Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non–small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study

Abstract

Purpose: This phase III study compared clinical efficacy and safety of the biosimilar ABP 215 with bevacizumab reference product (RP) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Patients and Methods: Patients were randomized 1:1 to ABP 215 or bevacizumab 15 mg/kg every three weeks for 6 cycles. All patients received carboplatin and paclitaxel every three weeks for !4 and 6 cycles. The primary efficacy endpoint was risk ratio of objective response rate (ORR); clinical equivalence was confirmed if the 2-sided 90% confidence interval (CI) of the risk ratio was within the margin of 0.67 to 1.5. Secondary endpoints included risk difference of ORR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS); pharmacokinetics, adverse events (AEs), and incidence of antidrug antibodies (ADAs) were monitored. Results: A total of 820 patients were screened; 642 were randomized to ABP 215 (n ¼ 328) and bevacizumab (n ¼ 314). Overall, 128 (39.0%) and 131 (41.7%) patients in the ABP 215 and bevacizumab groups, respectively, had objective responses [ORR risk ratio: 0.93 (90% CI, 0.80-1.09)]. In the ABP 215 and bevacizumab group, 308 (95.1%) and 289 (93.5%) patients, respectively, had at least 1 AE; 13 (4.0%) and 11 (3.6%) experienced a fatal AE. Anti-VEGF toxicity was low and comparable between treatment groups. At week 19, median trough serum drug concentration was 132 mg/mL (ABP 215 group) and 129 mg/mL (bevacizumab group). No patient tested positive for neutralizing antibodies. Conclusions: ABP 215 is similar to bevacizumab RP with respect to clinical efficacy, safety, immunogenicity, and pharmacokinetics. The totality of evidence supports clinical equivalence of ABP 215 and bevacizumab.

Biosimilars as a Future, Promising Solution for Financial Toxicity: A Review with Emphasis on Bevacizumab

“…Similar outcomes are also reported between ABP-125 and the bevacizumab reference product in the treatment of advanced non-small-cell lung cancer in a phase III trial (the MAPLE study), conducted in Canada from 2015-2018 [23]. This randomized, double-blind, phase III comparative trial showed a response rate risk ratio of 0.93 with a 90% confidence interval (CI) between 0.80-1.09, which was similar for both Avastin and bevacizumab ABP-125 meeting the primary endpoint [23].…”

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

“…Whereas PFS and OS may be influenced by factors such as tumor burden and subsequent lines of therapy, ORR is a direct measure of drug antitumor activity and hence is considered a sensitive endpoint for detecting potential product-related differences between a biosimilar and reference product [29, 30]. Indeed, ORR has been used as the primary endpoint in comparative clinical studies of other oncology biosimilars [31–34]. Additionally, bevacizumab plus paclitaxel and carboplatin has a well-characterized safety and efficacy profile as first-line therapy for patients with advanced non-squamous NSCLC [8].…”

“…Addressing escalating healthcare costs and improving patient access to treatment remain priorities in the treatment of cancer, and biosimilars are expected to have a key role [17, 18]. In addition to PF-06439535, several potential bevacizumab biosimilars are in clinical development, and in most instances confirmatory clinical studies have been conducted in patients with advanced non-squamous NSCLC [31, 40]. Furthermore, the bevacizumab biosimilar ABP 215 has been licensed in the US and authorized in the EU [41, 42].…”

NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 1.2020

“…Bevacizumab biosimilars may be used in any of the systemic therapy regimens containing bevacizumab (eg, ABCP) that are used for eligible patients with metastatic NSCLC based on clinical data and FDA approvals. [30][31][32][33][34] However, a specific bevacizumab biosimilar should be used for the entire regimen, including maintenance therapy, and should not be substituted in the middle of therapy.…”