An Important Advance in 3rd-Line Treatment for Refractory Colorectal Cancer

An important advance has occurred in the treatment of stage 4 colorectal (large bowel) cancer. A clinical trial called SUNLIGHT showed that, in refractory metastatic (stage 4) colorectal cancer, adding bevacizumab to trifluridine/tipiracil improved survival as a new standard of treatment.

According to the results, adding bevacizumab increased median survival compared with patients receiving only trifluridine/tipiracil (Lonsurf) to 10.8 months, versus 7.5 months with Lonsurf alone, and reduced the risk of death by 49% (hazard ratio, 0.61; P < 0.001). The addition of bevacizumab also did not increase the risk of serious adverse effects or events leading to treatment discontinuation. Oncology specialists regard these findings as a development that will change the treatment approach to colorectal cancer.

This notable study was presented on 21 January at the 2023 Gastrointestinal Cancers Symposium (2023 ASCO GICS).

The study included patients with stage 4 colorectal cancer whose disease had progressed after 2 lines of systemic treatment.

Until this study, standard 3rd-line treatment for metastatic colorectal cancer consisted of single agents, either Lonsurf or Stivarga (regorafenib). We did not know the outcome of adding another agent, such as bevacizumab, in a comprehensive phase-III clinical trial.

Bevacizumab is a well-known anticancer agent that targets vascular endothelial growth factor (VEGF) and suppresses angiogenesis (the formation of new blood vessels).

SUNLIGHT enrolled 492 patients, randomly assigned to two arms. In both arms, most patients (72%) had previously received bevacizumab.

Table 1. Summary of Baseline Participant Characteristics

At 6 months, overall survival was 77% with combination treatment versus 61% with control treatment; at 12 months, it was 43% versus 30%.

Median progression-free survival was 5.6 months in the combination arm versus 2.4 months in the control arm (HR, 0.44; P < 0.001). Progression-free survival at 6 months was 43% versus 16%, respectively, and at 12 months 16% versus 1%.

Table 2. Summary of Overall and Progression-Free Survival

No treatment-related deaths were reported, and serious adverse-effect rates were similar in the two groups. Overall, adverse effects were similar in both groups except for slightly higher rates of hypertension (10% versus 2%), nausea (37% versus 27%) and neutropenia (62% versus 51%) in the bevacizumab plus Lonsurf arm.