Charles S. Fuchs, MD, discusses the impact of the approval of ramucirumab in metastatic colorectal cancer and what further research is needed for the optimal utilization of the VEGFR-2 inhibitor.
Charles S. Fuchs, MD, MPH
After receiving approvals for advanced gastric cancer and metastatic non—small cell lung cancer in 2014, ramucirumab (Cyramza) was approved by the FDA in April of this year for use in combination with FOLFIRI as a second-line treatment for patients with metastatic colorectal cancer (mCRC).
The VEGFR-2 inhibitor showed promising results in the phase III RAISE trial that led to its approval, extending overall survival by 1.6 months and progression-free survival by 2.2 months compared with FOLFIRI alone in patients with mCRC.
The FDA approval for ramucirumab in mCRC came quickly; the drug was reviewed and approved within just 9 weeks, according to the manufacturer of the drug, Lilly Oncology. This is significantly faster than prior applications, for which the approval process took 6 months.
OncLive spoke with Charles S. Fuchs, MD, director of the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, to get a better understanding of the impact of the approval of ramucirumab in mCRC and what further research is needed for the optimal utilization of the drug.Dr Fuchs: I think that the study really demonstrates that VEGF/VEGFR inhibitors are an important component for the treatment of colorectal cancer. It does seem to work well with established chemotherapy and it is well tolerated. Having another treatment available for these patients is very valuable.One challenge in targeting this particular VEGF pathway is trying to understand if there are biomarkers that inform which patients achieve the greatest benefit with these inhibitors. That has been a challenge. Right now the drug does benefit every patient; however, it is not clear if there is a patient that benefits more or less.
Others and myself are trying to do work to understand if we can derive, through studying blood or tumor or both, a marker that actually defines which patients would have the greatest benefit. At this point we do not know which subset defines the greatest benefit either defined clinically, pathologically, or molecularly. But I do think that is an opportunity that we want to pursue.
This is an important area of investigation for all targeted therapies, but for VEGF specifically it very important. Even though we’ve known about this pathway for a long time and we’ve had drugs under development for a decade or longer, we haven’t been able to identify an informative biomarker. Newer technologies are now available and I hope that we can sort this out.There is reason to believe that this drug might work equally well with a variety of systemic chemotherapies beyond FOLFIRI. Studies investigating this have not been sufficiently completed so the end results remain to be seen. My guess is that there is a benefit of ramucirumab when adding to alternative chemotherapy regimens, but that needs to be proven ultimately. There is also the possibility that it could benefit patients by itself in more refractory settings. That is another area worth considering that has not been studied.
We should also consider the possibility of adding it to other biologics. That is a really interesting opportunity for future investigation. There is evidence that other pathways intersect or potentially compliment VEGF pathways. So if you jointly inhibit them, you might get some measure of synergy. This is all hypothetical, but I think what we want to do is start to test ramucirumab with other targeted therapies that are under development and see if we can see some synergy based on biology.The RAISE study had a relatively clean result. There were not a lot of issues. What we have seen in circumstances like this when the study is soundly conducted and there really aren’t any specific issues is they’ve ultimately approved these drugs very quickly.There are probably other diseases where VEGF inhibition might be beneficial. Angiogenesis is an item that is not specific to one particular malignancy. It is a phenomenon that is fairly ubiquitous in cancer development and progression.