Real-World Data Analysis of Second-Line Antiangiogenic Targeted Treatments Following Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies and First-Line FOLFOX for Patients with Metastatic Colorectal Cancer

Abstract

Introduction Evidence is lacking on second-line and later treatments for patients with RAS wild-type colorectal cancer (CRC) who receive first-line anti-epidermal growth factor receptor (EGFR) antibody therapy. In this study, we explored the real-world treatment sequences, treatment duration, and factors associated with treatment sequences and durations in Japanese patients with CRC. Methods This retrospective observational cohort study used a Japanese administrative claims database (April 2008 to July 2021). Patients with confirmed CRC (presumed RAS wild-type) who received first-line FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) plus anti-EGFR therapy in or after May 2016, followed by second-line irinotecan-based chemotherapy plus an antiangiogenic drug, were included. Treatment durations were estimated by the Kaplan–Meier method. Cox regression analysis was used to identify factors associated with treatment duration. Results Analysis populations consisted of 1163 (first-line and second-line) and 645 (third-line) patients. At the start of first-line therapy, 67.8% of patients were male, the mean age was 64 years, 83.4% had left-sided CRC, and 84.3% were prescribed FOLFOX plus panitumumab. For second-line therapy, patients were prescribed bevacizumab (63%), ramucirumab (27%), or aflibercept beta (10%). Median (95% CI) treatment durations from the start of second-line therapy to the end of antitumor drug therapies were similar for bevacizumab (12.5 months [11.2, 14.0]), ramucirumab (12.5 months [11.2, 14.8]), and aflibercept beta (14.0 months [10.4, 17.0]). Treatment duration from second-line was positively associated with first-line treatment duration of 6 months or more, CRC surgery before starting first-line therapy, and liver surgery during first-line therapy, and was negatively associated with use of nonsteroidal anti-inflammatory drugs before second-line therapy. Conclusion Real-world data revealed that all three antiangiogenic drugs were used as second-line therapy after first-line anti-EGFR antibodies and showed similar treatment durations. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02122-4.

Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study

“…[ 18 ]. Two recent administrative claims database studies [ 24 , 25 ] addressed this issue: among mCRC patients who failed first-line chemotherapy with fluoropyrimidines and oxaliplatin plus BEV [ 24 ], the time to treatment failure, defined as the time from initial second-line chemotherapy to treatment termination due to any cause or death, was significantly longer in the FOLFIRI plus BEV group compared with that in the FOLFIRI plus RAM (hazard ratio, 1.40; 95% CI, 1.26–1.56) and FOLFIRI plus AFL groups (hazard ratio, 1.34; 95% CI, 1.09–1.66). Among mCRC patients who were unresponsive to first-line FOLFOX plus anti-EGFR antibody [ 25 ], treatment durations of second-line irinotecan-based chemotherapy plus anti-VEGF agents were similar among the three groups (BEV, RAM, and AFL).…”

“…Two recent administrative claims database studies [ 24 , 25 ] addressed this issue: among mCRC patients who failed first-line chemotherapy with fluoropyrimidines and oxaliplatin plus BEV [ 24 ], the time to treatment failure, defined as the time from initial second-line chemotherapy to treatment termination due to any cause or death, was significantly longer in the FOLFIRI plus BEV group compared with that in the FOLFIRI plus RAM (hazard ratio, 1.40; 95% CI, 1.26–1.56) and FOLFIRI plus AFL groups (hazard ratio, 1.34; 95% CI, 1.09–1.66). Among mCRC patients who were unresponsive to first-line FOLFOX plus anti-EGFR antibody [ 25 ], treatment durations of second-line irinotecan-based chemotherapy plus anti-VEGF agents were similar among the three groups (BEV, RAM, and AFL). As the duration of second-line chemotherapy concomitant with anti-VEGF agent could be affected by the presence or absence of prior BEV therapy, discontinuation of second-line anti-VEGF treatment may be due to the exacerbation of toxicities; RAM discontinuation due to the occurrence of anti-VEGF related toxicities, including proteinuria, within 6 months was likely to occur in patients who received sequential RAM after BEV.…”

Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer

“…A retrospective report from Japan was also published [ 71 ]. An analysis of 1163 patients with wild-type RAS who were given anti-EGFR antibodies in first-line treatment was performed.…”

“…Cases in which patients received anti-EGFR antibodies in the first-line treatment are expected to receive angiogenesis inhibitors in second-line treatment. Two retrospective studies and one prospective study involving such patients described above seem to suggest the usefulness of angiogenesis inhibitors [ 70 , 71 , 72 ]. Historically, the results of these studies are similar to the data of BEV beyond progression [ 6 , 7 , 8 ].…”