Study Shows Biosimilarity of Bevacizumab Biosimilar in CRC

Patients with metastatic colorectal cancer (mCRC) experienced comparable safety and efficacy when administered bevacizumab biosimilar Encode compared with patients who received reference bevacizumab (Avastin) when the drug was used as a first-line treatment, according to a comprehensive real-world study.1

CRC ranks among the most prevalent and fatal cancers globally, with most cases progressing to mCRC, where treatments targeting vascular endothelial growth factor (VEGF), such as bevacizumab (Avastin), have become the standard of care in combination with chemotherapy. In 2024, the US was projected to see approximately 152,810 new cases of CRC and 53,010 deaths, making it the second most common cause of combined cancer-related deaths.2 Although incidence and death rates have declined in older adults due to improved screening, early detection, and treatment, rates among those younger than 55 yeras have been rising steadily since the mid-1990s and mid-2000s, respectively.

Encoda, which was approved in China in 2019, offers a cost-effective alternative, reducing patient costs and health care expenditure through market competition. While its approval for mCRC relied on indication extrapolation, the present study, published in Clinical Medicine Insights: Oncology, was the first to compare the efficacy and safety of Encoda and bevacizumab in mCRC, aiming to confirm their equivalence and address existing gaps in clinical evidence.

The multicenter, real-world observational study was conducted at 2 institutions in China and included patients who had histologically confirmed mCRC, an Eastern Cooperative Oncology Group performance status of 2 or lower, and received backbone chemotherapy combined with Encoda or reference bevacizumab as first-line therapy between April 2021 and December 2022. Patients were excluded if they refused to participate or had taken part in other studies within the past 4 weeks. Data were collected both prospectively and retrospectively. Treatments lasted up to 12 cycles, followed by maintenance therapy with Encoda or the originator until disease progression, intolerable adverse events, or eligibility for surgery or radiation therapy.

The primary end point was the overall response rate (ORR). The secondary end point was progression-free survival, defined as the time to disease progression, death, or last follow-up. The safety end point compared treatment-emergent adverse events between Encoda and reference bevacizumab. Clinical equivalence was assessed through ORR risk ratios and differences, with predefined equivalence ranges set by regulatory agencies, including the Chinese National Medical Products Administration (NMPA), the FDA, and the European Medicines Agency (EMA).

The study enrolled 436 patients, with 234 receiving the bevacizumab biosimilar (Encoda) and 202 receiving reference bevacizumab, both combined with backbone chemotherapy. The median age was 60 years, and most patients were male (59.2%). Over half of the patients (53.2%) had metastases at 1 site without peritoneal involvement. KRAS mutations were observed in 56.9% of patients, and most (84.6%) exhibited proficient mismatch repair. The most prevalent concomitant conditions were hypertension (23.9%) and diabetes (11.9%).

Efficacy analysis showed comparable outcomes between the 2 treatment groups. In the Encoda group, 2 patients achieved a complete response (CR) and 97 achieved a partial response (PR), resulting in an ORR of 42.3% (95% CI, 35.9%-48.9%). In the reference bevacizumab group, 1 patient achieved CR and 84 achieved PR, with an ORR of 42.1% (95% CI, 35.2%-49.2%). The ORR risk ratio of 1.005 and the ORR risk difference of 0.002 were within the equivalence ranges defined by regulatory agencies (FDA, NMPA, EMA), confirming clinical comparability between Encoda and reference bevacizumab.

Other response categories, including stable disease and progressive disease, were also similar across groups, reinforcing that the efficacy of the biosimilar was equivalent to the reference product.

Limitations of the study included its reliance on electronic health records, which may omit relevant data, and the relatively small sample size. Larger-scale studies were recommended to validate these findings further. Nonetheless, the marginal differences in safety and efficacy support the use of Encoda as a cost-effective alternative to bevacizumab, providing valuable insights for clinical oncologists and patients managing mCRC.

References

1. Shan H, Wang M, Huang S, et al. Efficacy and safety of bevacizumab biosimilar (Encoda) compared with reference bevacizumab (Avastin) in patients with metastatic colorectal cancer: a multicenter, real-world study. Clin Med Insights Oncol. Published December 11, 2024. doi:10.1177/11795549241303726

2. Keystatistics for colorectal cancer. American Cancer Society. Updated January 29, 2024. Accessed December 13, 2024. https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html