Among the data that supported the biosimilar’s approval was a phase 3 study in patients with advanced nonsquamous non–small cell lung cancer. This week, researchers published detailed findings from that study.
Last month, the FDA approved Pfizer’s Zirabev, a bevacizumab biosimilar referencing Avastin, for the treatment of metastatic colorectal cancer, recurrent or metastatic nonsquamous non—small cell lung cancer (NSCLC), recurrent glioblastoma, metastatic renal cell carcinoma, and persistent, recurrent, or metastatic cervical cancer. The biosimilar was also approved in the European Union earlier in the year.
Among the data that supported the biosimilar’s approval was a phase 3 study in patients with advanced nonsquamous NSCLC. This week, researchers published detailed findings from that study. The paper, appearing in BioDrugs, reports on the study of the biosimilar in comparison with EU-licensed reference bevacizumab based on objective response rate (ORR) in patients treated with the biosimilar or the reference in the first-line setting.
The study was conducted at 159 centers in 27 countries among adult patients with confirmed, newly diagnosed stage IIIB or IV NSCLC or recurrent NSCLC. In total, 719 patients were randomized between 2015 and 2016 to receive the biosimilar (n = 358) or the refence (n = 361) plus paclitaxel and carboplatin. After chemotherapy was discontinued, patients could receive bevacizumab monotherapy. When the study completed in 2017, the extent of exposure between treatment groups was similar.
In total, 45.3% (95% CI, 40.01%-50.57%) of patients in the biosimilar arm and 44.6% (95% CI, 39.40%-49.89%) of patients in the reference arm achieved an objective response by week 19 that was later confirmed by week 25.
The unstratified ORR risk ratio was 1.015 (95% CI, 0.863-1.193; 90% CI, 0.886-1.163), and the unstratified ORR risk difference was 0.653% (95% CI,  6.608%-7.908%). These CIs fell within the equivalence margins prespecified by regulatory authorities in the United States, European Union, and Japan.
Analysis of survival and duration of response (DOR) was also conducted. The estimated probability of remaining progression-free at 1 year was 33.1% in the biosimilar arm and 30.9% in the reference arm. The probability of maintaining response for 1 year was 33.8% in the biosimilar arm and 30.8% in the reference arm. The estimated median DOR was 8.3 months (95% CI, 7.3-10.0) in the biosimilar arm and 6.6 months (95% CI, 6.2-8.3) in the reference arm.
In the safety population, 96.6% of patients in the biosimilar arm and 96.9% of patients in the reference arm experienced at least 1 adverse event (AE). The most frequently reported AEs were alopecia and anemia. Six patients in the biosimilar group died; 3 of the deaths were considered to be related to paclitaxel and carboplatin. One patient in the reference arm died.
The incidence of immunogenicity was low; 1.5% of patients in the biosimilar arm and 1.4% of patients in the reference arm tested positive for antidrug antibodies (ADAs). All ADAs were low-titer. No patients in the biosimilar arm had neutralizing antibodies, and 3 patients in the reference group had neutralizing antibodies.
The authors conclude that the biosimilar demonstrated similarity to the EU reference in patients with advanced NSCLC, and no notable differences were observed between groups. These results, they say, confirm earlier clinical studies of the biosimilar in comparison with the reference.
Reinmuth N, Bryl M, Bondarenko I, et al. PF-06439535 (a bevacizumab biosimilar) compared with reference bevacizumab (Avastin), both plus paclitaxel and carboplatin, as first-line treatment for advanced non-squamous non—small-cell lung cancer: a randomized, double-blind study [published online July 23, 2019]. BioDrugs. doi: 10.1007/s40259-019-00363-4.