Potential Biomarker May Indicate Advantage with Tivozanib in Advanced Colorectal Cancer

A potential biomarker called NRP-1 (low serum neuropilin-1) may indicate longer progression-free survival (PFS) with tivozanib compared with Avastin (bevacizumab) as a first-line treatment for patients with metastatic colorectal cancer (mCRC), according to final results of the phase 2 BATON-CRC study.

“The increase in PFS for patients treated with tivozanib compared to bevacizumab is both interesting and encouraging,” principal investigator Al B. Benson III, associate director for clinical investigations at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said in a statement. “I believe that these findings warrant further study in a prospectively defined trial of patients with low serum NRP-1 metastatic colorectal cancer.”

Final results of the BATON-CRC trial, including results from a predefined biomarker analysis, were presented at the AACR Tumor Angiogenesis and Vascular Normalization Conference. The clinical trial randomized 265 patients in a 2 to 1 ratio to receive tivozanib, an oral tyrosine kinase inhibitor that acts against the tumor’s ability to signal blood growth to itself. The study tested tivozanib in combination with mFOLFOX6 or Avastin and mFOLFOX6. Patients were stratified by lactate dehydrogenase, origin of cancer and number of metastatic sites.

In the overall population, PFS and overall response rate (ORR) were comparable between both arms. PFS and ORR were 9.8 months and 46.9 percent, and 9.5 months and 43.2 percent for tivozanib and Avastin, respectively.

In the predefined biomarker analysis, patients with low NRP-1 showed an improved PFS compared with those with high NRP-1. Patients with serum NRP-1 levels below the median had longer PFS with tivozanib (17.9 months) compared with Avastin (11.2 months). This demonstrates NRP-1 may be a potential biomarker of tivozanib activity relative to Avastin, according to the researchers.

PFS was shorter in patients with high serum NRP-1 levels (7.3 months with tivozanib versus 7.5 months with Avastin).

“Where NRP-1 expression is low, the tumor appears to rely more heavily on the VEGF pathway and become more susceptible to anti-VEGF therapies, such as Avastin or tivozanib, an observation seen across several tumor types, including breast, gastric, colorectal and renal cell cancers,” said Benson. “Results from the BATON-CRC study are consistent with these observations.”

The overall safety profile was comparable in both arms. The most common adverse event was diarrhea. The most common severe side effect was neutropenia. Nine patients died while on treatment or within 30 days of last dose; 7 in the tivozanib arm and 2 from the Avastin arm.