Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

Abstract

Angiogenesis inhibitors are of considerable interest for treating metastatic colorectal cancer (mcRc). This trial evaluated the efficacy and safety of apatinib in chemotherapy-refractory mCRC. Apatinib 500 mg was administered daily to patients who had progressed after two or more lines of standard fluorouracil-based chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Overall, 48 patients were enrolled. ORR and DCR were 8.3% (4/48) and 68.8% (33/48), respectively. Median PFS and OS were 4.8 (95% confidence interval [CI], 3.653-5.887) and 9.1 months (95% CI, 5.155-13.045), respectively, and did not differ between subgroups stratified by previous anti-angiogenic therapies. The most prevalent grade 3-4 adverse events were hypertension (12.5%), hand-foot syndrome (HFS, 10.4%), thrombocytopenia (10.4%), and proteinuria (8.3%). Low baseline neutrophil/lymphocyte ratio (NLR, hazard ratios [HR], 0.619; P = 0.027), early carbohydrate antigen 19-9 (CA19-9) decrease (HR, 1.654; P = 0.016), and HFS (HR, 2.087; P = 0.007) were associated with improved PFS. In conclusion, apatinib monotherapy demonstrated encouraging efficacy with manageable toxicities in chemotherapy-refractory mcRc. previous anti-angiogenic therapies did not influence outcomes. Baseline NLR, early CA19-9 decrease, and HFS could predict the efficacy of apatinib. Colorectal cancer (CRC) remains the third leading cancer globally 1 , and approximately 40-50% patients present with advanced disease at diagnosis 2. Until recently, the standard of care for patients in this setting has been regorafenib or trifluridine/tipiracil (TAS102) after the progression of fluoropyrimidine-based chemotherapy with

<p>Up-and-Coming Experimental Drug Options for Metastatic Colorectal Cancer</p>

“…13 These results are corroborated by additional smaller studies in mCRC including Guo and colleagues, (PFS 3.8 months, OS not reached), Liang and colleagues, (PFS 4.8 months, OS 10.1 months), and Li and colleagues, (PFS 3.7 months, OS 7.3 months). [13][14][15][16] Adverse effects from rivoceranib were consistent with inhibitors of the VEGF pathway and included hypertension, proteinuria, and hand-foot syndrome. 3,13 A multicenter phase I/II trial is underway in the United States further evaluating the rivoceranib in mCRC (NCT04073615).…”

“…13 Additionally, rivoceranib exceeded the historical median PFS (1.7 months) and OS (6.3 months) for best supportive therapy in the third-line and beyond for mCRC. 13 These results are corroborated by additional smaller studies in mCRC including Guo and colleagues, (PFS 3.8 months, OS not reached), Liang and colleagues, (PFS 4.8 months, OS 10.1 months), and Li and colleagues, (PFS 3.7 months, OS 7.3 months). [13][14][15][16] Adverse effects from rivoceranib were consistent with inhibitors of the VEGF pathway and included hypertension, proteinuria, and hand-foot syndrome.…”

“… 3 , 4 It has been hypothesized that intracellular targeting of VEGFR-2 may overcome resistance to bevacizumab, which solely targets the ligand. 13 Rivoceranib was studied in a Phase I trial of 46 patients with advanced solid malignancies naïve to VEGF inhibition. 3 Of the 36 evaluable patients for response, 7 (18.9%) had a partial response (PR), including 3 patients with colon cancer.…”

Previous Use of Anti-Vascular Endothelial Growth Factor Receptor Agents Decreases Efficacy of Fruquintinib in Metastatic Colorectal Cancer Refractory to Standard Therapies

“…First, bevacizumab combined with chemotherapy is recommended as standard therapy for mCRC (3), but the impact of prior bevacizumab on later treatment is still unclear. Retrospective and prospective studies (22,23) regarding the efficacy of apatinib in mCRC revealed no significant differences between patients with or without prior treatment with bevacizumab in PFS and OS. Besides, clinical trials (10,11) evaluating the efficacy of fruquintinib did not exclude patients with previous use of bevacizumab.…”

“…These results were confirmed in the CONCUR trial (median PFS: 3.2 vs. 1.7 months, P < 0.0001; median OS: 8.8 vs. 6.3 months, P = 0.00016; respectively) (6). A recent prospective study of apatinib also showed efficacy in chemotherapy-refractory mCRC with median PFS and OS of 4.8 months (95% CI, 3.653-5.887 months) and 9.1 months (95% CI, 5.155-13.045 months), respectively (22). In the present study, we retrospectively explored the efficacy of the newly approved VEGFR inhibitor, fruquintinib, and observed shorter median PFS (3.1 vs. 3.7 months) and OS (8.6 vs. 9.3 months) compared with the FRESCO trial.…”