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Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Bevacizumab | Research article

Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer

Authors: Shun Yamamoto, Kengo Nagashima, Takeshi Kawakami, Seiichiro Mitani, Masato Komoda, Yasushi Tsuji, Naoki Izawa, Kentaro Kawakami, Yoshiyuki Yamamoto, Akitaka Makiyama, Kentaro Yamazaki, Toshiki Masuishi, Taito Esaki, Takako Eguchi Nakajima, Hiroyuki Okuda, Toshikazu Moriwaki, Narikazu Boku

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab.

Methods

The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis.

Results

Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0–1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46–1.34], p = 0.373, adjusted HR: 0.87 [0.41–1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38–1.12], p = 0.125, adjusted HR 0.53 [0.27–1.07], p = 0.078).

Conclusion

In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.
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Literature
3.
go back to reference Yoshino T, Arnold D, Taniguchi H, Pentheroudakis G, Yamazaki K, Xu RH, et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann Oncol. 2018;29(1):44–70. https://doi.org/10.1093/annonc/mdx738.CrossRefPubMed Yoshino T, Arnold D, Taniguchi H, Pentheroudakis G, Yamazaki K, Xu RH, et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann Oncol. 2018;29(1):44–70. https://​doi.​org/​10.​1093/​annonc/​mdx738.CrossRefPubMed
5.
go back to reference Grothey A, Flick ED, Cohn AL, Bekaii-Saab TS, Bendell JC, Kozloff M, et al. Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study. Pharmarcoepidemiol Drug Saf. 2014;23(7):726–34. https://doi.org/10.1002/pds.3633.CrossRef Grothey A, Flick ED, Cohn AL, Bekaii-Saab TS, Bendell JC, Kozloff M, et al. Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study. Pharmarcoepidemiol Drug Saf. 2014;23(7):726–34. https://​doi.​org/​10.​1002/​pds.​3633.CrossRef
12.
go back to reference Venook AP, Niedzwiecki D, Innocenti F, et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 016;34(Suppl):3504. Venook AP, Niedzwiecki D, Innocenti F, et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 016;34(Suppl):3504.
13.
go back to reference Venook AP, Ou FS, Lenz HJ, et al. Primary tumor location as an independent prognostic marker from molecular features for overall survival in patients with metastatic colorectal cancer: analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2017;35(Suppl):3503. Venook AP, Ou FS, Lenz HJ, et al. Primary tumor location as an independent prognostic marker from molecular features for overall survival in patients with metastatic colorectal cancer: analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2017;35(Suppl):3503.
16.
go back to reference Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(31):4706–13. https://doi.org/10.1200/JCO.2009.27.6055.CrossRefPubMed Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(31):4706–13. https://​doi.​org/​10.​1200/​JCO.​2009.​27.​6055.CrossRefPubMed
18.
19.
go back to reference Yamada Y, Denda T, Gamoh M, Iwanaga I, Yuki S, Shimodaira H, et al. S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase III, noninferiority trial. Ann Oncol. 2018;29(3):624–31. https://doi.org/10.1093/annonc/mdx816.CrossRefPubMed Yamada Y, Denda T, Gamoh M, Iwanaga I, Yuki S, Shimodaira H, et al. S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase III, noninferiority trial. Ann Oncol. 2018;29(3):624–31. https://​doi.​org/​10.​1093/​annonc/​mdx816.CrossRefPubMed
20.
go back to reference Nixon A, Sibley A, Hatch AJ, et al. Blood-based biomarkers in patients (pts) with metastatic colorectal cancer (mCRC) treated with FOLFOX or FOLFIRI plus bevacizumab (Bev), cetuximab (Cetux), or bev plus Cetux: Results from CALGB 80405 (Alliance). J Clin Oncol. 2016;34(Suppl):3597. Nixon A, Sibley A, Hatch AJ, et al. Blood-based biomarkers in patients (pts) with metastatic colorectal cancer (mCRC) treated with FOLFOX or FOLFIRI plus bevacizumab (Bev), cetuximab (Cetux), or bev plus Cetux: Results from CALGB 80405 (Alliance). J Clin Oncol. 2016;34(Suppl):3597.
21.
go back to reference Van Cutsem E, Paccard C, Chiron M, et al. Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial. Clin Cancer Res. 2020;26(3):717–25. Van Cutsem E, Paccard C, Chiron M, et al. Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial. Clin Cancer Res. 2020;26(3):717–25.
26.
28.
go back to reference Van Custem E, Joulain F, Hoff PM, et al. Aflibercept plus FOLFIRI vs. placebo plus FOLFIRI in second-line metastatic colorectal Cancer: a post hoc analysis of survival from the phase III VELOUR study subsequent to exclusion of patients who had recurrence during or within 6 months of completing adjuvant Oxaliplatin-based therapy. Target Oncol. 2016;11(3):383–400. https://doi.org/10.1007/s11523-015-0402-9.CrossRef Van Custem E, Joulain F, Hoff PM, et al. Aflibercept plus FOLFIRI vs. placebo plus FOLFIRI in second-line metastatic colorectal Cancer: a post hoc analysis of survival from the phase III VELOUR study subsequent to exclusion of patients who had recurrence during or within 6 months of completing adjuvant Oxaliplatin-based therapy. Target Oncol. 2016;11(3):383–400. https://​doi.​org/​10.​1007/​s11523-015-0402-9.CrossRef
30.
32.
go back to reference Van Custem E, Kohne CH, Lang I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2012;29:2011–9. Van Custem E, Kohne CH, Lang I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2012;29:2011–9.
Metadata
Title
Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer
Authors
Shun Yamamoto
Kengo Nagashima
Takeshi Kawakami
Seiichiro Mitani
Masato Komoda
Yasushi Tsuji
Naoki Izawa
Kentaro Kawakami
Yoshiyuki Yamamoto
Akitaka Makiyama
Kentaro Yamazaki
Toshiki Masuishi
Taito Esaki
Takako Eguchi Nakajima
Hiroyuki Okuda
Toshikazu Moriwaki
Narikazu Boku
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08890-6

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