Patient Demographics Details
A total of 51 patients from a single center in China received bevacizumab in addition to FOLFOX or cetuximab or both (cetuximab with FOLFOX). Most of the patients were older in age with thirty-one patients aged >50 years and had a median age of 54 years (range: 24-80 years). The median BMI of the overall population was 22.75 kg/m2. Most of the patients belonged to ECOG PS ≤1 (n=41) and AJCC II stage (n=34). Majority of the patients were on first line therapy of bevacizumab with cetuximab and FOLFOX (n=43, 84.31%) while remaining were on bevacizumab with FOLFOX (n=4) and bevacizumab with cetuximab (n=1). Patients on second line therapy of bevacizumab with cetuximab and FOLFOX were very few (n=3). The main site of disease was rectum for 28 patients, while colon was site of the disease in 23 patients. Forty-seven patients exhibited left sided primary tumor while 4 patients had right sided primary tumor. None of the patients had history of KRAS mutation. Out of the 51 patients, 19 patients had no history of BRAF mutation while it was unknown in 32 patients. The demographic and the clinical characteristics details of overall study population are shown in table 1.
Survival analysis of overall patient population
The 1-year PFS rates of all 51 patients was 76% while the 3-year PFS survival rate was not reached due to no CRC progression after current line of treatment. Ten patients showed progression after one year of first line of current treatment. The 1-year and 3-year OS rates for all 51 patients were 95% and 88%, respectively. The median duration of treatment was 23.5 weeks (range: 9 weeks to 51.8 weeks). The median OS and PFS for various demographic subgroup of patients were not reached. The Kaplan Meir survival analysis revealed no significant difference in demographics characteristics of patients including gender, age at diagnosis, site of disease, AJCC staging, BMI, site and side of primary tumor, line of current bevacizumab treatment and ECOG PS (Table 2).
Survival Analysis of Subgroups based on Demographics Characteristics
The univariate analysis for PFS revealed that bevacizumab with chemotherapy was more effective in males [HR (95% CI): 0.68 (0.2-2.4)], aged ≤50 years [HR 95% CI: 2 (0.52 – 7.8)], AJCC ≤ II stage, BMI ≤25 kg/m2 and rectum as main site of disease. There was no treatment difference between patients with ECOG PS ≤1 and ECOG PS>1. Addition of bevacizumab to cetuximab and FOLFOX treatment yielded better results than its addition to either cetuximab and FOLFOX regimen [HR (95% CI): 0.44 (0.094-2.1)]. However, no statistical significance was observed in any of these subgroups. Similarly, multivariate analysis for PFS revealed that bevacizumab with chemotherapy favoured male patients, aged ≤50 years, ECOG PS ≤1, rectum as the main site of disease, BMI ≤25 kg/m2 and combination with cetuximab and FOLFOX (Table 2).
The univariate analysis for OS revealed no significant difference across the various subgroups for patient demographics. Addition of bevacizumab therapy to chemotherapy resulted in more effective response in males [HR (95% CI): 0.65 (0.092-4.6)], aged >50 years [HR (95% CI): 0.21 (0.022-2)], AJCC ≤ II [HR (95% CI): 6.8 (0.7-65)], rectum as main site of disease [HR (95% CI): 0.23 (0.024-2.3)] and BMI ≤25 kg/m2 [HR (95% CI): 1.4 (0.14-13)]. The multivariate analysis for OS revealed favourable response in females, aged ≤50 years, AJCC ≤ II, rectum as main site of disease and BMI >25 kg/m2 (Table 2).
Survival Analysis based on First Line of Treatment
Log-rank tests comparing the OS and PFS for patients stratified based on demographic factors revealed no statistically significant difference in survival curves. PFS was marginally better in males [HR (95% CI): 0.64 (0.18-2.2)], aged ≤50 [HR (95% CI): 1.8(0.47-7)], ECOG PS ≤1[HR (95% CI): 0.95(0.2-4.5)], AJCC ≤ II [HR (95% CI): 0.92(0.24-3.5)], rectum as main site of disease [HR (95% CI): 0.61(0.17-2.1)], BMI ≤25 kg/m2 [HR (95% CI): 1.3(0.27-6)] and combination with cetuximab and FOLFIRI [HR (95% CI): 0.47(0.099-2.2)]. After adjusting for multiple variables, males, patients aged <60, with ECOG PS≤1, AJCC ≤II, BMI ≤25 and combination with cetuximab and FOLFIRI had marginally better PFS (Table 3).
OS was marginally better in males [HR (95% CI): 0.64(0.09-4.5)], aged >50 [HR (95% CI): 0.17(0.018-1.7)], rectum as main site of disease [HR (95% CI): 0.22(0.023-2.2)], BMI ≤25 [HR (95% CI): 1.3(0.13-12)]. After adjusting for multiple variables, patients aged >50, BMI >25 and rectum as site of disease had marginally better OS with bevacizumab (Table 3).
Safety in Overall Population as well as in First Line of Treatment
Toxicity was evaluated according to the WHO chemotherapeutic toxicity classification criteria (WHO criteria and Common Toxicity Criteria). Toxicities were usually observed in the acute stage, while late toxicity was rare. Fifteen patients (29.4%) reported grade I nausea and 26 patients (50.98%) with grade II nausea, 30 patients (58.82%) reported grade I neutropenia. Twenty-two patients (43.13%) experienced grade I vomiting while 15 patients (29.41%) reported hand and foot syndrome. Few patients reported other adverse events such as asthenia (7.84%) and palpitation (31.37%). No grade IV toxicity was observed. Toxicities associated with treatment with bevacizumab is reported in table 4.