Romera A, et al. - The researchers compared the pharmacokinetic contour, efficiency, safety, and immunogenicity of BEVZ92 with reference bevacizumab as a first-line treatment in metastatic colorectal cancer cases. BEVZ92 and reference bevacizumab were observed pharmacokinetically bioequivalent. They found no significant variations in effectiveness, immunogenicity, and safety outlines when prescribed in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI).

Methods

• In Argentina, Brazil, India, Spain, and Ukraine, the researchers did a randomised, open-label trial at 15 centres.
• Subjects of age 18 years or older who had metastatic colorectal cancer with at least one assessable non-irradiated lesion for which first-line chemotherapy was indicated and Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, were not given previous treatment for advanced disease, and whose bone marrow, hepatic, renal, and coagulation markers were all within the normal limits.
• They randomly assigned the subjects(1:1) to either BEVZ92 or reference bevacizumab (5 mg/kg on day 1 of each cycle every 2 weeks) in combination with FOLFOX or FOLFIRI.
• Randomization was done through a web service based on a stochastic minimization algorithm and was stratified by chemotherapy regimen (FOLFOX vs FOLFIRI), previous adjuvant therapy (yes vs no), ECOG performance status (0–1 vs 2), and study site.
• They considered primary endpoint, the area under the concentration-vs-time curve after a single infusion (AUC_0-336h) and at steady state (AUC_ss)—ie, at cycle 7—in the assessable community, which involved all treated cases for whom serum concentration measurements were available during the first 7 cycles.
• Bioequivalence was established if the 90% CIs for the ratio of BEVZ92 to reference bevacizumab of the geometric means for AUC_0-336h and AUC_ss were within the permissible interval of 80–125%.
• Objective response, clinical benefit, and progression-free survival in the intention-to-treat population and immunogenicity and safety profiles were included as secondary endpoints in all treated participants.

Results

• They randomly assigned 142 individuals, 71 to the BEVZ92 group and 71 to the reference bevacizumab group.
• The treated population comprised 69 patients in the BEVZ92 group and 71 in the reference bevacizumab group because two participants assigned to BEVZ92 did not receive treatment (one withdrew consent, the other had a serious intestinal obstruction before starting treatment).
• The geometric mean ratio of AUC_0-336h in the BEVZ92 vs the control group was observed 99·4% (90% CI 90·5–109·0) and of AUC_ss was 100·0% (90·2–112·0).
• Objective response (35 [49%] of 71 vs 40 [56%] of 71), clinical benefit (62 [87%] vs 65 [92%]), and progression-free survival (median 10·8 months [95% CI 7·4–11·5] vs 11·1 months [95% CI 8·0–12·8]) were assessed similar in the BEVZ92 and reference bevacizumab groups.
• They noted no significant differences between the safety profiles of the two study treatments.
• The most common grade 3 or 4 adverse emergency reported in BEVZ92 (14 [20%] of 69 patients) and reference bevacizumab (19 [27%] of 71 patients) groups was neutropenia.
• Serious adverse events were observed in 19 (28%) persons in the BEVZ92 group and 21 (30%) in the reference bevacizumab group.
• Bevacizumab-related serious adverse events caused death of 2 individuals: A sudden death in the BEVZ92 group and a serious large intestinal perforation in the reference bevacizumab group.
• There was similar but low occurrence of anti-drug antibodies in both the treatment groups (2 patients in the BEVZ92 group and 1 in the reference bevacizumab group).