Bevacizumab and Biosimilar SB8 Demonstrate Similar Outcomes in Metastatic or Recurrent NSCLC

In terms of best objective response rate (ORR) ratio, bevacizumab and SB8 appeared equivalent with comparable safety, pharmacokinetics, and immunogenicity as treatment of patients with metastatic or recurrent nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 randomized study (NCT02754882).

The survival outcomes observed in this study further supported the biosimilarity between bevacizumab and SB8.

The double-blind multicenter equivalence study was conducted across 100 different sites in 13 countries, in which 763 patients were randomized 1:1 to receive either bevacizumab (n = 384) or SB8 (n = 379) concurrently given with paclitaxel or carboplatin, and they were stratified by age group and gender. Patients who experienced a complete response (CR), partial response (PR), or stable disease (SD) after completion of the induction period were enrolled to the maintenance period, in which either treatment was administered until progressive disease, unacceptable toxicity, death, or the end of the study. The median follow-up duration was 15.2 months (range, 0-24.4).

The mean number of cycles in SB8 arm was 4.8 during the induction period versus 4.8 in the bevacizumab arm, and the mean cycles of paclitaxel were 4.8 in the SB8 arm versus 4.8 in the bevacizumab arm. During the maintenance period, the mean number of cycles was 9.3 in the SB8 arm and 9.1 in the bevacizumab arm.

In the overall population, the proportion of patients that achieved a best ORR was 47.6% in the SB8 group and 42.8% in the bevacizumab group. The risk ratio of best ORR was 1.11 (90% CI, 0.975-1.269), which was contained with the predefined equivalence margin (range, 0.737-1.357). In the per protocol set, the proportion of patients who achieved the best ORR was 50.1% in the SB8 arm and 44.8% in the bevacizumab arm, and the risk difference was 5.3% (95% CI, -2.2-12.9). The lower margin was also contained to the predefined equivalence margin, and the upper margin was outside of the equivalence margin.

In the full analysis set, only 1 patient achieved a CR in the bevacizumab arm, whereas PRs were achieved by 172 (45.4%) in the SB8 arm and 151 (39.4%) in the bevacizumab arm. SD was achieved by 136 (35.9%) of patients in the SB8 arm and 151 (39.4%) in the bevacizumab arm, while progressive disease was observed in 27 (7.1%) and 21 (5.5%), respectively. Forty-three patients in the SB8 arm and 58 in the bevacizumab arm were not evaluable in this overall population.

In the per protocol set of patients, only 1 again had a CR in the bevacizumab arm versus none in the SB8 arm, PRs were observed in 169 (50.1%) versus 146 (44.5%), SD in 134 (39.8%) versus 149 (45.4%), and progressive disease in 25 (7.4%) and 20 (6.1%), respectively. In this population, 9 patients in the SB8 arm and 12 in the bevacizumab arm were not evaluable.

The median progression-free survival (PFS) was 8.50 months (95% CI, 7.40-9.70) in the SB8 arm versus 7.90 (95% CI, 7.40-9.50) in the bevacizumab arm (HR, 0.99; 95% CI, 0.83-1.18). The 12-month PFS rate was 34% (95% CI, 29%-40%) in the SB8 arm and 30% (95% CI, 25%-35%) in the bevacizumab arm.

Overall, 166 (43.8%) patients in the SB8 arm and 171 (44.6%) in the bevacizumab arm had died. The median overall survival (OS) was 14.90 months (95% CI, 13.30-17.10) in the SB8 arm and 15.80 months (95% CI, 13.60-17.10) in the bevacizumab arm (HR, 1.03; 95% CI, 0.83-1.28), and the 12-month OS rate was 61% (95% CI, 56%-66%) and 62% (95% CI, 57%-67%), respectively. The median duration of response was 7.70 months (range, 6.00-8.30) in the SB8 arm and 7.00 months (range, 6.10-8.30) in the bevacizumab arm (HR, 1.05; 95% CI, 0.81-1.37).

The PFS, OS, and duration of response findings appeared consistent between both the full analysis and per protocol sets.

Treatment-emergent adverse events (TEAEs) occurred in 348 patients (92.1%) in the SB8 arm and 346 (91.1%) in the bevacizumab arm, which were mostly grades 1 or 2. The most common TEAEs in the SB8 versus bevacizumab arms, respectively, included alopecia (48.7% vs. 48.2%), anemia (24.3% vs. 23.7%), and nausea (19.6% vs. 21.1%), and the most common TEAEs of grade 3 or higher included neutropenia (8.7% vs. 9.5%), hypertension (6.3% vs. 3.7%), anemia (4.8% vs. 5.5%), and decreased neutrophil count (4.0% vs. 3.2%).

Serious TEAEs occurred in 75 (19.8%) patients in the SB8 arm versus 81 (21.3%) in the bevacizumab arm, and TEAEs led to treatment discontinuation in 50 (13.2%) versus 36 (9.5%) while death occurred in 22 (5.8%) versus 27 (7.1%), respectively.

Overall, the safety profile of SB8 was comparable to that of bevacizumab in this study. The efficacy and pharmacokinetics were also comparable between the 2 arms in the trial.

Overall, the baseline demographics and disease characteristics were well balanced between the 2 arms. The majority of patients were male (66.6%) overall, and the median age was 60.1 years. Additionally, 91.1% of the overall population in the study was Caucasian, and the majority had an ECOG performance status of 1 (72.0%). The most common cancer type was adenocarcinoma (95.3%), and the majority had stage IV disease (99.0%).

To be included in the study, patients had to have an ECOG performance status of 0 or 1, a histologically or cytologically confirmed metastatic or recurrent nonsquamous NSCLC, at least 1 measurable lesion, and at least 3 months life expectancy. Patients were not able to enroll if they had EGFR mutations or ALK gene rearrangements, symptomatic brain metastasis or leptomeningeal disease, or a history of frontline systemic therapy for metastatic/recurrent NSCLC, systemic neoadjuvant/adjuvant chemotherapy ≤12 months prior to randomization. They also could not have received a VEGF receptor or EGFR signaling pathways.

_Reference

_{Reck M, Luft A, Bondarenko I, et al. A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer. Lung Cancer. 2020. 146;12-18. doi: 10.1016/j.lungcan.2020.05.027}