VIDEO: Determining optimal treatment strategies for small cell lung cancer

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Determining the optimal treatment strategy is such an important thing at every step of the way, and there is no optimal that you can outline starting at the very beginning. The optimal treatment for metastatic small cell lung cancer in the first-line setting is chemotherapy plus immunotherapy. A subset of those people will have many years of disease control. Of course, we hope for that for everybody, but we know that in the majority of patients, they’re going to end up with months of control.

Now, the chemotherapy-free interval becomes a really important consideration when talking about second-line treatment options. Those with a longer chemotherapy-free interval are more likely to benefit from cytotoxics, in general. We often talk about retreatment with platinum-etoposide. That’s not something that I do a lot of. I often will go on to other cytotoxics, which tend to be better tolerated than platinum-etoposide. Although, platinum-etoposide continues to be an option that you can consider coming back to in someone who’s had a particularly durable response in the first-line setting. But a long chemotherapy for your interval means that other cytotoxics are more of an option.

You are more likely to get durable responses when there’s been a durable response in the first-line setting. If the patients have not gotten atezolizumab (Tecentriq, Genentech) or durvalumab (Imfinzi, AstraZeneca) in the first-line treatment, which is something that can come up particularly if they had limited-stage disease, so they have chemo and radiation and now have recurrence, but if they never got a checkpoint inhibitor, I really try and make sure that they get one. Previously, there was accelerated approval for pembrolizumab (Keytruda, Merck) and nivolumab (Opdivo, Bristol Myers Squibb). They had first-line trials that were negative, and so, they really have not been pursuing the full FDA approval.

But in the third-line setting in single-arm trials, we did see a subset of patients with very durable responses. With pembrolizumab, we saw a response rate of 19% but 13% with ongoing disease control beyond 2 years, which is to say that this is a very important treatment option for patients that have not gotten that.

Now, in those with a short chemotherapy-free interval, the likelihood of benefiting from cytotoxics really drastically drops. And the importance of clinical trials cannot be understated for all of these patients. But especially those with a short chemotherapy-free interval, they’re unlikely to benefit from the other cytotoxics that are approved, being lurbinectedin. Topotecan is only approved for chemotherapy-free interval of more than 45 or 90 days, whether you’re looking at PO or IV, but you’re not likely to get really much durability from those. And so clinical trials are really a particularly important consideration.