Patient Selection for Ramucirumab in NSCLC

Transcript:Enriqueta Felip, MD, PhD: I think the REVEL trial is a very interesting one. It is the study comparing, docetaxel/placebo and docetaxel/ramucirumab as second-line therapy in patients with nonsquamous or squamous histology. This trial showed that the combination of docetaxel and ramucirumab improved overall survival. And this is really important because patients with lung cancer need a number of treatment strategies. So, at present, we have, in second-line, the possibility to prescribe immunotherapy with an anti—PD-1 compound, or an anti-angiogenic compound plus docetaxel.

Marina Garassino, MD: When to use the combination of docetaxel plus ramucirumab, or nintedanib, or immunotherapy—I think that is the most relevant question for the treatment of advanced non–small cell lung cancer in second line. This is because the story of PD-L1 expression is still unclear. We don’t have a real cut-off, and we have trials in which it is clear that the benefit of immunotherapy is independent of the PD-L1 expression. However, I think that if we have a patient without a strong expression of PD-L1, it’s quite difficult to achieve a good response with immunotherapy. So, in patients with PD-L1–negative status or in patients with a low expression of PD-L1, I think that we have to think carefully about the possibility of using docetaxel together with anti-angiogenics. This is because if the patient’s disease progresses during second-line therapy with immunotherapy, it is possible that you are not able to treat the patient with docetaxel and anti-angiogenics anymore.

In my opinion, we have to think of a strategy of treatment for these patients. In patients with low expression of PD-L1, you have to try to use all the strategies, all the chemotherapies that you have available for these kinds of patients. So, in my clinical scenario, maybe I would use it before chemotherapy plus or minus anti-angiogenics in these kinds of patients.

Then, there are some data suggesting that anti-angiogenics work better in patients who have a bad outcome with the first-line chemotherapy and develop progression before 9 months. And there are subgroup analyses, but the advantage in these patients for combination chemotherapy is huge. And so, I think that we can also think of this possibility.

Roy S. Herbst, MD, PhD: Well, ramucirumab is approved in squamous and nonsquamous lung cancer alike. Nowadays, of course, it got approved just as immunotherapy for lung cancer. My suspicion is if someone is getting chemotherapy for lung cancer first line, their second-line choices would include immunotherapy or ramucirumab plus docetaxel, not used alone. My sense is many people might go to the immunotherapy first, though I would contend that perhaps you could look at a biomarker. If the patient is totally PD-L1—negative, you might want to go to the chemotherapy ramucirumab first, and the results are in combination with docetaxel. So, it will be used there in a setting where you would use docetaxel. If you’re not using chemotherapy as your second-line therapy in lung cancer and you use immunotherapy, then you’re saving your chemotherapy for the third line. Of course, many people like to use pemetrexed as their second-line therapy, so the issue is you’d have to use this drug with docetaxel. But, it’s a good drug, it’s a good combination, and it helps patients with a positive survival result, FDA approved.

Joachim G. Aerts, MD, PhD: The best candidates for anti-angiogenic treatment, in my view, we now have immunotherapy for second-line treatment, and to properly select patients is difficult, but we have to keep in mind that with the immunotherapy, we see impressive results. We see for the first time long-term survival, so that’s really, really impressive. But, on the other hand, we have to take into account that that’s the minority of patients. So, the majority of patients we lose before that. And, certainly, for immunotherapy, we know that when you look at the trials, you lose about 30% of patients already in the screening period. These are the patients who are having the rapid progression—and, even shortly after chemotherapy, or even during chemotherapy. And, I think, these are the patients in whom we probably better start with the chemotherapy in combination with the anti-angiogenic agent at this point of time.

And we don’t know what’s coming up—but for now, we know that looking at the first month after the start, also in the immunotherapy trial comparing it to docetaxel, we saw that we lose more patients on immunotherapy than on the docetaxel.

So, I think we have to do a proper patient selection, and for now, we know that rapid-progressive patients are certainly one of these patients whom we should treat. The other thing is how to introduce this PD-L1 staining and select patients based on that. And, also, to that point, my personal opinion is that PD-L1—negative patients should be treated with other agents and immunotherapy at this point, based on the scientific knowledge we have now.

Transcript Edited for Clarity