Naiyer Rizvi, MD: So for patients that get chemo [chemotherapy], they’re on maintenance atezo [atezolizumab] and they progress—Josh, what do you do? Do you give them ipi/nivo [ipilimumab/nivolumab]?

Joshua Bauml, MD: Not if they’re progressing on atezolizumab. I don’t do that. I hope for a clinical trial. Our options are really bad right now. I think that we’re left with topotecan as the standard of care, which I don’t think any of us really like using. We’ll sometimes use irinotecan. I’ll use a taxane, but the truth is we don’t have a good option after progression on chemotherapy for extensive stage small-cell lung cancer. If somebody has had progression after 6 months off chemotherapy, I would do platinum re-exposure with platinum etoposide or platinum irinotecan depending on various features, but we don’t have good options there. It’s a space where we really need good research. There are some drugs that are emerging, such as lurbinectedin but that is where we are.

Naiyer Rizvi, MD: Jacob, there was nice data from your group around temozolomide and PARP inhibitor combinations. Is that something that you use, or what do you think?

Jacob Sands, MD: Well, to be clear, that is Anna Farago out of MGH [Massachusetts General Hospital] who is leading that, and I’ll say some patients tend to do really well on this, and it’s generally very well tolerated. Cytopenias can be an issue. Occasionally, fatigue can be an issue. That’s really something for clinical trial, but we’ll see where that data pans out ultimately. It’s been promising. I know that was presented in an ASCO [American Society of Clinical Oncology] poster a couple of years ago: 40% response rate and generally well tolerated. In this scenario, that is very compelling. So hopefully that pans out further.

Naiyer Rizvi, MD: And, Leora, lurbinectedin is supposed to be reviewed by the FDA at some point this year. Do you have any experience with that?

Leora Horn, MD, MSc: I don’t. I’ve been watching the data, and it’s interesting. I think we need to wait for the phase III because we see a lot of positive phase II data, and then the phase III trials come out, and they’re not quite as exciting. You know, the phase III also incorporated Adriamycin [doxorubicin] into therapy, which is another drug that I like to use in this group of patients because of their cardiotoxic disease, but it would be nice to have a new second-line option. Paclitaxel has always been my go-to regimen.

Jacob Sands, MD: So I do have some experience, and I think this is a drug that’s generally been very well tolerated, and again we’re seeing response rates that are in the compelling range, initially around 40%. The more recent data is more in the 30s, but response rates that are compelling in a generally well-tolerated drug. It is interesting, I agree, that Adriamycin is not a drug I’m excited to use, but to say that the adverse effect profile has been good enough that you can pair it with Adriamycin. Interestingly, that trial is randomized to topotecan versus CAV [cyclophosphamide/adriamycin/vincristine], or you can choose either topotecan or CAV in a patient who gets randomized to the control arm. In the very beginning of that trial, oncologists were utilizing topotecan, and then I guess remembered why they don’t like topotecan, and then we saw an increase in people using CAV as the control arm in that group, which just makes the point that we don’t have a very good next line approved option. For a drug that is well tolerated to have response rates in the 30s or even up to 40% is very compelling. I do think the data on this is fairly impressive, although I agree there is not yet a lot of it. So we’ll see what happens.

Leora Horn, MD, MSc: It will also be important to remember that the phase III data, when it does come out, is in the patients who got chemotherapy. That was prior to the patients getting chemotherapy/checkpoint inhibitor combinations.

Jacob Sands, MD: That’s right. You know, the other thing I’ll say though for lurbinectedin, in the single-arm lurbinectedin it really showed some nice responses even in those who had early progression of disease. And after platinum etoposide. That has been a really resistant population that’s very hard to treat. Now, those who had longer durations of response more than 6 months out of control after platinum/etoposide, getting lurbinectedin did better than those with the early resistance to platinum/etoposide getting lurbinectedin, but in both groups we see responses to therapy. So it is a compelling option, and we’ll see as the data comes out.

Naiyer Rizvi, MD: Thanks to everyone for really an excellent, lively, informative discussion. Before we conclude, I’d like to get final thoughts from each of you. It can be what you’re excited about that’s going to be coming up in the near future, or anything you want to sort of chat about as a final thought. Josh?

Joshua Bauml, MD: I think this is a very exciting time to be doing research in lung cancer. There have been so many wonderful advances, which we have been able to talk about today, but there’s so much more work to be done, both in the immunotherapy space, where I think we really need to identify a biomarker, and in the targeted therapy space where we need to manage resistance. So I think there is a lot of work still to be done.

Naiyer Rizvi, MD: Leora?

Leora Horn, MD, MSc: It’s an exciting time to be in lung cancer with old and new agents that are approved. I think what I’m looking forward to seeing in the next few years is what’s going to happen in early stage disease. I feel like we’ve made a lot of progress in late stage disease, but the majority of our patients with early stage disease still recur, and so will checkpoint inhibitors or targeted therapies in the adjuvant or neoadjuvant setting increase our chance of curing more of our early stage patients?

Naiyer Rizvi, MD: Tim?

Tim Kruser, MD: I think a lot of kudos is deserved by the medical oncology community for making me a sideline player for a lot of places where I used to have to give whole brain radiation for people we now know don’t need that for molecular driven tumors. That said, it’s also a great time to be a radiation oncologist in the lung cancer setting and give immune priming radiation to help improve the response for systemic treatment. So keep your local radiation oncologist in mind as a partner.

Naiyer Rizvi, MD: And Jacob?

Jacob Sands, MD: This is an exciting time for lung cancer treatment. It’s only been about 10 years since initially in the clinics treating people with EGFR TKI [epidermal growth factor receptor tyrosine kinase inhibitor] for the first targeted therapy. Since then we now have an array of targets, an array of drugs, some in multiple cases have multiple drugs for a single target. So there’s a lot that’s gone on with immunotherapy that is benefitting our patients also. There’s a lot happening.

One thing, going to what Leora Horn said about early stage disease in a topic not really covered within this talk and a big topic in itself, is lung screening. With lung screening, we are really able to detect cancers much more commonly at an earlier stage, at which point this is more curable, and I think the potential benefits of lung screening really may outweigh any one of these things that we’ve talked about once it’s more widely done.

Naiyer Rizvi, MD: Okay. Thank you all very much, and to our viewing audience as well. We hope you found this OncLive® Peer Exchange discussion to be useful and informative. Thank you.

Transcript Edited for Clarity