Romera A, et al. - In patients with metastatic colorectal cancer, researchers compared the pharmacokinetic profile, effectiveness, safety, and immunogenicity of BEVZ92 (a proposed biosimilar to bevacizumab) with reference bevacizumab as a first-line treatment. BEVZ92 and reference bevacizumab are pharmacokinetically bioequivalent and do not show significant differences in effectiveness, immunogenicity and safety profiles in metastatic colorectal cancer patients in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI).

Methods

• A randomised, open-label trial was performed at 15 centres in Argentina, Brazil, India, Spain, and Ukraine.
• Eligibility criteria included patients who were aged 18 years or older, had metastatic colorectal cancer with at least one measurable non-irradiated lesion for which first-line chemotherapy was indicated and Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, had not received previous treatment for advanced disease, and whose bone marrow, hepatic, renal, and coagulation markers were all within normal ranges.
• For this investigation, study participants were randomly assigned (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.
• Randomisation was performed through a web service based on a stochastic minimisation 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.
• The primary endpoint was 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 population, which included all patients treated for whom serum concentration measurements were available during the first seven cycles.
• Bioequivalence was established if the 90% CIs for the BEVZ92 ratio to reference bevacizumab of the geometric means for AUC _0–336h and AUC _ss were within the acceptance interval of 80–125%.
• Objective response, clinical benefit, and progression-free survival in the intention-to-treat population and immunogenicity and safety profiles in all treated patients were included secondary endpoints.

Results

• In this analysis,142 patients were randomly assigned (71 to the BEVZ92 group and 71 to the reference bevacizumab group).
• Two participants assigned to BEVZ92 received no treatment (one withdrew consent, the other had a serious intestinal obstruction before starting treatment); therefore, 69 patients in the BEVZ92 group and 71 in the bevacizumab reference group were treated in the population.
• It was noted that the geometric mean ratio of AUC _0–336h in the BEVZ92 vs the control group was 99·4% (90% CI 90·5–109·0) and of AUC _ss was 100·0% (90·2–112·0).
• In the BEVZ92 and reference bevacizumab groups, 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 comparable.
• There were no relevant differences between the safety profiles of the two study treatments.
• The most common grade 3 or 4 adverse event reported in the BEVZ92 (14 [20%] of 69 patients) and reference bevacizumab (19 [27%] of 71 patients) groups was neutropenia.
• Researchers found serious adverse events in 19 (28%) patients in the BEVZ92 group and 21 (30%) in the reference bevacizumab group.
• Two patients died due to serious adverse events related to bevacizumab: sudden death in the BEVZ92 group and a serious large intestinal perforation in the reference bevacizumab group.
• The occurrence of anti-drug antibodies in both treatment groups was low and comparable (two patients in the BEVZ92 group and one in the reference bevacizumab group).