A recent analysis of biomarkers from a phase II clinical trial has identified several potential predictors of response to the combination of camrelizumab (anti-PD-1) and apatinib (anti-angiogenic) in patients with advanced triple-negative breast cancer (TNBC).
The original trial demonstrated that this combination therapy induced an objective response rate (ORR) of 43.3% in advanced TNBC patients. This follow-up biomarker study aimed to identify factors that could predict which patients would benefit most from this treatment approach.
Tumor Microenvironment Biomarkers Show Strong Correlation with Outcomes
Researchers analyzed tumor samples from 28 patients using immunohistochemistry to evaluate tumor-infiltrating lymphocytes (TILs), CD8+ T cells, and PD-1/PD-L1 expression. The results showed that baseline TILs were significantly associated with longer progression-free survival (PFS) (P = 0.035).
Additionally, patients who experienced an increase of tumor-infiltrating CD8+ T cells of at least 15% during therapy demonstrated a higher objective response rate (P = 0.040). These findings suggest that the pre-existing immune microenvironment and its dynamic changes during treatment play crucial roles in determining therapeutic efficacy.
Plasma Biomarkers Predict Treatment Response
The study also examined 59 cytokines, chemokines, growth factors, and checkpoint-related proteins in blood samples using multiplexed bead immunoassays. Several key findings emerged:
- Patients with lower baseline plasma levels of hepatocyte growth factor (HGF) or interleukin-8 (IL-8) were more likely to respond to treatment (P = 0.005 and P = 0.001, respectively)
- Lower baseline HGF and IL-8 were also associated with longer PFS and overall survival (OS)
- Patients who showed a decrease in IL-8 levels during treatment responded better to therapy (P = 0.008)
- Increases in T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) or CD152 during treatment correlated with better response (P = 0.040 and P = 0.014, respectively)
Blood Immune Cell Profiles Differentiate Responders from Non-Responders
Flow cytometry analysis of blood immune cell subpopulations revealed that responders had significantly higher baseline proportions of CD4+ T cells and B cells compared to non-responders (P = 0.002 and P = 0.030, respectively). This suggests that the systemic immune status before treatment initiation may influence the therapeutic outcome.
Implications for Personalized Treatment Approaches
These findings have important implications for the clinical application of combined anti-angiogenesis and immunotherapy in TNBC. Dr. Liu, one of the study authors, noted, "These biomarkers could potentially help us identify which TNBC patients are most likely to benefit from the camrelizumab plus apatinib combination, allowing for more personalized treatment decisions."
The identification of these biomarkers may enable clinicians to select patients who would derive the greatest benefit from this combination therapy, while sparing others from unnecessary treatment and potential adverse effects.
Study Limitations and Future Directions
The researchers acknowledge that the sample size of 28 patients is relatively small, and larger validation studies will be needed to confirm these findings. Additionally, the complex interplay between anti-angiogenic effects and immune modulation requires further investigation.
Future studies will likely focus on developing composite biomarker signatures that integrate multiple parameters to more accurately predict treatment outcomes. There is also interest in exploring whether these biomarkers are specific to the camrelizumab-apatinib combination or could apply more broadly to other immunotherapy-antiangiogenic combinations in TNBC or other cancer types.
As triple-negative breast cancer remains one of the most challenging breast cancer subtypes to treat, with limited targeted therapy options, these biomarker findings represent an important step toward optimizing treatment selection and improving outcomes for patients with this aggressive disease.
