Comparing regorafenib plus chemotherapy to other biological drugs for the second-line treatment of metastatic colorectal cancer

This analysis was carried out to look at including regorafenib (Stivarga) in second-line therapy for patients with metastatic colorectal cancer (mCRC). The authors found that regorafenib in combination with chemotherapy might be an alternative to standard second-line treatment options for these patients.

Colorectal cancer (CRC) is currently the third most common cancer worldwide and is responsible for 10.2% of all new cancer diagnoses. mCRC that has spread around the body from its original location. Standard care for CRC that cannot be surgically removed is chemotherapy. mCRC is a difficult to treat disease with a poor prognosis. 

Regorafenib is a targeted therapy. It works by stopping cancer cells' growth and also stops the production of new blood vessels in tumors which often occurs in mCRC. This can help to slow the spread of cancer. Biological drugs like regorafenib are often added to chemotherapy in patients with mCRC. However, a comparison of different biological drugs has not been done. 

This analysis looked at 12 articles that involved 8 trials. Overall, 6805 patients with mCRC were included. Patients were treated with different biological drugs and chemotherapy or chemotherapy alone. The authors compared the safety and effectiveness of biological drugs such as bevacizumab (Avastin), panitumumab (Vectibix), ramucirumab (Cyramza), conatumumab (AMG-655), aflibercept (Eylea), and ganitumab (AMG-479) against regorafenib. 

Regorafenib was associated with an increase in survival without cancer worsening compared to aflibercept (by 4%), ganitumab (by 38%), panitumumab (by 4%), ramucirumab (by 9%). Bevacizumab, cetuximab, and conatumumab were associates with similar survival without cancer worsening compared to regorafenib.

Regorafenib plus chemotherapy resulted in similar overall survival when compared to aflibercept, bevacizumab, cetuximab, panitumumab, and ramucirumab. 

All drug combinations were considered more effective compared to chemotherapy alone in terms of response. Regorafenib was associated with a 20.3% increase in response compared to bevacizumab. There was no statistically significant difference between all the other drugs compared. 

Regorafenib was associated with a lower risk of severe side effects such as neutropenia (low white blood cells that fight off infections) and tiredness compared to cetuximab and conatumumab. Bevacizumab and cetuximab were associated with a lower risk of neutropenia with fever compared to regorafenib.

The authors concluded that regorafenib in combination with chemotherapy might be an alternative to standard treatment options in second-line treatment of patients with mCRC. 

This analysis included different studies and the comparisons were indirect. Further controlled studies are needed.