Bevacizumab’s Benefit in Colorectal Cancer May Be Limited to 2 Years Post-Administration
The 2-year benefit of bevacizumab in colorectal cancer may explain why survival benefits are seen in studies with two-year, but not longer, follow-ups.
A study found Avastin's benefits for colorectal cancer may last around 2 years, explaining survival improvements seen in some trials.
The benefits of bevacizumab (Avastin) for the treatment of patients with colorectal cancer (CRC) appear to persist for approximately 2 years after its first administration, which may explain the survival benefit of the drug seen in studies with a median follow-up of 24 months but not in those with follow-ups beyond 30 months, a recent study found.
Findings from this review, which were presented at the 2025 ASCO Gastrointestinal Cancers Symposium, also demonstrated that this may also explain the crossover of survival curves in the PARADIGM trial (NCT02394795), in addition to the benefits of bevacizumab in patients with high tumor burden, short survival, and those treated in the second- and third-line setting for CRC.
In this review, researchers analyzed data from several studies in addition to PARADIGM, including FIRE-3 (NCT00433927), CALGB 80405 (NCT00265850), PEAK (NCT00819780), AVANT (NCT00112918), and NSABP-08 (NCT00096278).
Based on findings from the NSABP-08 trial, bevacizumab was shown to reduce the time to relapse for 6 months, although this effect diminished and was lost at the 12-month mark. Twenty-four months after bevacizumab’s first administration, the risk for relapse increased steadily in patients treated with the drug compared with the control.
Researchers observed identical kinetics in the AVANT study in patients with metastatic ovarian cancer, suggesting that the time-related effects of the drug were seen regardless of disease type.
“The biologic explanation of the clinical data is that short-term treatment with bevacizumab (plus chemotherapy) induces initial tumor stasis and shrinkage, followed by selection and emergence of more aggressive and resistant tumor clones, characterized by an accelerated growth, invasiveness and metastasis shifting the overall tumor growth kinetics to a steeper angle,” the researchers wrote in the abstract.
The researchers also noted that bevacizumab is effective for the time when it is administered to patients, which then follows a “slow rebound” after its discontinuation.
After 20 to 24 months, the initial survival benefit obtained with bevacizumab will be lost after its first administration, which was demonstrated in the FIRE-3, PARADIGM, PEAK, and CALGB 80405 studies.
Researchers reviewed the time-related effects of bevacizumab in trials assessing it in the first- and second-line settings to treat CRC, breast, ovary, and renal cancers. Through this, they found that there was a significant progression-free survival benefit obtained with bevacizumab, although this was not observed regarding overall survival. In addition, there was a detrimental effect on survival in the adjuvant setting in the AVANT and NSABP-08 studies, according to the abstract. Preclinical data on intratumor heterogeneity, clonal evolution, tumor biology, and the cross talk between bevacizumab and diverse tumor microenvironments was linked to the clinical data as a way to explain the time-related effects of the treatment, researchers wrote.
According to the background of the abstract, findings from the PARADIGM study of patients with CRC demonstrated a cross over of the bevacizumab survival curve below the survival curve for panitumumab (Vectibix) at the 28-month mark. This was followed by a steady decrease in the survival curve for bevacizumab below panitumumab’s survival curve by up to 11% by 5 years.
In other trials like FIRE-3, CALGB-80405, and PEAK, there were similar differences to what was observed in the PARADIGM trial starting at 20 months, “suggesting an unsuspected time-related effect of bevacizumab on patient’s survival starting at about 2 years after its first administration,” researchers wrote.
Reference
Aderka D, Muro K, Yoshino T. The crossover of the bevacizumab and panitumumab survival curves in the PARADIGM study: A clue to time-related effects of bevacizumab on the risk of tumor progression. J Clin Oncol. 2025;43(suppl 4):159. doi:10.1200/JCO.2025.43.4_suppl.159
