory biomarkers including mTOR pathway protein expression in tumor, circulating tumor cells, and blood and tumor micro-RNA profiles. Sample size: 25 evaluable patients are required to detect a difference between the null hypothesis of median TTP < 3 months versus alternate hypothesis of median TTP ≥ 6 months (a clinically-meaningful outcome in advanced HCC), with 1-sided significance level of 10% and power 88% under the exact test. Main eligibility criteria: HCC not amenable to curative therapies, histologically-confirmed, ≥ 1 untreated, radiographically-measurable site of disease. No prior systemic therapy. ECOG ≤ 1. Child-Pugh score ≤ 7 with bilirubin ≤ 2 mg/dL. Treatment and procedures: TEM 10 mg IVweekly plus SOR 200 mg PO BID in 28-day cycles, with collection of archival tumor samples and blood samples at baseline, on treatment, and at progression. Accrual:Sixteen of 25 planned evaluable patients have enrolled. An interim analysis for safety after 30% enrollment met pre-specified target to continue. Clinical trial information: NCT01687673.

Phase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6589-TPS6589 ◽  
Author(s):  
Lillian L. Siu ◽  
Barbara Burtness ◽  
Ezra E.W. Cohen ◽  
Kevin Joseph Harrington ◽  
Lisa F. Licitra ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Imaging ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor ◽  
End Points

TPS6589 Background: The PD-1 inhibitor pembrolizumab is currently approved as first-line monotherapy for patients with R/M HNSCC whose tumors express PD-L1 combined positive score (CPS) ≥1. In a phase 1b/2 trial (NCT02501096) of pembrolizumab plus lenvatinib (multikinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRa, RET, and KIT) in solid tumors, the combination demonstrated promising antitumor activity and a manageable safety profile in patients with HNSCC. LEAP-010 (NCT04199104) is a randomized, double-blind, placebo-controlled, phase 3 study that will evaluate the efficacy and safety of first-line pembrolizumab with or without lenvatinib in patients with PD-L1–positive R/M HNSCC. Methods: Key eligibility criteria include histologically confirmed R/M HNSCC incurable by local therapies, PD-L1–positive tumor (CPS ≥1) as determined by central laboratory, measurable disease as assessed by blinded independent central review (BICR) per RECIST v1.1, and ECOG performance status (PS) 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab plus lenvatinib or pembrolizumab plus placebo. Randomization will be stratified by PD-L1 status defined by tumor proportion score ( < 50% vs ≥50%), human papillomavirus status for oropharynx cancer (positive vs negative), and ECOG PS (0 or 1). Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles (~2 years) and oral lenvatinib 20 mg or placebo once daily; patients may continue to receive lenvatinib or placebo after pembrolizumab treatment is complete. Treatment will continue until BICR-verified disease progression or unacceptable toxicity. Pembrolizumab retreatment (second course) for 17 additional cycles will be allowed for eligible patients who stop pembrolizumab and subsequently experience BICR-verified disease progression. These patients could have stopped treatment with stable disease, partial response, or complete response or after 35 cycles of pembrolizumab for reasons other than disease progression or toxicity. Tumor imaging assessment will be performed at week 6, then every 6 weeks until 1 year, and thereafter every 9 weeks. Primary end points are objective response rate and progression-free survival, assessed by BICR per RECIST v1.1, and overall survival. Secondary end points are duration of response and safety and tolerability. Recruitment is ongoing; planned enrollment is ~500 patients. Clinical trial information: NCT04199104 .

Use of phosphoprotein profiling with high-density fluorescence protein microarray to reveal a response predictor to a multikinase inhibitor sorafenib.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15080-e15080
Author(s):  
Tesshi Yamada ◽  
Mari Masuda ◽  
Wei-Yu Chen ◽  
Chi-Long Chen ◽  
Kazufumi Honda
Keyword(s):  
Cell Lines ◽  
Protein Microarray ◽  
Mammalian Target Of Rapamycin ◽  
Mapk Signaling ◽  
High Density ◽  
Mitogen Activated Protein Kinase ◽  
Phase Iii ◽  
Multikinase Inhibitor ◽  
Targeting Therapy ◽  
Hcc Cells

e15080 Background: The efficacy of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) has been revealed in the recent phase III SHARP (Sorafenib HCC Assessment Randomized Protocol) clinical trial, but only a small proportion of patients achieved the anticipated therapeutic outcomes. It is essential to identify biomarkers that will discriminate such patients. Methods: We newly developed high-density fluorescence reverse-phase protein arrays and used them to profile the phosphorylation status of 180 signaling molecules in the 120 pathways registered on the NCI-Nature curated database in 23 HCC cell lines with different sensitivities to sorafenib. Results: Among the 180 signaling nodes, we found that the level of ribosomal protein S6 phosphorylated at serine residues 235/236 (p-rpS6 S235/236) was the most significantly correlated with the sensitivity of HCC cells to sorafenib. The high expression of p-rpS6 S235/236 was confirmed immunohistochemically in biopsy samples obtained from HCC patients who responded poorly to sorafenib. Sorafenib-resistant HCC cells showed constitutive activation of the mammalian target of rapamycin (mTOR) and/or the mitogen-activated protein kinase (MAPK) pathways downstream of c-RAF. Conclusions: The present results indicate that p-rpS6 S235/236 is a potential predictor of unresponsiveness to sorafenib. Cross-talk between the mTOR and MAPK signaling pathways in sorafenib-resistant HCC cell lines was also revealed. A combination of mTOR and MAPK inhibitors may improve the efficacy of molecular targeting therapy against HCC.

Effects of regorafenib therapy on health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) in the phase III CONCUR trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 697-697 ◽  
Author(s):  
Shukui Qin ◽  
Tae Won Kim ◽  
Thomas Cheung Yau ◽  
Brigette Ma ◽  
Hongming Pan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Life Questionnaire ◽  
Multikinase Inhibitor ◽  
Entire Treatment Period ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Mean Time

697 Background: The CONCUR trial (NCT01584830) showed that the multikinase inhibitor regorafenib (REG) significantly improved overall survival and progression-free survival vsplacebo (PBO) in Asian patients with mCRC who had progressed on approved standard therapies. HRQoL was an exploratory endpoint. Methods: In this international multicenter trial conducted in Asia, patients were randomized 2:1 to receive REG 160 mg (n=136) or PBO (n=68) once daily for the first 3 weeks of each 4-week cycle. Prespecified QoL analyses were conducted on all 204 patients using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol-five dimension questionnaire (EQ-5D). HRQoL outcomes were expressed as time-adjusted area under the curve (AUC) to allow descriptive evaluations of QoL in the REG and PBO groups across the entire treatment period. Individual domains were also compared using descriptive statistics. Results: Overall, changes in HRQoL were similar in the REG and PBO groups. Difference in least-squares (LS) mean time-adjusted AUC of the EORTC QLQ-C30 global health status/QoL (GH) score: −0.40 (95% CI: −3.53 to 2.72); differences in LS mean time-adjusted AUC for EQ-5D index and visual analog scale (VAS) scores: −0.03 (95% CI: −0.08 to 0.01) and −1.18 (95% CI: −4.01 to 1.66), respectively. The PBO group had <5 patients after cycle 3, so results should be interpreted with caution. Changes from baseline scores in cycles 2 and 3 did not appear to differ between REG and PBO on the 15 domains of the EORTC QLQ-C30, the EQ-5D index, and the VAS. Conclusions: No substantial differences in overall changes in HRQoL were seen between patients treated with REG and PBO in the CONCUR trial. Clinical trial information: NCT01584830. [Table: see text]

Lenvatinib – A multikinase inhibitor for radioiodine-refractory differentiated thyroid cancer

2016 ◽  
Vol 24 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Yvonne Hewett ◽  
Subash Ghimire ◽  
Bilal Farooqi ◽  
Binay K Shah
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Multikinase Inhibitor ◽  
The Us ◽  
Phase Iii Study ◽  
New Treatment

Lenvatinib, an oral multikinase inhibitor, was approved by the US Food and Drug Administration in February 2015. In a pivotal phase III study of 392 patients with progressive radioiodine-refractory thyroid cancer, the overall response rate of patients receiving lenvatinib was 64.8%, with complete response in four patients. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in patients receiving placebo. Median overall survival was not reached in either arm. Lenvatinib is a promising new treatment for patients with radioiodine (iodine-131)-refractory differentiated thyroid cancer.

scholarly journals Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the CORRECT trial who had progression-free survival (PFS) longer than 4 months.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 710-710 ◽  
Author(s):  
Axel Grothey ◽  
Alfredo Falcone ◽  
Yves Humblet ◽  
Olivier Bouche ◽  
Laurent Mineur ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Real Life ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Correct Trial ◽  
Multikinase Inhibitor ◽  
Biomarker Analysis ◽  
Common Grade ◽  
Grade 3 ◽  
Post Hoc

710 Background: In the CORRECT phase III trial (NCT01103323), the multikinase inhibitor REG significantly improved overall survival (OS) and PFS vs placebo in patients with mCRC who had disease progression after other standard therapies (HR for OS: 0.77; 1-sided p =0.0052; Grothey 2013). A post-hoc exploratory subgroup analysis was conducted to evaluate patients in the REG treatment group who had a PFS longer than 4 months (long-PFS) defined as patients who progressed, died, or discontinued treatment for other reasons after 4 months. Methods: Of the505 patients randomized to REG in CORRECT, 98 (19.4%) were classified as having a long-PFS benefit. Baseline characteristics, safety, and dosing parameters were analyzed descriptively. Results: The long-PFS subpopulation was representative of the overall study population (Table). Long-PFS patients received a median of 6 cycles of REG (1-12), 92% received ≥5 cycles, and 20% had > 8 cycles. Overall 34% of patients had dose reductions and 87% had dose interruptions. The actual mean daily dose was 139 mg and the mean percent of the planned dose was 81%. Adverse events (AE) of any grade were experienced by all long-PFS patients, and the most common grade ≥3 AEs were hand-foot skin reaction (20%), hypertension (17%), diarrhea (17%), and fatigue (16%). Conclusions: A subset of 98 (19.4%) patients treated with REG in the CORRECT study had a PFS > 4 months, confirming the clinical benefit and tolerability of REG as a treatment option for patients with mCRC. Prospective validation of these findings in conjunction with biomarker analysis from real-life clinical experience is needed. Clinical trial information: NCT01103323. [Table: see text]

Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA5503-LBA5503 ◽  
Author(s):  
Andreas Du Bois ◽  
Anne Floquet ◽  
Jae Weon Kim ◽  
Jörn Rau ◽  
Jose Maria Del Campo ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Primary Analysis ◽  
Double Blind ◽  
Multikinase Inhibitor ◽  
Peritoneal Cancer ◽  
Line Chemotherapy

LBA5503 Background: Pazopanib is an oral, multikinase inhibitor of VEGFR-1, -2, -3, PDGFR-α and -β, and c-Kit. Preclinical and clinical studies support VEGF(R) and PDGF(R) as targets for AEOC treatment. This study evaluated the efficacy, safety, and tolerability of pazopanib maintenance therapy in patients who have not progressed after first-line chemotherapy for AEOC. Methods: Patients with histologically confirmed AEOC, FIGO II-IV, and no evidence of progression after surgery and ≥ 5 cycles of platinum-taxane chemotherapy were randomized 1:1 to receive 800 mg pazopanib once daily or placebo for up to 24 months. Primary endpoint was progression-free survival (PFS) by RECIST. Secondary endpoints included overall survival, PFS by GCIG criteria, safety, and quality of life. Results: Most of the 940 randomized patients had stage III/IV disease (91%) at initial diagnosis, and no residual disease after surgery (58%). The median time from diagnosis to randomization was 7.1 months in the placebo arm and 7.0 months in the pazopanib arm. The median follow-up was 24 months. Patients in the pazopanib arm had a prolonged PFS vs placebo (HR = 0.766; 95% CI: 0.64-0.91; p = 0.0021; medians 17.9 vs 12.3 months, respectively). Sensitivity and subgroup analyses of PFS, and analysis of PFS by GCIG criteria, were consistent with the primary analysis. The first interim analysis for OS (only 189 OS events = 20.1% of population) showed no difference between arms. Pazopanib mean exposure was shorter vs placebo (8.9 vs 11.7 months). Pazopanib treatment was associated with a higher incidence of adverse events (AEs) and serious AEs (26% vs 11%) vs placebo. The most common AEs were hypertension, diarrhea, nausea, headache, fatigue, and neutropenia. Fatal SAEs were reported in three patients on pazopanib and one patient on placebo. Conclusions: Pazopanib maintenance therapy provided a statistically significant and clinically meaningful PFS benefit in patients with AEOC; OS data are not mature. The safety profile of pazopanib in this setting was consistent with its established profile. Clinical trial information: NCT00866697.

Time course of regorafenib-associated adverse events in the phase III CORRECT study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 467-467 ◽  
Author(s):  
Axel Grothey ◽  
Eric Van Cutsem ◽  
Alberto F. Sobrero ◽  
Salvatore Siena ◽  
Alfredo Falcone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Placebo Group ◽  
Adverse Events ◽  
Survival Benefit ◽  
Time Course ◽  
Dose Intensity ◽  
Phase Iii ◽  
Multikinase Inhibitor ◽  
Study Results ◽  
Overall Survival Benefit

467 Background: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs placebo in the randomized phase III CORRECT study. We examined the time course of adverse events (AEs) in the CORRECT study. Methods: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs placebo in the randomized phase III CORRECT study. We examined the time course of adverse events (AEs) in the CORRECT study. Results: The safety population comprised 753 patients (pts): REG n=500; placebo n=253. The mean treatment duration was 12.1 ± 9.7 weeks in the REG group and 7.8 ± 5.2 weeks in the placebo group. Treatment-emergent AEs occurred at any grade in 99.6% of REG pts and 96.8% of placebo pts, at grade 1/2 in 21.6% and 47.8%, respectively, at grade 3 in 56.0% and 26.5%, respectively, and at grade 4/5 in 22.0% and 22.5%, respectively. AEs occurring in ≥10% more REG than placebo pts were fatigue, hand–foot skin reaction (HFSR), anorexia, diarrhea, weight loss, voice changes, hypertension, rash/desquamation, oral mucositis, fever, hyperbilirubinemia, low platelet count. The most frequent AEs deemed to be regorafenib related were HFSR, fatigue, diarrhea, hypertension, and rash/desquamation. The frequency of these AEs over time is shown in the Table. The incidence of HFSR, fatigue, hypertension, and rash/desquamation peaked in cycle 1 and tapered to a relatively stable lower incidence over later cycles. The incidence of diarrhea remained relatively constant throughout treatment. AEs led to dose modification in 66.6% of pts in the REG group and 22.5% in the placebo group. Data on dose intensity across treatment cycles will be presented. Conclusions: In the CORRECT trial, the incidences of the most common AEs in the REG group peaked early during treatment. There appeared to be no evidence for cumulative toxicity of REG. Clinical trial information: NCT01103323. [Table: see text]

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