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Clinical Trial
. 2023 Mar;149(3):1123-1129.
doi: 10.1007/s00432-022-03979-2. Epub 2022 Mar 22.

Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for patients with metastatic colorectal cancer

Yuki Matsubara  1 , Toshiki Masuishi  2 , Takatsugu Ogata  1 , Taiko Nakazawa  1 , Kyoko Kato  1 , Kazuki Nozawa  1 , Yukiya Narita  1 , Kazunori Honda  1 , Hideaki Bando  1 , Hiroya Taniguchi  1 , Shigenori Kadowaki  1 , Masashi Ando  1 , Masahiro Tajika  3 , Kei Muro  1
Affiliations
Clinical Trial

Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for patients with metastatic colorectal cancer

Yuki Matsubara et al. J Cancer Res Clin Oncol. 2023 Mar.

Abstract

Purpose: Fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab is the standard second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to fluoropyrimidines and oxaliplatin. However, the benefits of incorporating fluoropyrimidines into second-line chemotherapy for patients with mCRC who are refractory to fluoropyrimidines are unknown.

Methods: We retrospectively evaluated patients with mCRC who were administered irinotecan plus bevacizumab or FOLFIRI plus bevacizumab as second-line chemotherapy at a single institution from January 2010 to April 2020. We compared the efficacy and safety of irinotecan plus bevacizumab (IRI group) with those of FOLFIRI plus bevacizumab (FOLFIRI group).

Results: Of the 255 enrolled patients, 107 (IRI/FOLFIRI group, 31/76 patients) were eligible for analysis. After a median follow-up of 13.1 months (range 1.2-48.4) and 14.3 months (range 0.9-46.5) for the IRI and FOLFIRI groups, respectively, the median progression-free survival was 6.4 months and 5.8 months [adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI) 0.50-1.34, p = 0.44] and the median overall survival was 16.6 months and 16.5 months (aHR, 1.01; 95% CI 0.59-1.69; p = 0.97) in the IRI and FOLFIRI groups, respectively. All-grade nausea, stomatitis, neutropenia, thrombocytopenia, Grade 3/4 neutropenia, and febrile neutropenia occurred more frequently in the FOLFIRI group than in the IRI group.

Conclusion: Our study suggests omitting fluorouracil from FOLFIRI plus bevacizumab as the second-line chemotherapy decreases adverse events without affecting the treatment efficacy in patients with mCRC who are refractory to fluoropyrimidines. Further randomized prospective studies are warranted to validate our result.

Keywords: Bevacizumab; Chemotherapy; Colorectal cancer; Fluoropyrimidine; Irinotecan.

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Conflict of interest statement

The authors declare the following conflicts of interest: YM received honorania from Takeda, Merck Bio Pharma, and Taiho. TM received honorania from Takeda, Chudai, Merck Bio Pharma, Taiho, Bayer, Eli Lilly, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, and Bristol-myers squibb and research funding from MSD, Daiichi Sankyo, Ono, and Novartis. TO received honorania from Ono, Bristol-myers squibb, Taiho, MSD, and Eli Lilly. TN received honorania from Eli Lilly. YN received honorania from Yakult Honsha, Taiho, Eli Lilly, Daiichi Sankyo, and AstraZeneca and research funding from Ono, and Bristol-myers squibb. YN was also a part of the advisory board of Daiichi Sankyo. HB received honorania from Eli Lilly and Taiho and research funding from Ono. HT received honorania from Taiho, Chugai, Takeda, Eli Lilly, Merck Biopharma, and Yakult Honsha. SK received honorania from Bristol-myers squibb, Chugai, Merck Bio Pharma, Daiichi Sankyo, MSD, Ono, Bayer, Taiho, and Esai and research funding from Ono, Taiho, MSD, Nobelpharma, Bristol-myers squibb, Eli Lilly, and Chugai. MT received honorania from EA Pharma. KM received honorania from Ono, Chugai, Takeda, Taiho, Sanofi, Bristol-myers squibb, Eli Lilly, and Bayer; research funding from Solasia Pharma, Merck Serono, Daiichi Sankyo, Parexel International, Pfizer, MSD, Amgen, ONO, Astellas, Sanofi, Taiho, and Esai; and consulting fees from AstraZeneca, Ono, and Amgen. KM was also a part of the advisory boards of Ono, MSD, AstraZeneca, Daiichi Sankyo, and Solasia Pharma.

Figures

Fig. 1
Fig. 1
Overall survival and progression-free survival. The median follow-up time was 13.1 (range 1.2–48.4) months in the IRI group and 14.3 (range 0.9–46.5) months in the FOLFIRI group. Median progression-free survival (PFS) was 6.4 months in the IRI group and 5.8 months in the FOLFIRI group [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.57–1.38; p = 0.64; adjusted HR 0.82; 95% CI 0.50–1.34, p = 0.44]. PFS was adjusted for previous colorectal resection, the number of metastatic sites, Eastern Cooperative Oncology Group Performance Status (ECOG PS), liver metastasis, and lactate dehydrogenase (LDH) levels. Median overall survival (OS) was 16.6 months in the FOLFIRI group versus 16.5 months in the FOLFIRI group (HR, 0.83; 95% CI 0.51–1.32; p = 0.44; aHR, 1.01; 95% CI 0.59–1.69; p = 0.97). OS was adjusted for previous colorectal resection, the number of metastatic sites, liver metastasis, peritoneal metastasis, and LDH levels
Fig. 2
Fig. 2
Best response. Among 107 patients, 27 patients in the IRI group and 53 patients in the FOLFIRI group had measurable lesions. The deepness of response (DpR) presented as a waterfall plot was defined as the rate of tumor shrinkage from baseline CT. In the IRI group, the response rate (RR) and disease control rate (DCR) were 26% and 74%, respectively. In the FOLFIRI group, RR and DCR were 12% and 72%, respectively. CR complete response, PR partial response, SD stable disease, PD progressive disease, NE not evaluated
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