Results from Phase 3 Trial Show Similar Efficacy and Safety Outcomes with CT-P16 versus Bevacizumab in Patients with NSCLC

One-year follow-up data from a phase 3 study found similar duration of response, time to progression (TTP), and survival rates with the biosimilar candidate CT-P16 compared with its reference drug, bevacizumab (Avastin), in the first-line treatment of patients with metastatic or recurrent nonsquamous non–small-cell lung cancer (NSCLC). These findings were presented by Claire Verschraegen, MD, Director, Division of Medical Oncology, and Diane Nye and Michael Rayden Chair in Innovative Cancer Research, The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues during a poster session at the European Society for Medical Oncology Congress 2022.

Pharmacokinetic equivalence between CT-P16 and bevacizumab was demonstrated previously in a phase 1 study, with similar safety and immunogenicity profiles. Therapeutic equivalence was also shown based on objective response rate and best overall response during the induction period of the study from which the follow-up data were reported.

Study Details

The double-blind, randomized, multicenter, phase 3 trial enrolled 689 patients with stage IV metastatic or recurrent nonsquamous NSCLC. Patients were randomized in a 1:1 ratio to CT-P16 (N = 342) or bevacizumab (N = 347) in combination with carboplatin and paclitaxel for up to 6 cycles (induction period), followed by a maintenance period of CT-P16 or the reference product as monotherapy until disease progression or intolerable toxicity.

During the induction period, the complete response rates were 0.6% in patients randomized to CT-P16 versus 0.9% in those randomized to bevacizumab. The partial response rates were 41.8% and 41.2%, respectively. The response rates were within the equivalence margins established.

In terms of duration of response, the percentage of patients with events was 72.7% in the CT-P16 arm versus 74.7% in the bevacizumab arm, and the median time to response was 7.2 and 6.3 months, respectively.

Regarding TTP, the percentage of patients with events was 54.4% and 54.2% in the CT-P16 and reference product arms, respectively, and the median TTP was 8.5 and 8.3 months, respectively.

The percentage of patients with a progression-free survival (PFS) event was 72.5% and 70.9% in the CT-P16 and bevacizumab arms, respectively, and the median PFS was 7.9 and 7.2 months, respectively, for a hazard ratio (HR) of 0.92 (95% confidence interval [CI], 0.77-1.10).

The percentage of patients with an overall survival (OS) event was 48.0% and 48.4% in the CT-P16 and reference product arms, respectively, and the median OS was 17.1 and 15.6 months, respectively, for an HR of 0.95 (95% CI, 0.77-1.19).

A total of 332 (96.2%) patients in the CT-P16 arm and 320 (93%) in the bevacizumab arm experienced at least 1 treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or grade 2. The number of grade ≥3 TEAEs was similar between the 2 arms (43.8% in the CT-P16 arm vs 41.9% in the reference product arm). The most frequently reported TEAEs in both treatment arms were alopecia (63.8% vs 63.4% in the CT-P16 and reference product arms, respectively) and anemia (31.6% vs 27.0%, respectively). Some 6.7% in the CT-P16 arm and 7.0% in the bevacizumab arm had at least 1 TEAE that led to death.

Immunogenicity was similar between the 2 arms. The percentage of patients with antidrug antibodies during the study was 22.6% and 24.1% in the biosimilar and reference product arms, respectively, and the percentage who were neutralizing antibody–positive during the study was 2.3% in each arm.

The researchers concluded that the time-to-event analysis up to 1 year from the time of enrollment of the last patient in the study was comparable between CT-P16 and bevacizumab in terms of duration of response, TTP, PFS, and OS. The safety profile was also similar between the 2 agents.

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