Erschienen in:
01.06.2023 | Original Article
Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study
verfasst von:
Satoshi Dote, Eiji Shiwaku, Emiko Kohno, Ryohei Fujii, Keiji Mashimo, Naomi Morimoto, Masaki Yoshino, Naoki Odaira, Hiroaki Ikesue, Masaki Hirabatake, Katsuyuki Takahashi, Masaya Takahashi, Mari Takagi, Satoshi Nishiuma, Kaori Ito, Akane Shimato, Shoji Itakura, Yoshitaka Takahashi, Yutaka Negoro, Mina Shigemori, Hiroyuki Watanabe, Dai Hayasaka, Masahiko Nakao, Misaki Tasaka, Emi Goto, Noriaki Kataoka, Ayako Yokomizo, Ayako Kobayashi, Yoko Nakata, Mafumi Miyake, Yaeko Hayashi, Yoshie Yamamoto, Taiki Hirata, Kanako Azuma, Katsuya Makihara, Rino Fukui, Akira Tokutome, Keiji Yagisawa, Shinji Honda, Yuji Meguro, Shota Suzuki, Daisuke Yamaguchi, Hitomi Miyata, Yuka Kobayashi, The IMBERA Investigators
Erschienen in:
International Journal of Clinical Oncology
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Ausgabe 8/2023
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Abstract
Background
The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC).
Methods
mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2–3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups.
Results
We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28–55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23–5.51), 1.51 (1.01–2.27), and 1.04 (0.76–1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01).
Conclusion
Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.