Phase II trial of irinotecan plus s-1 (IRIS) with cetuximab (IRIS/Cet) as second-line treatment in patients with KRAS wild-type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 746-746 ◽  
Author(s):  
Yoshito Komatsu ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Ayumu Hosokawa ◽  
Michio Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Safety Analysis ◽  
Rank Test ◽  
Treatment Schedule ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Administration Interval

746 Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of IRIS/Cet as second-line treatment in patients with KRAS wild type mCRC. RR was 33.3% (95% CI, 20.8%-45.9%), therefore primary endpoint was met (Muto et al. ESMO 2014 ). Here we report an exploratory analysis of outcomes based on administration interval of Cet (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS WT. Pts. received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100 mg/m2 on days 1 and 15 repeated every 28 days. Cet was administrated 400 mg/m2 as loading dose and continued 250 mg/m2 every week or 500 mg/m2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS, OS, and TTF. Results: Between March 2010 and September 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician choice, 34 pts. of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW group and 31.8% in the BW group (p=1.000). Median PFS was 4.2 months (95% CI 3.5−4.9) in the EW group and 6.1 months (4.1-8.1) in the BW group (HR 0.752, 95% CI 0.413−1.372, p=0.350). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW group vs. 52.2% in the BW group: p=0.005) and stomatitis (2.9% in the EW group vs. 30.4% in the BW group: p=0.046), these were significantly more common in the BW group. Conclusions: IRIS/Cet appeared to be highly effective with RR and PFS in the both treatment schedule, and also had met the primary endpoint. Diarrhea and stomatitis were significantly more common in the BW group. Therefore, in case of treatment with IRIS, cetuximab should be administered weekly. Clinical trial information: 000004882.

Updated analysis of phase II trial of irinotecan/s-1/cetuximab (IRIS/Cet) as second-line treatment in patients with KRAS exon2 wild type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 771-771
Author(s):  
Tomohiro Kondo ◽  
Satoshi Yuki ◽  
Yasuyuki Kawamoto ◽  
Yasushi Tsuji ◽  
Ayumu Hosokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Patient Characteristics ◽  
Safety Analysis ◽  
Rank Test ◽  
Treatment Schedule ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Administration Interval

771 Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of irinotecan, S-1 (IRIS) plus cetuximab as second line treatment in patients with KRAS exon2 wild type mCRC. Response rate (RR) was 33.3% (95%CI 20.8-45.9%), therefore primary endpoint was met (Muto O, et al. ESMO 2014). Here we report an exploratory analysis of outcomes based on administration interval of cetuximab (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed mCRC, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS exon2 wild type. Patients received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on day 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m2 as loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS and OS. Results: Between Mar 2010 and Sep 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician’s choice, 34 patients of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW and 31.8% in the BW (p = 1.000). Median PFS was 4.2 months in the EW and 6.1 months in the BW (HR 0.752, p = 0.350). Median OS was 8.9 months in the EW and 10.7 months in the BW (HR 0.902, p = 0.737). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW vs 52.2% in the BW: p = 0.005) and stomatitis (2.9% in the EW vs 30.4% in the BW group: p = 0.046), these were significantly more common in the BW. Conclusions: IRIS/Cet appeared to be highly effective with RR, PFS and OS in the both treatment schedule. Diarrhea and stomatitis were significantly more common in the BW. Therefore, in case of treatment with IRIS/Cet should be administered in the EW. Clinical trial information: UMIN000004882.

Safety analysis of the randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 86-86
Author(s):  
Takanori Watanabe ◽  
Akihito Tsuji ◽  
Manabu Shiozawa ◽  
Hirofumi Ota ◽  
Hironaga Satake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Safety Analysis ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Randomized Phase Ii ◽  
First Line Treatment ◽  
Triplet Regimen

86 Background: Triplet regimens, FOLFOXIRI, combined with bevacizumab (bev) or panitumumab have been shown to be superior in terms of early tumor shrinkage (ETS) and depth of response (DpR) compared to doublet regimen plus bev or triplet regimen in patients with RAS wild-type metastatic colorectal cancer (mCRC), in the TRIBE trial ( N Engl J Med 2014) or VOLFI trial ( J Clin Oncol 2019), respectively. There have been few studies which directly compared cetuximab (cet) with bev when combined with triplet regimen. Therefore, we investigated the efficacy and safety of bev vs. cet in combination with FOLFOXIRI in previously untreated mCRC patients with RAS wild-type tumors. Methods: This trial was a randomized phase II trial to evaluate modified (m)-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, 5-FU 2400 mg/m2) plus cet vs. bev as first-line treatment in terms of the DpR during the entire course as the primary endpoint in 360 patients with RAS wild-type mCRC (ClinicalTrials.gov Identifier: NCT02515734). The experimental arm with cet was considered to be active if the difference of median DpR was over 12.5% compared with the bev arm, under the conditions of significance level of 0.05 and power of 0.85. Secondary endpoints included the ETS at week 8, progression-free survival, overall survival, secondary resection rate, and toxicity. Results: A total of 359 patients were enrolled between July 2015 and June 2019. For the safety analysis set (median age 65y, 64% male, PS0/1:91%/9%, left/right primary:83%/17%), 173 and 175 patients were randomly assigned to the cet and bev arms, respectively, some patients were excluded for the safety analysis due to the violation of inclusion criteria (6 for cet arm and 5 for bev). On the cutoff date of September 2020, median number of cycles administered was 10 (range, 1-51) for the cet arm and 12 (range, 1-51) for the bev arm. The incidence of severe adverse events (AEs) was 25.4% (44/173) for the cet arm and 25.7% (45/175) for the bev arm, respectively. The following AEs of grade 3-4 were observed more frequently in the cet arm compared to the bev arm: oral mucositis (9.2% vs. 2.3%), diarrhea (12.1% vs. 8.0%), dermatitis acneiform (12.1% vs. 0%), and hypomagnesemia (4.0% vs. 0%). The treatment-related death occurred in 2 patients of the cet arm, while no patients in the bev arm. The rate of treatment discontinuation due to AEs of any cause was comparable between the cet and bev arms (7% vs. 9%). Conclusions: This safety analysis indicated that both regimens of m-FOLFOXIRI plus cet or bev were tolerable in RAS wt mCRC patients although some frequent severe AEs were observed. Clinical trial information: UMIN000018217.

Phase II trial of irinotecan, S-1, and bevacizumab (IRIS/Bev) combination chemotherapy as second line for advanced colorectal cancer (NCCSG04).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 496-496
Author(s):  
Yasumasa Takii ◽  
Kouichi Hurukawa ◽  
Satoshi Maruyama ◽  
Toshiyuki Yamazaki ◽  
Jun Nishimura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Line Therapy

496 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853-860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for metastatic colorectal cancer (mCRC), with progression-free survival as the primary endpoint. IRIS plus bevacizumab (IRIS/Bev) was reported an active and generally well-tolerated first-line treatment for mCRC (Yuki et al. ASCO 2012 #3593). We planned a Phase II trial to evaluate the efficacy and safety of IRIS/Bev as second-line therapy for patients with mCRC. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2 and Bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety. Results: From 08/12 until 11/06, 35 patients were enrolled. One patient did not start therapy. Thirty-four patients were investigated. Median age was 63 years (range, 38 to 82). Twenty-five patients were male. The mean of relative dose intensity of TS-1/Irinotecan/Bev were respectively 92.1%/87.0%/86.2%. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 9.3 months, median TTF was 8.2 month and median survival time 23.1 month. On safety analysis, the incidence of grade 3 or 4 adverse reactions were as follows: neutropenia, 14.7%; fatigue, 14.7%; white blood cell decreased, 11.8%; anorexia, 8.8%; anemia, 8.8%; diarrhea, 2.9%; proteinuria, 5.9%; thromboembolic event, 2.9%. Conclusions: IRIS/Bev is an active and well-tollarated second-line treatment for patients with mCRC. Clinical trial information: UMIN000001631.

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