Bevacizumab, in conjunction with 5-fluorouracil-based chemotherapy, is the standard first-line therapy for metastatic colorectal cancer (mCRC). In the second-line, improved survival has been demonstrated with continued antiangiogenic therapy using bevacizumab, aflibercept, and now, in the phase III RAISE trial, ramucirumab.

“The RAISE study population was chosen to be similar to the patient population encountered in clinical practice who are candidates for continued antiangiogenic therapy following progression on first-line antiangiogenic therapy,” explains Josep Tabernero, lead author of the study. Of note, the study enrolled patients who would have been excluded from previous phase III trials in this setting, including those with fast-growing tumours (first-line time to progression of <3 months), those with progressive disease >3 months after the last bevacizumab dose, and those who received bevacizumab for <3 months.

In the RAISE trial, ramucirumab added to second-line FOLFIRI was associated with a median progression-free survival of 5.7 months, versus 4.5 months for placebo plus FOLFIRI (P <0.0005). Importantly, median overall survival was also prolonged to 13.3 months with ramucirumab, versus 11.7 months with placebo (P = 0.0219).

“The trial results show that we now have another option to provide clinical benefit to patients in the second-line setting of mCRC,” states Tabernero. “We are proceeding with analyses to identify biomarkers that select for patients with tumours more sensitive to angiogenesis inhibition,” he continues. “Should such a predictive biomarker be identified, it may further improve the efficacy outcomes of trials assessing antiangiogenic treatments.”