Update on Small-Cell Lung Cancer - Episode 8
Transcript: Stephen Liu, MD: Anlotinib is an agent with some promise in the setting of previously treated small-cell lung cancer. This is a multitargeted tyrosine kinase inhibitor with activity at FGF, platelet-derived growth factor receptor, as well as vascular endothelial growth factor [VEGF]. Its efficacy was compared with placebo in a study of previously treated small-cell lung cancer and did show a progression-free survival benefit exceeding about 4 months compared with less than a month with placebo, certainly a promising signal of activity. However, in the third-line setting, will other agents have comparable efficacy? Will this be a drug that could be an option in the second-line setting?
Randomized trials with topotecan may be necessary to really show its clear efficacy in that setting. But certainly it is an agent with a lot of promise in pretreated patients. Interesting combinations with anlotinib may be developed in the near future.
Benjamin P. Levy, MD: Outside lurbinectedin, there are other drugs that are being tested. Certainly low-hanging fruit is other chemotherapies. And these are being tested. Many of the chemotherapies that are being tested are in phase II trials: gemcitabine, taxanes, nab-paclitaxel. There was a presentation, I believe, 2 years ago on nab-paclitaxel as a single agent in patients with extensive-stage small-cell lung cancer who had experienced disease progression. What we know is that the drug is reasonably well tolerated. I don’t think we know the outcomes of these agents, but they’re worth trying. Probably over time, we need to move away from chemotherapy or at least the old chemotherapy we have in extensive-stage small-cell lung cancer, given that responses are so transient in the second line, but these certainly are worth trying. And currently outside of being on a clinical trial, I do use a taxane or gemcitabine as second-line agents for patients with extensive-stage small-cell lung cancer.
Stephen Liu, MD: Nal-IRI [nanoliposomal irinotecan] is another drug with some promise in small-cell lung cancer. It showed a response rate of about 33% in the previously treated setting. This is higher than our current standards. But when we’re looking at previously treated small-cell lung cancer and drugs with activity, while we want to encourage their development, we have decades that have shown us response rates in this range. Really, larger numbers are necessary. While a response rate exceeding 30% is certainly promising, it’s a relatively small study. Larger trials, randomized trials are really needed to show clear efficacy of these agents. And we’ve learned over time to not put too much stock in early studies: to encourage their development but avoid early use of these drugs until we’re clear that they’re better than the currently available standards.
Benjamin P. Levy, MD: The ADRIATIC trial is mirroring the PACIFIC trial, which is evaluating the role of immunotherapy after concurrent chemoradiation in this setting for limited-stage small-cell lung cancer. We know from non—small-cell lung cancer that patients who have unresectable stage III non–small-cell lung cancer, who receive concurrent chemoradiation and at least have stable disease, garner benefit from consolidation durvalumab. And recently we’ve seen an overall survival advantage with that strategy.
This is somewhat similar, but this is in small-cell lung cancer. This is limited-stage small-cell lung cancer for patients who have received concurrent chemoradiation, then they’re randomized after receiving that—if they’ve achieved at least stable disease or have stable disease—to either durvalumab or durvalumab-tremelimumab, a dual checkpoint blockade strategy, versus placebo. And it’s trying to answer the question, can we improve outcomes and can we achieve, importantly, cure? Remember, we’re trying to cure limited-stage small-cell lung cancer, so this is trying to implement a strategy that can better lead to cure.
We don’t know the results of this yet. My hope is that consolidation immunotherapy either as a single agent or dual checkpoint blockade does improve outcomes. We have to remember that in limited-stage small-cell lung cancer, even though we’re going for cure, the median overall survival for this group of patients is anywhere from 18 to 22 months. We need to do better. The 5-year survival is only 10% to 15%. We need to do better, and this is a good way to start that conversation of how we can do better by delivering immunotherapy as consolidation and testing it out formally in a phase III trial.
Transcript Edited for Clarity