Retrospective Study Shows Bevacizumab Biosimilar Efficacy in NSCLC

Bevacizumab biosimilars were found to be as effective as the reference product in terms of progression-free survival (PFS) when combined with chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with advanced non–small cell lung cancer (NSCLC), according to a retrospective study.¹

This study was conducted to address the limited real-world data on the clinical efficacy of bevacizumab biosimilars in advanced NSCLC, a leading cause of cancer-related deaths globally, and its findings highlight that bevacizumab biosimilars are effective treatment options comparable to the reference product (Avastin), expanding access and reducing costs without compromising patient outcomes.

Lung cancer remains the leading cause of cancer-related deaths worldwide. Lung cancer is primarily classified into two types, with NSCLC accounting for 80% to 85% of cases and small cell lung cancer making up 10% to 15% | Image credit: mi_viri - stock.adobe.com

Lung cancer remains the leading cause of cancer-related deaths worldwide. Lung cancer is primarily classified into 2 types, with NSCLC accounting for 80% to 85% of cases and small cell lung cancer making up 10% to 15%.² While treatments like bevacizumab have shown improved outcomes in advanced NSCLC, real-world data on the efficacy of bevacizumab biosimilars in this setting are limited despite their potential to reduce costs and expand access to care.

The study retrospectively analyzed patients with stage IV non-squamous NSCLC treated at Taichung Veterans General Hospital, focusing on those receiving first-line combination therapy with bevacizumab (reference product or biosimilar). Patient inclusion required at least 3 cycles of anti-angiogenic therapy, with exclusions for mixed cancer types or second-line treatments.

From January 2020 to July 2022, 79 patients were enrolled in the study, including 59 treated with chemotherapy (CT) and 20 with TKIs, in combination with either the bevacizumab reference product (RP) or its biosimilar (BB).

These patients were divided into 4 subgroups:

1. CT-RP (n = 34)
2. CT-BB (n = 25)
3. TKI-RP (n = 9)
4. TKI-BB (n = 11)

The median age of the overall cohort was 60.4 years, with 60.8% being female, 64.6% never-smokers, and 86.1% having an ECOG performance status (PS) of 0 to 1. Nearly half of the patients (44.3%) had brain metastases, and 49.4% presented with malignant pleural effusion. There were no significant differences in baseline demographics or disease characteristics between the biosimilar and RP groups.

In the CT cohort, the median age was 61.5 years, with 61% female and 62.7% never-smokers. Most patients (62.7%) had stage 4B disease, and 71.2% received cisplatin-based regimens. The median PFS was 8.9 months for CT-BB and 6.9 months for CT-RP, with no significant difference (P = .255). The CT-BB group had an objective response rate (ORR) of 34.8% and a disease control rate (DCR) of 78.3%, similar to 41.2% ORR and 75.8% DCR in the CT-RP group. Tumor stage was the only variable significantly predicting PFS in this cohort, with patients at stage IVB facing higher risks of progression. The choice of bevacizumab product (BB or RP) did not significantly affect outcomes.

In the TKI cohort, the median age was 56.3 years, with 60% female and 70% never-smokers. Most patients (90%) had stage IVB disease. The median PFS was 13.6 months for TKI-BB and 18.4 months for TKI-RP, with no significant difference (P = .363). The TKI-BB subgroup achieved an ORR of 80% and a DCR of 90%, comparable to 71.4% ORR and 100% DCR in the TKI-RP subgroup. No predictors of PFS were identified in this group.

Adverse events were comparable between BB and RP subgroups. In the CT cohort, hypertension was reported in 52.5% and proteinuria in 39% of patients, with similar rates between CT-BB and CT-RP. Three cases of thrombosis were observed: 1 pulmonary embolism in each subgroup and one deep vein thrombosis in CT-RP. In the TKI cohort, hypertension occurred in 50% and proteinuria in 45% of patients, with no hemorrhage or thrombosis reported. Overall, the study found no significant differences in efficacy or safety profiles between the bevacizumab biosimilar and the reference product in either the CT or TKI cohorts.

The study's limitations include its retrospective design, small sample size, limited generalizability due to a single-center, Taiwanese-only patient population, lack of standardized criteria for choosing between reference product and biosimilar, and inability to analyze the 15 mg/kg bevacizumab dosage.

“With patents expiring, the development of biosimilars not only ensures similar clinical treatment efficacy but also has the potential to reduce healthcare expenditure…." the authors concluded. "Biosimilars help to reduce medical expenses and also expand access to treatment for patients with cancer…. Therefore, we believe that opting for the lower dosage did not compromise our treatment outcomes.”

References

1. Ou W-F, Hsu K-H, Tseng J-S, et al. Real-world clinical efficacy of bevacizumab biosimilar in patients with advanced non-small-cell lung cancer. Ther Adv Med Oncol. Published online October 17, 2024. doi:10.1177/17588359241290718

2. Key statistics for lung cancer. American Cancer Society. Updated January 29, 2024. Accessed November 26, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=Most%20lung%20cancer%20statistics%20include,%25%20to%2085%25%20are%20NSCLC