Benjamin A. Weinberg, MD, FACP
Emerging data have helped to elucidate the real world experience of regorafenib vs trifluridine/tipiracil in the third-line setting. In a single-institution retrospective study, Patel and colleagues evaluated 126 patients who received trifluridine/tipiracil and 95 patients who received regorafenib. There were higher response and disease control rates seen with trifluridine/tipiracil, although median overall survival was similar (7.5 vs 7.1 months). These findings are limited by the single-institution, retrospective and non-randomized nature of the study. Also, the better-tolerated ReDOS dose-escalation schema for regorafenib was not utilized in this study, and it would be interesting to see how this novel dosing strategy compares to trifluridine/tipiracil in the real world setting.
Immunotherapy with anti-programmed death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) monoclonal antibodies has proven to be very effective in the rare group of patients with mCRC harboring deficiencies in mismatch repair, but has unfortunately largely fallen short for the vast majority of patients with mismatch repair proficient cancers. Martinelli et al. looked at adding avelumab, and anti-PD-L1 antibody, to cetuximab in an effort to rechallenge patients with RAS wild-type disease to anti-EGFR therapy in the single-arm phase 2 CAVE trial. 77 patients were treated and the median overall survival was an impressive 11.6 months, increasing to 17.3 months in patients with circulating tumor DNA (ctDNA) that was wild-type for both RAS and BRAF. This study suggests that rechallenging with anti-EGFR therapy can be effective in a ctDNA-selected population and that immunotherapy may have a role to play in this setting, although these findings would need to be confirmed in a larger, randomized phase 3 trial.
Finally, the COVID-19 pandemic has upended medical care, including oncology care. Thierry and co-workers evaluated the effect on the pandemic lockdown in France by looking at the baseline levels of ctDNA in 80 patients with newly diagnosed mCRC presenting pre-lockdown vs. post-lockdown. They showed that median ctDNA was much higher post-lockdown (119.2 vs 17.3 ng/mL), implying that delays in diagnosis related to the pandemic led to more advanced mCRC, at least in terms of ctDNA level. This study adds to the growing literature demonstrating that COVID-19 will continue to have effects on cancer care and cancer-related mortality for years to come.