Recent Advances in Small-Cell Lung Cancer - Episode 9

Q & A and Final Thoughts

August 20, 2020
Vivek Subbiah, MD, MD Anderson Cancer Center

,
Anne Chiang, MD, PhD, Yale School of Medicine Smilow Cancer Hospital

,
Apar Ganti, MD, University of Nebraska Medical Center

Vivek Subbiah, MD: Before we end this discussion, we’d like to incorporate some of the questions submitted in advance by our viewing audience. I think we’ve touched upon several of these during the course of our discussion, but let’s take one at a time.

Is there a role for NGS [next-generation sequencing] testing in small cell lung cancer, given that NTRK, TMB [tumor mutational burden], and MSI [microsatellite instability] have a histology-agnostic approval for agents and more physicians are going to be testing for a broad-based panel? Is there a role for NGS testing in small cell lung cancer? Dr Chiang?

Anne Chiang, MD, PhD: I would love to do NGS testing on all of these patients, but it’s not covered, at least not upfront. I do think, upon progression, it is something that I try to do with these patients. I try to get information, a biopsy if it is appropriate, often on a clinical trial, to try to understand more if there are other therapeutic options for these patients. Many of them, as you mentioned at the beginning, will have RB or TP53 mutations that we don’t have a target for, but if there are other targetable mutations, that’s part of creating more tools to combat the disease for individual patients.

Vivek Subbiah, MD: Dr Ganti, we spoke about lurbinectedin. This seems like a new drug that will be an added value to our treatment. What would potential combination therapies with lurbinectedin look like? Do you think it can be combined with other agents?

Apar Ganti, MD: I think so. If you look at the mechanism of action of lurbinectedin and the safety profile, it is fairly safe. You could potentially combine it with either other cytotoxics or with immunotherapy because we know that, at least in the non–small cell lung cancer setting, chemotherapy plus immunotherapy seems to have a better response rate than immunotherapy alone. That is an approach that we could borrow from that disease paradigm to use in the relapsed setting. If you could understand the mechanisms of resistance for lurbinectedin, we could potentially combine it with drugs that would work on providing disease control and progression-free survival. Those are definitely options that I would consider right now. As we understand more about the biology of small cell lung cancer, I’m hoping we’ll find new pathways and try to identify ones where they would be synergistic with lurbinectedin and use that in combination. There is potential for combining it because it seems to be a relatively well-tolerated drug.

Vivek Subbiah, MD: Dr Ganti, Dr Chiang, thank you. Small cell lung cancer remains a challenging disease in need of new therapeutic opportunities. Lurbinectedin appears to be a new, valuable treatment option. Activity of lurbinectedin in combination with doxorubicin for second-line in small cell lung cancer therapy is being investigated in a randomized phase 3 trial, ATLANTIS. We also saw that the use of immunotherapy can benefit patients with small cell lung cancer by generating effective antitumor responses in the host. Considering this disease is an immunogenic tumor with highly somatic mutation breaks, it also displays a very immunosuppressive phenotype that hinders the therapeutic advances in immunotherapy. This may biologically explain, in part, the recent conflicting results of the efficacy of various immune checkpoint inhibitors in small cell lung cancer. The results of ongoing large, randomized studies, including the one for lurbinectedin with doxorubicin—along with future research and novel immunotherapeutics, as well as newer combinations—are expected to define the final role of immunotherapy and all other agents in the treatment algorithm for small cell lung cancer.

This has been an excellent discussion, and thank you for your participation. To our viewing audience, we hope that you found this information to be valuable to your clinical practice. Thank you all for watching this OncLive News Network® broadcast.

Transcript Edited for Clarity