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Clinical Data With Lurbinectedin in Small Cell Lung Cancer
Key opinion leaders share a focused discussion on lurbinectedin and its evolving role in small cell lung cancer following frontline therapy.
Transcript:
Christian Grohé, MD: What do you think is the idea behind using a drug which obviously works in platinum resistant or platinum relapsed cancer, like lurbinectedin, and what’s your idea? Do you feel comfortable with using that drug? Is that a new thing we should use in most of our patients?
Laurent Greillier, MD, PhD: Yes. I think we should use this drug for the second-line setting. First, we can say that we have some data from the phase 2 trial where lurbinectedin was used in the second line for patients with small cell lung cancer after failure of platinum-based chemotherapy. The drug was given as a single agent. In the phase 2 trials, the dose was 3.2 mg/m2. It was given every 3 weeks until progression or unacceptable toxicity. The primary end point of this trial was the investigator assessed overall response rate, and the results were very impressive with the overall response rate around 35%. In the second-line setting for small cell lung cancer, it’s quite high. If we look in the different subgroups, if I remember correctly, the response rate in platinum-resistant patients, one is 22%. But the response rate in platinum-sensitive [patients] was very good, with 45% of response rate, which is quite the result for rechallenge with a platinum doublet. Globally, in my opinion, those results for lurbinectedin are very interesting. These are for patients [who are] platinum resistant or for platinum-sensitive patients. I heard that you have the drug available in Germany. In France, we have an early access program today, and we can use this drug for patients within the second-line setting or later-line setting.
Christian Grohé, MD: I think this is an important milestone and I think if this is going to be available generally in Europe, that’s going to be helpful. As you have pointed out, we have 2 different kinds of groups of patients. The group of patients who do not respond to platinum at all. We don’t really have anything for these patients left. Obviously, there are patients who have a better response for first-time treatment. Again, these patients should be in the condition that we can use that drug. In terms of what the standard of care is at the moment, topotecan or other older combination that you have already mentioned, I think this is definitely a step in the right direction. If you have a patient who is neither 180-day-free, platinum-free interval, the question is what to do with these patients. We have already mentioned that this is a very individual choice of the treatment option because all our patients tend to be older, frail, and elderly. So, a drug which is easily administered and easy to handle definitely would be helpful. It’s a 1-hour intravenous infusion every 3 weeks. That would be something in some of our patients, which would be more than welcome. If we think about the real-world evidence in general, we have a large second-line study already published, which clearly showed that there is a signal. What we do, again, have to understand [is] that, obviously, first-line therapy does play a role, of course, in second line, we have learned that the hard way in non–small cell lung cancer where we don’t really have new good data on second-line treatment option once I move to first line. We have to learn more about that for small cell, too. So, what do you think about the second-line setting, is that a question of toxicity? What makes you consider what kind of second-line recommendation you recommend to your patients and their families? What is the major idea behind the second-line treatment option?
Laurent Greillier, MD, PhD: I agree that the toxicity is a challenge for this patient, not the hematological toxicity, but on the other end it’s probably the toxicity. We are more comfortable to manage as an oncologist. I would say that all these chemotherapy drugs in the second line are mainly toxic for the hematological system. I think it’s not very difficult for us to manage all these drugs. I totally agree that we are dealing with patients with poor prognosis and the quality of life is very important. In my opinion, the less you stay at the hospital, the better it is. One-hour infusion every 3 weeks, it’s a very good advantage for lurbinectedin compared with the 3 days’ treatment with platinum-based and with platinum atezolizumab [or] 5 days for topotecan, for example.
Christian Grohé, MD: Yeah, absolutely. Toxicity-wise lurbinectedin, because it’s something which inhibits RNA polymerase, obviously does something to proliferating cells. The major problem we do see is mild suppression. In some of our patients that might be a problem, but compared to topotecan, which is something [where] we very often encounter a lot of thrombocytopenia or anemia, I think this is manageable, I think overall well accepted.
There is another second-line trial going on called LAGOON [NCT05153239]. LAGOON is a trial which will consider the standard of care in the respective countries, which would be a tecan, either topotecan, as we mentioned before, or irinotecan, which in only a few countries, mostly in East Asian countries, has been approved for the treatment of small cell lung cancer, but has the advantage that it’s only a 1-day business again, like it is for lurbinectedin, not 5 days or 3 days. That would be helpful. This is a trial which is currently enrolling and looks for patients who failed on standard of care, triple therapy, mostly. In addition to what we have is the beefing up of the maintenance therapy with new drugs like lurbinectedin or pump inhibitors. We have the option in patients who fail that we might have single drugs which might be helpful. This is a nice addition at the moment to the portfolio, which has been for a long period of time, not very fruitful in terms of what kind of new drugs would be helpful.
Transcript edited for clarity.
