SCLC: Clinical Trials of Interest Using Novel Approaches



Mark A. Socinski, MD: Any optimism for any new agents in small cell lung cancer? We’re going to see some data on lurbinectedin.

Paul K. Paik, MD: The lurbinectedin data are pretty interesting. This is, for those who are not familiar, an agent that’s derived from the sea squirt. It takes about a ton of sea squirts to make a gram of trabectedin, which is a related compound. So clearly, to be environmentally friendly, we should be synthesizing this instead. But the lurbinectedin data are quite interesting in the second-line space. The response rate is quite nice—around 40%—with a median PFS [progression-free survival] of 4 months, which beats out a lot of what we see, certainly, with immunotherapy. There is a randomized phase III trial called ATLANTIS that’s going to combine this with doxorubicin—different ways of taking out action on DNA damage, basically. So I think there are still some compelling things that are out there, in addition to stuff that we haven’t mentioned in this space with PARP [poly ADP ribose polymerase] inhibition and things like that. So even outside of immunotherapy, there’s a lot of activity that I’m hopeful for.

Mark A. Socinski, MD: Others? Any thoughts?

Corey J. Langer, MD: We’ve seen our share of disappointments. Rovalpituzumab tesirine, affectionately called Rova-T, looked quite promising, at least initially. Ultimately, in phase II trials, in an expanded cohort, the response rate was less than 20%. The trial was marked by severe toxicity with major fluid retention. I think there are still some Rova-T trials out there. And I share your feelings that we’ve got to crack the nut here. We’ve got to really figure out some sort of immunotherapy combination approach that might have a benefit. But the absence of a benefit in the maintenance setting for the ipilimumab/nivolumab combination, which anecdotally I’ve given in relapsed patients, and we have actually seen some phenomenal survival.

I have trouble reconciling all of this, and I suspect that when we’re treating folks with extensive small cell disease in maintenance, we’re fooling ourselves. They’re not really maintenance. They’re probably having occult progression, and the drugs are just not working that well. We need to do a better job of figuring out which combinations to use, and certainly figure out that elusive biomarker that will enable us to choose the proper patients for these trials. And frankly, most of the advances are in atezolizumab with radiation, concurrent chemoradiation as opposed to sequential, and PCI [prophylactic cranial irradiation]. That’s spelled the survival differences over the prior 30 years.

Mark A. Socinski, MD: In extensive-stage disease, I think there are 2 controversial parities. Maybe one of them is not so controversial, and that’s the role of PCI. There was an initial enthusiasm for it after the EORTC trial, but then the Japanese trial kind of quelled that a little bit. And then, there is a remaining issue. Are there patients who have robust responses who may benefit from chest radiotherapy? Your thoughts?

Kristin Higgins, MD: Yes, and there was another European study that did show a 2-year survival benefit to thoracic radiation. Thoracic radiation was not delivered in IMpower133, so most of our patients are going to be getting carboplatin/etoposide/atezolizumab. Is thoracic radiation safe in that setting? It’s unknown. NRG Oncology is designing a trial right now for extensive-stage small cell disease that will incorporate thoracic radiation with immunotherapy. So there could be some continued advancements building on that backbone.

Mark A. Socinski, MD: Are people excited about the possibility, based on the survival benefit we saw in PACIFIC, that the ongoing trial in limited-stage small cell lung cancer will have a similar outcome?

Corey J. Langer, MD: Certainly, we hope so.

Heather A. Wakelee, MD: I think we have to be enthusiastic. We’re oncologists, Mark. We’re always optimistic.

Kristin Higgins, MD: NRG-LU005.

Mark A. Socinski, MD: Is that the name? OK. And the status of that trial is?

Kristin Higgins, MD: It activated on May 28, 2019.

Mark A. Socinski, MD: Oh, it just started.

Kristin Higgins, MD: It just activated. I think centers are starting to put it through. Hopefully we can start putting people on the trial.

Corey J. Langer, MD: Sadly, we’re still comparing 70 Gy to 45 Gy bid [twice a day], and that trial is just finishing.

Kristin Higgins, MD: Yes, that trial is ending and now LU005 is opening.

Ticiana A. Leal, MD: We are opening that trial, so we’re working on it too.

Kristin Higgins, MD: Yes.

Mark A. Socinski, MD: But to Corey’s point and to the credit of your field, all of the advances, certainly in limited-stage disease, have been at the hands of our radiation oncology colleagues. And so, that’s an integral part of treatment.

Kristin Higgins, MD: Absolutely.

Mark A. Socinski, MD: Is there anything you’re particularly excited about for limited-stage disease, from a radiation oncology point of view?

Kristin Higgins, MD: Well, our radiation technologies are always improving. Certainly, IMRT [intensity-modulated radiotherapy] techniques allow us to reduce radiation doses to the lungs and the heart. We know about image-guided radiation therapy in radiation planning. Those are all now standard of care and should be used when we’re giving curative doses of thoracic radiation. I think that proton radiation is being tested, and we have RTOG 1308 for non—small cell lung cancer patients. At ASCO [the American Society of Clinical Oncology meeting] this year, we saw an interesting abstract looking at proton versus photon radiation in locally advanced solid tumors, different histologies. There was actually a significant difference in acute high-grade toxicities. They were much lower with proton versus photon radiation, so that might be a home for that advanced technology going forward.

Transcript Edited for Clarity

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