Planchard, Pegram Review Evidence for Samsung Bioepis Biosimilars

Recent clinical and real world evidence for Samsung Bioepis biosimilars for bevacizumab and trastuzumab support use of these products in place of the reference versions, David Planchard, MD, and Mark D. Pegram, MD, said at the European Society for Medical Oncology Congress Virtual 2020, in a review of study findings.¹

“People may know that biosimilars save money overall, but want to see that the data prove clinical similarity in a very controlled setting as well as in the real world,” said David Planchard, MD, of Institut Gustave Roussy (IGR) in Villejuif, France. Planchard serves as associate professor of medicine with the Thoracic Tumor Board at IGR.

The Samsung Bioepis bevacizumab biosimilar Aybintio (SB8) was approved in August for marketing by the European Commission. Samsung Bioepis’ trastuzumab biosimilar Ontruzant was launched in the United States in April.

Planchard noted that SB8 and the bevacizumab reference product (Avastin, BEV) have an “identical primary amino acid sequence and have demonstrated highly similar structural, physiochemical and biological properties.” A phase 3 trial randomized 763 patients with non–small cell lung cancer roughly equally to SB8 and BEV.^1,2 Of those, 258 completed induction treatment with SB8 and 277 with BEV. The mean age of patients was 60.2 vs 60 in the respective arms.

In the full analysis set (FAS), equivalence was demonstrated in terms of best overall response rate (ORR) risk ratio and risk difference. The ORR in the FAS was 47.6% for SB8 vs 42.8% for BEV. In the per protocol set (PPS), the best ORR was 50.1% for SB8 vs 44.8% for BEV.

Median progression-free survival (PFS) in the FAS was 8.5 months for SB8 vs 7.9 months for BEV, and in PPS the median PFS was 8.5 months vs 7.9 months, respectively. Median overall survival (OS) in the FAS was 14.9 months vs 15.8 months, respectively; and in PPS, 14.8 months vs 15.8 months. Mean duration of response was 6.38 months vs 6.79 months, respectively, in the FAS; and 6.33 months vs 6.81 months in PPS.

Tumor burden change at 24-weeks from start of induction therapy in FAS was 0.6% (95% CI, –4.18% to 2.99%).

Overall responses also helped to demonstrate comparative efficacy in the trial arms. At cycle 2, there were 96 (28.5%) partial responses (PRs) in the SB8 group vs 88 (26.8%) in the BEV group; and stable disease was achieved by 202 (59.9%) and 201 (61.3%), respectively.

By cycle 6, the numbers were still close, demonstrating comparability. There were 97 (57.1%) and 83 (49.4%) PRs, respectively; and 60 (35.3%) and 70 (41.7%) SDs, Planchard said. At cycle 6, there was 1 (0.6%) complete response in the BEV group.

In terms of treatment emergent adverse events of special interest, proteinuria was observed in 2 instances in the SB8 arm (0.5%) and 7 patients (1.8%) in the BEV group. Hypertension was noted in 29 (7.7%) and 16 (4.2%) of each group, respectively.

Pharmacokinetic profiles also were highly comparable, Planchard said.

Pegram, director of the Breast Cancer Oncology Program at Stanford Women’s Cancer Center, Stanford University Cancer Institute, California, discussed real world data for biosimilar trastuzumab (SB3, Ontruzant) plus reference pertuzumab in early stage breast cancer.

He noted that a 56% pathological complete response rate (pCR) was noted in 215 Danish patients with HER2-positive breast cancer who received neoadjuvant chemotherapy plus SB3 plus pertuzumab, which he said was exactly comparable to historical trial evidence for the reference drug (Herceptin).

“Indeed, 68% of patients treated in the neoadjuvant setting with node-positive disease converted from lymph node–positive disease to lymph node–negative disease after treatment, so that’s also very reassuring and demonstrates the activity of this trastuzumab biosimilar when combined with pertuzumab,” he said.¹

In a separate study involving real-world outcomes of 35 patients from Austria with HER2-positive breast cancer who received chemotherapy plus SB3 plus pertuzumab, the safety and efficacy profile of SB3 plus pertuzumab was consistent with that of the reference product in that combination. Significantly, 22 patients treated in the neoadjuvant setting achieved a pCR of 50%; none of the 35 patients had a decline in left ventricular ejection fraction (LVEF) of more than 10%; and 2 patients had an LVEF decline of ≤ 5% after treatment. “This is also very reassuring in terms of cardiac safety signals,” Pegram said.¹

Importantly, Pegram said, “this recent real-world evidence supports the extrapolation of trastuzumab-dttb [SB3] to include combination [therapy] with pertuzumab.”

Reference

1. Planchard D, Pegram MD. Navigating the optimized oncology treatment options in colorectal cancer, lung cancer and breast cancer through multidisciplinary discussions: clinical evidences of biosimilars. Presented at: ESMO Congress Virtual 2020. 5389.

2. 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.