Role of Newer Agents in the Treatment & Patient Selection

Vivek Subbiah, MD: In the clinic, if a patient walks in who has progression from frontline treatment and you have lurbinectedin available, would you use lurbinectedin over any other agent in the absence of a clinical trial?

Apar Ganti, MD: I would. As I said, the biggest adverse effect with topotecan has been myelosuppression and the ability to give it on a scheduled basis; you dose reduce to decrease the amount of myelosuppression. Based on what we know with lurbinectedin, I think that has a much better toxicity profile, and its myelosuppression seems to be lower than topotecan, so I would definitely use that.

Anne Chiang, MD, PhD: I agree. For these patients who have disease that’s not going to be cured, we’re looking for the ability to maintain their quality of life and use a number of different tools. This is something that’s well tolerated. It has a good response rate. The interesting thing will be for the patients who have platinum-resistance versus -sensitive disease. The 45% response rate for those patients who’ve had platinum-sensitive disease may point to this being an option prior to using platinum again. That’s something that remains to be seen, and it certainly depends on how the patients are doing. We need to get a little experience with this drug in the clinics.

Apar Ganti, MD: This is a very important point that you bring up about what you do in platinum-sensitive patients. We didn’t have any great options, so we used platinum again. Now we have another option that appears to be as good, this is something that we could potentially use. Having said that, I think there is still a role for rechallenging with platinum. We don’t have too many great options. If I have someone who has had 6, 7 months since their last dose of platinum and has a good performance status, I might challenge them with platinum/etoposide again because I know that I can use this drug later on when they relapse at some point, and the disease-free interval after the second platinum is less than with the first time they get it. With the sequencing of drugs, if they have a better performance status, they may be able to tolerate platinum/etoposide. If we give them lurbinectedin first and their performance status worsens when they progress, they may not be able to tolerate platinum/etoposide and will have to find some other drug at that time. That is a subtle nuance I might consider in treating those specific individuals.

Vivek Subbiah, MD: In the context of immunotherapy and lurbinectedin, when this lurbinectedin trial was designed, I don’t think immunotherapy was the standard of care. It was mainly available in clinical trials. Going through the clinical study, 2 patients (8%) had received prior immunotherapy as first line and 6 patients at second line as treatment. In a post-hoc exploratory analysis of this small group of patients, 5 of these 8 patients (63%) had agreeable responses to lurbinectedin, according to investigator assessment. Immunotherapy and lurbinectedin have different mechanisms of actions. When we combine immunotherapy patients who progressed from frontline immunotherapy or second-line immunotherapy, they could be candidates for lurbinectedin. We are waiting for further data on this, but having another drug in this area is a major boost in the clinic for patients.

Apar Ganti, MD: What you just said makes a lot of sense in the context of what we discussed earlier about responses to post-immunotherapy chemotherapy. As Dr Chiang said, evidence of great response to topotecan after someone had progressed on checkpoint inhibitors seems to be similar to what we found post-hoc in the lurbinectedin study. There may be some signal there about how previous immunotherapy may prime responses to subsequent cytotoxic chemotherapy. I think that would be a good topic for further investigation going forward since there are only a limited number of options for these patients, and we need to be trying to find creative ways of treating them.

Vivek Subbiah, MD: In summary, I think lurbinectedin appears to be a valuable treatment option and addition to our treatment armamentarium. The benefit of lurbinectedin compares favorably with that seen historically with topotecan and many of the new agents that have been recently tested in clinical trials in terms of both antitumor activity and safety.

Transcript Edited for Clarity

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