Bevacizumab plus mFOLFOX6/FOLFIRI sequential bevacizumab plus capecitabine maintenance in RAS-mutated advanced colorectal cancer: A real-world study of first-line/second-line conversion therapy.
Authors: Yan Ying , He Yifu , Wang Gang , Cao Lulu , Luo Huiqin , Hu Xiaoxiu , Chen Wenju , Wu Shusheng , Li Huimin , Ke Lihong , Xu Huijun , Niu Jiayu , Wang Chunxu 
Published: January 2025

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B
ackground:
Currently, the standard first-line/second-line treatment for advanced colorectal cancer with RAS mutations is chemotherapy combined with bevacizumab. Patients with colorectal cancer confirmed maintenance therapy can effectively improve progression-free survival, improve patient quality of life. Therefore, this study aims to evaluate the efficacy and safety of bevacizumab combined with mFOLFOX6/FOLFIRI sequential bevacizumab combined with capecitabine as first-line/second-line conversion therapy for RAS-mutated advanced colorectal cancer.
M
ethods:
This is an open-label, single-center study in previously untreated patients with RAS mutant mCRC. Eligible patients received first-line chemotherapy of bevacizumab (5mg/m
2
) combined with mFOLFOX6/FOLFIRI for 12 cycles randomly, during which the efficacy was assessed every 4 cycles, then followed by bevacizumab(7.5mg/m
2
) in combination with capecitabine maintenance therapy which assessed every 2 cycles until disease progression, and then switched to the second-line therapy FOLFIRI/mFOLFOX6 combined with bevacizumab which was assessed every 4 cycles until disease progression or intolerable toxicity. Imaging studies were performed to assess treatment efficacy according to RECIST1.1 criteria, and the primary endpoint was progression-free survival (PFS), including first-line PFS and second-line PFS after progression, and the secondary endpoints included disease response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
R
esults:
This study recruited 78 subjects from January 2021 to May 2024. As of September 10, 2024, a total of 70 subjects were analyzable for the first-line treatment, of which 6 subjects met the surgical criteria after treatment and achieved NED status; 45 patients reached the first-line PFS endpoint, with a median PFS (mPFS) of 249 days (95% CI: 204.4-293.6), an ORR of 38.6%, and a DCR of 95.7% . Twenty patients entered the first-line maintenance therapy, with a mPFS of 358 days (95% CI: 53.8-662.2). For the second-line treatment, a total of 43 subjects were analyzable, of which 35 patients reached the second-line PFS endpoint, with a second-line mPFS of 171 days (95% CI: 89.8-252.1). 41 subjects underwent at least one efficacy evaluation, with ORR of 14.6% and DCR of 75.6%. The most common grade 3 treatment-related adverse events were neutropenia, leukopenia, anemia, hypertension, diarrhea, and thrombocytopenia. There were no treatment-related deaths. No new adverse events occurred during the entire combination treatment period.
C
onclusions:
This real world study has demonstrated good tolerability and encouraging clinical efficacy, especially with potential implications for treatment planning and management strategies for advanced colorectal cancer with RAS mutations.
Clinical trial information: ChiCTR2100042553
.