Dr. Grothey on Combination Therapies with Regorafenib and TAS-102 in CRC

Axel Grothey, MD, a medical oncologist and director of Gastrointestinal Cancer Research at West Cancer Center and Research Institute, discusses combination therapies with regorafenib (Stivarga) and trifluridine/tipiracil (TAS-102; Lonsurf) in colorectal cancer (CRC).

Last year, a dataset of the phase 1b REGONIVO study, a Japanese study, was presented; this trial evaluated regorafenib at a low dose of 80 mg plus nivolumab (Opdivo) in patients with CRC and gastric cancer, says Grothey. Some of the patients with gastric cancer had been pretreated with nivolumab and experienced disease progression. There were remarkable response rates in both cohorts, though the benefit has not yet been replicated in a Western population. The Japanese population had many patients with rectal cancer and lung metastases, which is believed to have a different immune environment that might respond better to augmented immunotherapy, Grothey explains.

This idea of combining a multikinase inhibitor plus a PD-1 antibody is intriguing, because additional data have been noted in other cancers with lenvatinib (Lenvima), which is a similar agent when compared with regorafenib. It has been used in combination with pembrolizumab (Keytruda) in endometrial cancer. The idea of a multikinase inhibitor plus a PD-1 antibody is attractive, explains Grothey.

Another combination is TAS-102 with bevacizumab (Avastin). The active component of TAS-102 is trifluridine, which is a fluoropyrimidine—a compound that bevacizumab works well with. Data from a later-line randomized Danish trial with TAS-102 with or without bevacizumab revealed that 93 patients showed a significant improvement in progression-free survival and overall survival with good tolerability, says Grothey.

Additionally, a recent 2020 publication in Annals of Oncology spotlighted a European study, ] comparing capecitabine (Xeloda) plus bevacizumab with TAS-102 plus bevacizumab. This was a randomized trial that was performed in patients who were not candidates for oxaliplatin or liposomal irinotecan (Onivyde). Those patients experienced a numeric difference in benefit from TAS-102 over capecitabine when bevacizumab was added. There are also later-line data and early-line data supporting the combination, though bevacizumab should be used in combination with TAS-102 in patients with CRC, concludes Grothey.