Recent Advances in Small-Cell Lung Cancer

Video

Suresh Ramalingam, MD:Let’s talk about the recent advances in small-cell lung cancer. For almost 3 or 4 decades, we used chemotherapy as the frontline treatment for this disease, platinum-etoposide being the platform regimen. Now we have a new standard of care in the form of chemotherapy plus immune checkpoint inhibition. We have 2 approved drugs in this setting, atezolizumab and durvalumab, in combination with chemotherapy. Firas, let me get your thoughts on, briefly, the high points of the data and some of the recent updates we heard at ESMO 2020 [European Society for Medical Oncology Congress].

Firas Badin, MD: As you mentioned, it’s been a long time since we had any breakthroughs in small-cell lung cancer, despite the wide adoption of immunotherapy as well as target treatments in non–small cell lung cancer. It seemed as if we were stuck with small-cell lung cancer platinum doublet first line followed by topotecan second line, until these 2 nice randomized studies, the IMpower133 as well as the CASPIAN trial. Fairly similar design, very similar patient population, first-line small-cell lung cancer, extensive stage, treatment-naïve, randomized to receive either standard chemotherapy, platinum-etoposide, vs the same chemotherapy with atezolizumab in IMpower133 or durvalumab with or without tremelimumab in the CASPIAN trial. Both studies showed an overall survival advantage with the addition of PD-1 or PD-L1 inhibitors in first-line small-cell lung cancer.

With the updates from ESMO, they tried to look at those patients who had done very well, who had extended long-term survival, and see why did these patients have or who are those patients who had extended long-term survival. Both trials also had similar findings. I’m not surprised that of patients who did receive immune checkpoint inhibitors, the group who had the triplets had more patients who achieved longer term of survival, as well as patients who had fewer brain metastases, fewer liver metastases, and excellent performance status, as well as women. There were more patients in those categories who had more extended long-term survival.

There are still a lot of things that we need to learn from small-cell lung cancer. I don’t think we have appropriate biomarkers for treatment in this difficult disease, but it’s good to have options today for our clinic for those patients with this bad disease.

Suresh Ramalingam, MD: Certainly. Steve, you were one of the PIs [primary investigators] of the Impower133 trial that studied atezolizumab in combination with chemotherapy. How have these trials changed your practice?

Stephen Liu, MD: It’s our new standard of care. I appreciate that the hazard ratio is not 0.1, but I know that the 5-year survival is not 90%. I know it’s not as good as we had wanted. There’s no question in my mind that it’s clearly better than what we had and deserves to be our new standard. What we’re learning as more data come out is that we have no way to identify who those patients are. Whether it’s TMB [tumor mutational burden], PD-L1, we simply don’t have utility in patient selection, and right now it is an all-comer approach. I get that that’s frustrating when we know the benefit is carried by a subset. Today the only way to make sure that subset gets the treatment is to offer everyone the opportunity to get immunotherapy. But we need to build on that, whether it’s newer, more novel, more expansive combinations on that backbone or finding treatment using subtypes, for example. A lot of the work at your own institution is done on different transcriptional subsets of small cell.

Suresh Ramalingam, MD: Christine, we all have the first drug approved with atezolizumab and chemotherapy, and we started using it. Then came the CASPIAN results. Talk a little about potential differences you see between these 2 trials. How do you adopt the CASPIAN results and the durvalumab approval in your clinical practice?

Christine Bestvina, MD: I have used the CASPIAN regimen, durvalumab. Initially, I just wanted to get experience using another drug and to have that experience in my back pocket. Looking at the clinical trials, I don’t find that there’s a huge difference between the trials as far as efficacy or patient selection for 1 drug over the other. What it does is it gives me a second large randomized trial that has a positive outcome, to ensure that this is a really positive benefit of the addition of checkpoint inhibition in addition to chemotherapy for these patients with extensive-stage small cell.

Suresh Ramalingam, MD: One of the things that was different between these 2 trials was 1 of the studies, the CASPIAN, allowed both cisplatin and carboplatin use. What extent does having cisplatin or carboplatin in the combination regimen influence the outcomes in your impression?

Christine Bestvina, MD: To me, it allows for additional provider input and additional provider decision-making in that capacity. If you had a very compelling reason why you wanted to use cisplatin over a carboplatin for, let’s say, less myelosuppressive activity or some other reason, it gives you that option. That’s just nice to have as a provider, to have as many options in your arsenal as possible.

Suresh Ramalingam, MD: Absolutely. One thing I would say, when you look at the results of both of these trials, the numbers look like what we talked about earlier in non–small cell lung cancer: very similar in terms of clinical benefit with PFS [progression-free survival] results. I would also add in the pembrolizumab trial reported at ASCO [American Society of Clinical Oncology Annual Meeting] by Charlie Rudin and the ECOG-ACRIN trial reported by Dr Ticiana Leal with nivolumab in combination with chemotherapy. Just about every 1 of these studies showed very similar overall survival and hazard ratios. Technically, the pembrolizumab trial did not meet the statistical significance for overall survival, but if you look at the hazard ratio, it’s not very different from what we’ve seen with other drugs. In the randomized phase 2 chemotherapy-plus-nivolumab regimen, once again we saw very favorable PFS and overall survival results. These drugs in combination with chemotherapy are behaving differently, and as it was pointed out—Steve, you mentioned this—the benefit is modest. Still, we have a lot of work to do, and 1 possible approach is biomarkers. Are there biomarkers that can be used?

Transcript Edited for Clarity

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