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Overview of Second-Line Treatment Options in SCLC
Expert oncologists Laurent Greiller, MD, and Christian Grohé, MD, reflect on the current state of second-line treatment options for patients with small cell lung cancer.
Transcript:
Laurent Greillier, MD, PhD: We are going to discuss the current and the emerging treatment options for relapsed/refractory small cell lung cancer. The first question I have, Dr Grohé, could you briefly discuss the general second-line and subsequent treatment options for small cell lung cancer?
Christian Grohé, MD: Yes, I think this is a very important issue. We don’t really have good data for second-line treatment options. As you have mentioned before, the sequence of treatment is very important in lung cancer. We have found another clinical signal to be important, and that’s time to progression. It used to be the standard of care after 4 to 6 cycles of first-time therapy, you stopped treating the patient and then you did the follow-up controls. Once the patient had another relapse, then you started to treat this patient again, depending on the time to progression. So, more than 6 to 9 months, you would rechallenge the patient with the standard of care, platinum-based chemo with etoposide; less than that you would go for drugs, which would include topotecan, or all the drugs in a combination like doxorubicin or other anthracyclines of that case. In some countries we have an approval for IO drugs and in some countries we do not have that. I won’t go into much detail about that.
In general, now we have a different kind of situation because our patient will receive maintenance therapy, which consists of a maintenance of IO drugs. We do see a new concept, which we should take into consideration how to treat these patients if they progress or have a major relapse while they’re on IO. That’s the idea, the label of IO is until progression, so now we have to come up with a new kind of sorting out what patient would have a benefit. Another indicator would be is that multisite progression or is that a single-site metastasis we might treat locally, or we can use radiotherapy. What is your general approach to small cell lung cancer treatment options in the relapse/refractory setting? What is important to guide selection in this cohort?
Laurent Greillier, MD, PhD: I would say that beyond the classical prognostic factors such as age, performance, size and so on, as you mentioned then what is very important probably in the second-line setting is to consider what was the response to treatment in the first-line setting, and then what was the treatment-free interval. This notion of treatment-free interval is related to the platinum exposition historically. This topic is also a little bit changing today when patients receive maintenance immunotherapy. For the time being, we are keeping in mind this concept that patients who experience relapse of the disease in the first 3 months or 90 days after the end of platinum are considered as platinum resistant. You release patients who are treated in the second line with different drugs from the first line. So, the topotecan therapy, the treatment with the three cycle, the CAV, cyclophosphamide, doxorubicin, and vincristine, with our historical second-line treatment for small cell lung cancer patients. For patients with disease relapse beyond the 3 months of stopping the chemotherapy with platinum, we call them “platinum sensitive.” For these patients that are suggesting that we can rechannel these patients with a first-line regimen with, again, platinum plus etoposide, then usually that’s what we are doing in France. I don’t know, in Germany, if you are globally using the same approach?
Christian Grohé, MD: Yes, we do the same approach. There has been a new kid on the block, which has been tested in ovarian cancer, called lurbinectedin. Lurbinectedin now has approval for second-line or relapsed small cell lung cancer in some countries, for instance, in the United States. I think in some European countries [it is] undergoing the review process. We are still awaiting the option to use this drug. Lurbinectedin is an interesting drug in terms of, it doesn’t have a different kind of mode of action. It’s just like an RNA polymerase modulator, which ultimately leads to the inhibition of transcription of respective parts that leads to cell death. What might be of importance is that it might change the tumor micromilieu. It might be modulated, so it might be a good partner for patients who have seen IO in the first line. As I mentioned before, there’s this IMforte trial [NCT05091567] and the IMforte trial is still enrolling until the end of the year. We do have lurbinectedin in some countries, at least for second lines, where we could use that drug for patients where it has been approved.
Transcript edited for clarity.
