Johanna C. Bendell, MD: You were the PI for the RAINBOW study, where we were talking about paclitaxel and ramucirumab. Tell us a little bit about what we’re seeing in that study.

Eric Van Cutsem, MD, PhD: The RAINBOW study was an important study, where patients in second line were pretreated with the doublet of fluoropyrimidine plus a platinum and were then randomized between paclitaxel plus or minus ramucirumab. The primary endpoint of the second-line study was survival, and there was a clear survival benefit of more than 2 months.

In parallel with that: the REGARD study led by Charlie Fuchs, which was a second line—best supportive care plus placebo versus best supportive care with ramucirumab. Also, this study, with survival as a primary endpoint, led to a positive outcome. Taking 2 studies together and looking also at the field of chemotherapy that’s cytotoxic—because previously we had seen that taxanes, as well as paclitaxel, docetaxel, or irinotecan in the second line in fit patients—could lead to a modest benefit, but there was some benefit if you select patients well.

If you look at the whole package together—chemotherapy and the study with ramucirumab alone, or the study with ramucirumab plus paclitaxel—you can clearly say that it’s OK to defend and that this goes in the guidelines. Ramucirumab plus paclitaxel is for fit patients and the standard option in the second-line treatment, because mean survival in this study was around 9 months for the combination.

If you look at just best supportive care, it’s treated 4 months, and with cytotoxic alone or with ramucirumab alone, it’s around 5 months. So, it’s gradually improved outcome, and this brings us to the concept to use more in colorectal cancer in the continuum of care; this strategic thinking of first line, a doublet eventually with trastuzumab; second line, paclitaxel and ramucirumab. Then in third line, if patients are still fit, irinotecan.

Johanna C. Bendell, MD: I think this is so interesting because, when we originally looked at antiangiogenic agents—the AVAGAST study—we thought that maybe they don’t work in the East; they mostly work in the West. But very interestingly, RAINBOW showed benefit of adding ramucirumab to paclitaxel everywhere, is that right?

Kohei Shitara, MD: Yes, we enrolled 104 patients from Japan, and it showed a very clear benefit in PFS and response rate. Overall survival result is hazard ratio of 0.88 in Japan and showed very long survival—nearly 1 year, but still keeps a trend. So, our guidelines accepted this result; also, Japanese regulatory authority is approving them soon, so this is the 1 standard treatment.

Transcript Edited for Clarity