Randomized, phase II study of bevacizumab with mFOLFOX6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: Resectability and safety in OLIVIA.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3619-3619 ◽  
Author(s):  
Thomas Gruenberger ◽  
John A. Bridgewater ◽  
Ian Chau ◽  
Pilar Garcia Alfonso ◽  
Michel Rivoire ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Progression Free Survival ◽  
Remnant Liver ◽  
Resection Rate ◽  
Open Label ◽  
R1 Resection ◽  
Unresectable Liver Metastases ◽  
Grade 3 ◽  
Hepatic Lesions ◽  
Ecog Ps

3619^ Background: Patients (pts) with unresectable colorectal cancer liver-only metastases (CLMs) may become resectable after downsizing by chemotherapy (CT) and biologic therapy. Although biologics are thought to improve overall response rate (ORR), the optimal combination of a biologic and CT for resectability remains uncertain. Methods: This open-label, multinational study randomized pts with unresectable CLMs to bevacizumab (BEV) plus mFOLFOX6 or FOLFOXIRI q2w. Resectability was assessed by interdisciplinary review. Unresectability was defined as ≥1 of the following: no possibility of upfront R0/R1 resection of all hepatic lesions, <30% estimated residual liver after resection, or disease in contact with major vessels of the remnant liver. The primary end point was overall resection rate (R0/R1/R2). Results: From 10/2008 to 12/2011, 80 pts were randomized to mFOLFOX6-BEV (n=39) or FOLFOXIRI-BEV (n=41). Pt characteristics were male (46% vs 71%), aged ≥60 y (36% vs 63%), ECOG PS of 1 (23% vs 37%), and ≥5 target CLMs (49% vs 49%) in the mFOLFOX6-BEV and FOLFOXIRI-BEV arms, respectively. Resection rate, ORR, and progression-free survival (PFS) data are shown (Table). Grade ≥3 adverse events (AEs) occurred in 84% and 95% of pts receiving mFOLFOX6-BEV and FOLFOXIRI-BEV, respectively, and included neutropenia (35% vs 48%; febrile, 8% vs 13%) and diarrhea (14% vs 28%). Conclusions: The results suggest that FOLFOXIRI-BEV improves resection rates, ORR, and long-term outcomes vs mFOLFOX6-BEV in pts with initially unresectable CLMs. CT- and BEV-related AEs occurred with the expected incidence and were manageable. FOLFOXIRI-BEV should be evaluated further as an effective regimen to downsize CLMs. Clinical trial information: NCT00778102. [Table: see text]

A randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/l-LV/oxaliplatin (mFOLFOX6) plus bevacizmab in patients with metastatic colorectal cancer: The SOFT study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3519-3519 ◽  
Author(s):  
Daisuke Takahari ◽  
Yasuhide Yamada ◽  
Hiroshi Matsumoto ◽  
Hideo Baba ◽  
Kazuhiro Yoshida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Open Label ◽  
Phase Iii Trial ◽  
Open Label Phase ◽  
Grade 3 ◽  
Ecog Ps

3519 Background: Several studies of oxaliplatin plus S-1 combination therapy (SOX) conducted in Asia have shown promising efficacy and safety for metastatic colorectal cancer (mCRC), suggesting the potential to replace mFOLFOX6. We performed a randomized phase III trial to determine whether SOX plus bevacizmab (SOX+Bev) is non-inferior to mFOLFOX6 plus bevacizmab (mFOLFOX6+Bev) in terms of progression-free survival (PFS). Methods: The SOFT study was a randomized, open-label, phase III trial. Chemotherapy-naïve patients (pts) with mCRC, an ECOG PS of 0-1, and adequate organ functions were randomized to receive either mFOLFOX6+Bev (5 mg/kg of bevacizumab, followed by 200 mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed by a 400 mg/m2 bolus of 5-FU on day 1 and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or SOX+Bev (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1, and 40−60 mg of S-1 twice daily for 2 weeks, followed by a 1-week rest). The primary endpoint was PFS. A sample size of 225 pts per group was estimated to be necessary based on a median PFS of 10.0 months in each group and an 80% power to demonstrate non-inferiority of SOX+Bev with a 2.5-month margin (hazard ratio, HR = 1.33) and a 2-sided alpha of 0.05. Results: A total of 512 pts were enrolled from February 2009 to March 2011. Data were analyzed after confirming >388 events as planned. Demographic factors were well balanced. Pts received a median of 12 cycles (1 cycle = 2 weeks) of mFOLFOX6+Bev and 8 cycles (1 cycle = 3 weeks) of SOX+Bev (range: 1−16). Median PFS was 11.5 months (95% CI: 10.7−13.2) with mFOLFOX6+Bev and 11.7 months (95% CI: 10.7−12.9) with SOX+Bev. The adjusted HR for PFS was 1.043 (95% CI: 0.860−1.266), and the p value for non-inferiority was 0.0139. Response rate was 62.7% with mFOLFOX6+Bev and 61.5% with SOX+Bev. Grade 3/4 toxicities (%) with mFOLFOX6+Bev/SOX+Bev were leukopenia 8.4/2.4, neutropenia 33.7/8.8, anorexia 1.2/5.2, and diarrhea 2.8/9.2. Conclusions: SOX+Bev is non-inferior to mFOLFOX6+Bev with respect to PFS as 1st-line treatment for mCRC and thus can replace mFOLFOX6+Bev. Clinical trial information: JapicCTI-090699.

Phase I dose escalation and pharmacokinetics study of intravenous aflibercept plus irinotecan, 5-fluorouracil, and folinic acid (FOLFIRI) in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 538-538 ◽  
Author(s):  
K. Yamazaki ◽  
T. Yoshino ◽  
K. Yamaguchi ◽  
N. Boku ◽  
N. Machida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Escalation ◽  
Safety Issue ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Open Label ◽  
Dose Escalation Study ◽  
Grade 3 ◽  
Ecog Ps

538 Background: Aflibercept (AF), a recombinant fusion protein, is a potent inhibitor of vascular endothelial growth factor. This study assessed the safety, dose limiting toxicities (DLTs), recommended dose (RD), and the pharmacokinetics (PK) of AF in combination with FOLFIRI. Methods: This was an open-label, sequential-cohort, dose-escalation study of intravenous AF administered every 2 weeks, in combination with FOLFIRI (fixed doses) in patients (pts) with metastatic colorectal cancer (MCRC). Two dose levels (DL) of AF (2 and 4 mg/kg) were set, and 3-6 pts were to be recruited in each DL. DLTs were to be evaluated in the first 2 cycles. RD was defined as the highest AF dose at which <33% of all evaluable pts experienced DLTs. After establishment of RD, 10 additional pts were treated at RD. PK of AF, irinotecan, SN38, and 5-FU were studied in cycle 1. Results: 16 pts (3 at 2 mg/kg and 13 at 4 mg/kg) with MCRC were treated (M/F, 10/6; median age, 57.0 [47-69]; and ECOG PS 0/1, 9/7), and all had received prior chemotherapies. A total of 131 cycles of AF + FOLFIRI were administered at the two DLs of AF (2 and 4 mg/kg). No DLT was observed. The most common all-causality grade 3/4 adverse events were neutropenia (75.0 %) including one febrile neutropenia after DLT evaluation period and hypertension (25.0%). There was no major safety issue at the RD. Response rate and progression free survival at RD (N=13 pts) was 7.8% and 7.6 month, respectively. Conclusions: RD was determined as 4 mg/kg in this first clinical study of AF in Japanese pts with MCRC. The combination of AF (4 mg/kg) and FOLFIRI was well tolerated in line with results of prior overseas studies. The PK results in Japanese patients showed similar tendency to those reported in patients from other regions of the world. [Table: see text]

Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3532-3532
Author(s):  
Bert H. O'Neil ◽  
Calin Cainap ◽  
Eric Van Cutsem ◽  
Vera A. Gorbunova ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
High Dose ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Bevacizumab Treatment ◽  
Grade 3 ◽  
Weight Decrease ◽  
Ecog Ps

3532 Background: Linifanib is a potent and selective inhibitor of VEGF/PDGF receptors. This trial assessed the efficacy and safety of mFOLFOX6 in combination with linifanib or bevacizumab as second-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients (pts) with measurable mCRC refractory to 1 prior regimen and ECOG PS 0–1, stratified by prior bevacizumab treatment and radiotherapy, were randomized to receive mFOLFOX6 with bevacizumab 10 mg/kg on day (d) 1 of 14-d cycle (Arm A), mFOLFOX6 with daily linifanib 7.5 mg (Arm B), or mFOLFOX6 with daily linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS). Severity of adverse events (AEs) was graded using NCI-CTCAE v3.0. Results: 148 pts were randomized at 45 sites in 14 countries. 32 pts (21.6%) had received prior bevacizumab. PFS and response data are shown below (Table). Median survival (OS) was not reached at median follow up 7.6 months. Palmar-plantar erythrodysesthesia (PPE) was the only Grade 3/4 AE significantly higher on linifanib (high dose, 16.3%) vs. bevacizumab (0%). Rate of any Grade 3+ AE was significantly higher on linifanib vs. bevacizumab.Hypertension rates were 41.7% (Arm A), 40.0% (Arm B), and 36.7% (Arm C). AEs dose-related to linifanib were constipation, proctalgia, stomatitis, fatigue, weight decrease, decreased appetite, and PPE. Conclusions: The addition of linifanib to mFOLFOX6, compared to mFOLFOX6 + bevacizumab, did not provide a PFS advantage for mCRC. OS results will be updated for conference presentation. [Table: see text]

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4692-TPS4692 ◽  
Author(s):  
Mario A. Eisenberger ◽  
Anne-Claire Hardy-Bessard ◽  
Loic Mourey ◽  
Paul N. Mainwaring ◽  
Daniel Ford ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Measurable Disease ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.

scholarly journals Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000698
Author(s):  
Jean-Baptiste Bachet ◽  
Lucjan Wyrwicz ◽  
Timothy Price ◽  
Chiara Cremolini ◽  
Jean-Marc Phelip ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Open Label ◽  
Patient Reported ◽  
Registration Number ◽  
Grade 3

BackgroundIn RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.MethodsIn this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).Results793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03–14.72). There was no clinically relevant change from baseline in QoL.ConclusionsPRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.Trial registration numberNCT03306394.

A randomized phase II study of mFOLFOX6 plus bevacizumab versus mFOLFOX6 plus cetuximab for previously untreated, liver-limited metastatic colorectal cancer that is unsuitable for resection (ATOM trial).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 734-734 ◽  
Author(s):  
Hiroyuki Uetake ◽  
Yasunori Emi ◽  
Takeharu Yamanaka ◽  
Kei Muro ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Resection Rate ◽  
Exon 2 ◽  
Two Agents ◽  
Line Setting ◽  
Ecog Ps

734 Background: It is still a topic of ongoing debate as to which of the two agents, anti-VEGF antibody or anti-EGFR antibody, is more effective in patients with KRAS Exon 2 or RAS wild-type metastatic colorectal cancer (mCRC) in the first-line setting. ATOM is a multicenter, randomized trial comparing mFOLFOX6 plus bevacizumab (Bmab arm) with mFOLFOX6 plus cetuximab (Cmab arm) in patients with liver-limited metastases unsuitable for upfront resection. Methods: Patients with previously untreated mCRC were eligible if they had ≥5 liver-limited metastatic lesions and/or had liver-limited metastases with the maximum lesion diameter of > 5cm. Patients with KRAS Exon2-wild were registered but after Jan 2015 limited to those with all RAS-wild. Primary endpoint was progression-free survival (PFS), which was defined as the time from randomization to disease progression, recurrence after resection by surgery, or death from any cause (Central review). Key secondary endpoints included overall response rate (ORR), liver resection rate, and overall survival (OS). Results: A total of 122 pts were enrolled between May 2013 and April 2016. Of 116 eligible (59 in the Cmab arm and 57 in the Bmab arm), median age was 65/64 in the Cmab/Bmab arm; ECOG PS 0, 86/89%; all RAS wt, 98/95%; left-sided primary tumor, 76/84%. Efficacy results were summarized in the table. With a median follow-up of 24.3 months, the median PFS was 15.0 months in Cmab arm and 11.6 months in the Bmab arm with a hazard ratio of 0.803 (95%CI, 0.513–1.256), whereas ORR was 86% in the Cmab arm and 68% in the Bmab arm. Liver resection rate was 49% and 56% in the Cmab arm and the Bmab arm, respectively. Conclusions: In patients considered unsuitable for upfront resection of liver-limited metastasis, the two agents showed a similar efficacy. OS result will be presented elsewhere. Clinical trial information: NCT01836653. [Table: see text]

Neoadjuvant FOLFIRINOX and IMRT concurrent with FDR-gemcitabine in patients with borderline resectable pancreatic cancer (BRPC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 381-381
Author(s):  
Nguyen H. Tran ◽  
Vaibhav Sahai ◽  
Kent A. Griffith ◽  
Hari Nathan ◽  
Ravi Kaza ◽  
...  
Keyword(s):  
Early Death ◽  
Progression Free Survival ◽  
Primary Objective ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Entire Cohort ◽  
Grade 3 ◽  
Ecog Ps

381 Background: Preoperative therapy in BRPC is intended to increase the likelihood of R0 resection although an optimal regimen is yet to be defined. Methods: Patients (pts) with BRPC (NCCNv.2.2010 guidelines) and ECOG PS 0-1 were enrolled in a single-institution, phase II trial (NCT01661088). Pts received FOLFIRINOX x 6, followed by IMRT (50 Gy in 25 fractions) concurrent with FDR-gemcitabine 1 g/m2 on days 1, 8, 22, 29. Two additional FDR-gemcitabine infusions completed pre-operative treatment. Pancreatic protocol CT scans (dual phase, 0.65 mm slices) were performed after 4 infusions of FOLFIRINOX, 3 weeks after IMRT, and at treatment completion. Pts without distant disease were offered surgical exploration. The primary objective was to determine R0 resection rate. Secondary objectives included progression free survival (PFS), overall survival (OS), response rate and safety. Results: A total of 25 pts (64% men) median age 60 years (range 47-77) were enrolled from 11/2011 through 01/2017. Twenty-one (84%) pts completed FOLFIRINOX and 19 (76%) all protocol therapy. Treatment-related grade 3-4 adverse events ( > 10%) included neutropenia (40%), nausea/vomiting (28%), diarrhea (16%) and fatigue (12%). One early death and 1 discontinuation due to toxicity occurred during FOLFIRINOX. Response to pre-op therapy included 11 PR, 9 SD, 3 PD and 2 NE. Of 25 treated pts, 18 (72%) had laparotomy and 13 (52%) underwent resection (all R0). The median PFS and OS were 18.1 (95% CI, 10.6 to 25.1) and 24.2 (95% CI, 12.6 to 40.0) months, respectively. The median OS for R0 resected pts was 37.1 (95% CI, 15.4 – not reached) months. Conclusions: Neoadjuvant therapy with FOLFIRINOX, followed by IMRT with concurrent FDR-gemcitabine in BRPC is feasible and tolerated. While R0 resection rate was not obviously improved, OS of the entire cohort and especially in R0 resected pts was favorable. Clinical trial information: NCT01661088.

Regorafenib for previously treated metastatic colorectal cancer (mCRC): A subgroup analysis of 364 patients in the USA treated in the international, open-label phase IIIb CONSIGN study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 735-735 ◽  
Author(s):  
Udit Verma ◽  
Yull Edwin Arriaga ◽  
Heinz-Josef Lenz ◽  
Charles A. Henderson ◽  
Jyotsna Fuloria ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Open Label ◽  
Phase Iiib ◽  
The Usa ◽  
Grade 3 ◽  
Ecog Ps

735 Background: In the phase III CORRECT study, regorafenib significantly improved overall survival and progression-free survival (PFS) vs placebo in patients with treatment-refractory mCRC. CONSIGN (NCT01538680) was a large phase IIIb study that included 2872 patients from 25 countries; it was designed to provide continued access to regorafenib for patients with mCRC who failed standard therapy and to further characterize the safety of regorafenib. In CONSIGN, adverse events (AEs) and PFS were consistent with those reported in phase III studies. We present a retrospective subgroup analysis of patients enrolled in CONSIGN in the USA. Methods: Patients with mCRC who progressed on standard therapies and had an ECOG PS 0─1 received regorafenib 160 mg QD for the first 3 weeks of each 4-week cycle. Treatment was continued until disease progression, death, or unacceptable toxicity. The primary endpoint was safety. PFS (per investigator) was the only efficacy variable assessed. Results: A total of 364 patients in the USA were assigned to treatment (all evaluable for safety). The median age was 60 years; 38% and 62% had ECOG PS 0 and 1, respectively. KRAS mutation was present in 59%, KRAS wt in 38%; 74% had ≥ 3 prior regimens for metastatic disease. Median duration of treatment was 2.3 months (range: 0–30). Median PFS (95% CI) was 2.3 (2.0–2.6) months (2.1 months KRAS wt; 2.3 months KRAS mutant). NCI-CTCAE v4.0 grade ≥ 3 AEs occurred in 81% of patients and were considered drug-related in 53% (Table). Grade ≥ 3 hepatobiliary disorders occurred in 2%. Grade ≥ 3 treatment-emergent laboratory toxicities included bilirubin (9%), AST (6%), and ALT (3%). Conclusions: In patients from the USA enrolled in CONSIGN, the safety profile of regorafenib was consistent with that of the overall population and the known safety profile of regorafenib in mCRC. Median PFS was in the range of that reported in phase III trials. Clinical trial information: NCT01538680. [Table: see text]

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