A panel of expert oncologists offer closing thoughts on the future treatment landscape and unmet needs in small-cell lung cancer.
Taofeek K. Owonikoko, MD, PhD: In the last couple of minutes, Dr Leventakos, can you talk to us about some of the promising clinical trials in this setting?
Konstantinos Leventakos, MD, PhD: The second line is quite challenging because usually the patients progress, and you have to find the time to put them into a clinical trial quite quickly. So, I know how difficult some of these trials are. There are 2 different approaches that I have seen. One is based on the idea that lurbinectedin has some preclinical data that it may have some immunomodulatory effect, so let’s combine it with immunotherapy. This is where we see the LUPER study coming from Spain, which is looking into the combination of lurbinectedin with pembrolizumab. Interestingly, this is a population that does not have experience with immunotherapy at first. I don’t know how that might change in our time when everybody is getting immunotherapy in the first line.
At the Mayo Clinic, we have a clinical trial that is looking for patients who progress on chemotherapy immunotherapy, and we continue immunotherapy by means of durvalumab and we add lurbinectedin. We do not have any results from our trial, but I know that the LUPER team has seen some promising results in the phase 1 study. Interestingly, they did the dose escalation to go to the final dose, which is 3.2 mg/m2. They didn’t have safety events, and in our safety lead-in, we didn’t have any safety events. I think we can say that we could combine that.
The other approach is to look into other well-known molecular mechanisms in small cell [lung cancer]. Other studies are looking at lurbinectedin with an ATR inhibitor, and we are looking eagerly into these results. But I think these are the main avenues I see, immunotherapy with lurbinectedin, or targeted agents with lurbinectedin at this point.
Taofeek K. Owonikoko, MD, PhD: Thank you. Dr Sands, [what are] your thoughts in terms of unmet needs in this area, especially in the second line and beyond?
Jacob Sands, MD: I’d say it’s plentiful in the second line and beyond. I want to highlight 2 things though. Before I say that, the comment Dr Leventakos made earlier about there being second-line options is such an important one. There are also third-line options, and if needed, there are fourth-line options. Now these aren’t the most appealing, and this is why we all say clinical trials. But I do find it tragic that there are patients with good functional status who want a next line who are being offered hospice as their next line of therapy. And I do sometimes see patients come in thinking, “I know there’s not anything, but I just had to hear it from you.” And they come in, and I say, “No, there are treatment options.” We then start something. Now, none of these options in the second line and beyond that we’re talking about work well enough. So, we absolutely need other studies, and this is where enrollment in trials is so important. But I just want to stress to everyone out there that there are options, and we should make sure that everyone is getting offered a reasonable option if they have a good functional status and it’s an option for them.
But then next, despite the need, I am also very optimistic about the array of trial drugs that are out there. I think right now we’re in this exciting time where there are more drugs being developed in small cell lung cancer in trials than I think the culmination of all the prior drugs before. I see us on the cusp of a new era, where we have other groups of patients where we see home run results with them. And it’s always going to be an effort of how do we do more? We’ve had a handful of drugs we’ve discussed that were a step forward, and now we have drugs that I think are on the cusp of being a huge advance for a subset of patients. It’s then going to be the next level of how we move through biomarkers and identifying patients, as Dr Chiang highlighted earlier, as well as even more novel drug development beyond that.
Taofeek K. Owonikoko, MD, PhD: That’s very insightful. On that note, I really want to thank you all for this very rich and informative session. But before we conclude, I want to give you each the option of sharing your clinical pearls and perspectives on the future of small cell lung cancer with our community colleagues treating patients with these very challenging conditions.Dr Chiang, can you provide us with some closing thoughts?
Anne Chiang, MD, PhD: I agree with Dr Sands, this is a really exciting time for small cell. I think we’re developing this idea that we can have precision medicine, that there’s not just 1 uniform small cell lung cancer, there are subtypes that we can leverage. And we hope to be able to understand why some of the trials in the past were negative. Maybe we didn’t capture the right population. There was another drug at ASCO [the American Society of Clinical Oncology annual meeting], a bispecific drug, that was very exciting. And I know that Amgen has another exciting bispecific drug that, again, because we don’t have PD-L1, we don’t have so many tumor lymphocytes in the tumor, maybe we need to draw them over there, either by the bispecific or maybe through an antibody-drug conjugate. I think that’s another exciting approach.
But overall, my message is that I think we’re going to make progress by this time next year, and that we are starting to develop some real inroads into helping our patients with small cell.
Transcript edited for clarity.