Extensive Stage Small-Cell Lung Cancer - Episode 26

The Future of SCLC Management


Naiyer A. Rizvi, MD: I think you know we’ve covered a lot of different topics today. Maybe some final words if anyone wants to talk about what they’re excited about in the future for small cell lung cancer. And we can stop there.

Jamie E. Chaft, MD: I think Taofeek alluded to it earlier. There’s been a lot of work into really defining subsets of small cell. And we might finally be in a place, especially an extensive stage, where patients have that time to better biopsy and define their tumor while they’re undergoing what’s going to be standard of care with chemotherapy I/O [immuno-oncology], to really inform second-line therapies and later.

Naiyer A. Rizvi, MD: I think we still don’t understand a lot of the biology of small cell. We know that you know that they’re largely associated with RB [retinoblastoma protein] loss, which is a poor prognostic factor. Similar to other tumor types, they just perform really badly. But beyond that, we don’t know why they are PD-L1 [programmed death-ligand 1]—negative and have fewer immune cells. You know what else is going on with these tumors immunologically, even though they’re otherwise similar to non–small cell lung cancer care. There are efforts to do more analysis of tissue as our technology has improved to immune characterized tissues, and I think we’ll be able to gain a better understanding of what to do for these patients.

Ticiana Leal, MD: One of the things we’re interested in looking at is, can we re-explore the VEGF pathway in small cell in combination with immunotherapy—IMpower150 patient cohorts with small cell lung cancer, so to speak—with carbo [carboplatin]—ETOP [etoposide] and a combination with immunotherapy and a VEGF agent? I think really IMpower150 and CASPIAN have really set the stage and have shown that, yes, this combination is a combination that has activity and is well tolerated for patients, but how do we build on that regimen? And so thinking about additional strategies, I think the VEGF pathway may be bringing that back again and seeing if we can capitalize on that for small cell.

Taofeek K. Owonikoko, MD, PhD: Yeah, that’s actually great, in terms of what tests we can do for this patient. And surprisingly to me, the Chinese were able to test an anti-VEGF agent and got it approved as second-, third-line salvage treatment in China with erlotinib. And you know the response rates look reasonable. There was single-agent and antiangiogenic agent. And we know that people have attempted that also in the frontline setting in the combination with chemotherapy.

These studies were set for them to move forward, but there was always that trend. I think the 3 trials that looked at combination of angiogenic plus chemotherapy, you always saw the trending favor of the angiogenic, it wasn’t the other way around. So that’s probably something there to be said for that strategy.

The other thing is that some of the promising agents, this is based on phase II data, are now moving forward into phase III. So we have the anti-GD2 antibody toxin conjugate, the DISTINCT trial. That’s completed enrollment. It’s a phase III trial now comparing that standard of care agent in the relapsed setting.

And then we have the liposomal irinotecan, which was presented at the International Association for the Study of Lung Cancer World Conference on Lung Cancer 2019, where the response was about 44% in relapsed patients. Whether that would hold up in the randomized phase III trial, we don’t know yet, but that is also ongoing. Unlike where we were a decade ago, where this was a complete desert and nobody was interested, small cell is now becoming more interesting to both investigators as well as pharmaceutical sponsors. I’m hopeful that all these strategies will lead us forward and eventually result in new options of treatment of patients.

Naiyer A. Rizvi, MD: That was a great ending, thank you. Thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this OncLive® Peer Exchange discussion to be useful and informative.

Transcript Edited for Clarity