Second-Line Treatment Recommendations for ES-SCLC


Hossein Borghaei, DO, reviews the second-line treatment options in the setting of extensive-stage small cell lung cancer: topotecan or lurbinectedin.

Hossein Borghaei, DO: What happens when there’s evidence of progression? In our case, roughly 5 months after starting treatment, patients began to complain of some fatigue. He felt that he had wheezing. There was unintended weight loss, increasing shortness of breath, some right upper-quadrant pain, and back pain. CT confirmed that the liver metastases were unfortunately progressing, indicating the patient was no longer responding to the checkpoint inhibitor that the patient was receiving as maintenance therapy.

The question is what can be done and what should be our standard approach. This gets to be a bit of a discussion. We have drugs that are approved in this setting. Some of these drugs are familiar to you. Topotecan has been around for a long time. We have lurbinectedin, another drug that’s been FDA approved and can be used in a setting like this. We also get into this discussion of chemotherapy-sensitive vs chemotherapy-resistant disease in small cell [lung cancer]. The definition is an old 1, goes back many years, and it has to do with how long after initial chemotherapy a patient was able to maintain a response. This 90-day, 3-month a time frame has emerged as an indication whether somebody has chemotherapy-sensitive or chemotherapy-resistant disease. The definition matters because for patients who unfortunately have chemotherapy-resistant disease or patients with metastatic small cell who have treatment-refractory disease, that means that despite the best treatment that we have, the first CT shows evidence of disease progression. Unfortunately, they don’t do well with subsequent standard treatment options that we have right now, so the response rates tend to be a little bit lower.

Chemotherapy-sensitive patients, if you go by the 90-day time frame, can have a better response rate to subsequent treatment as opposed to chemotherapy-resistant patients. At least before the era of having checkpoint inhibitors in immunotherapy drugs, a chemotherapy-sensitive patient could sometimes get a repeat of the same chemotherapy they got in the beginning. The question is do we go back to that, and that’s a practice decision everyone has to make in conjunction with all the other data available: Is the patient healthy enough to get another platinum-based treatment? What are the real data around that?

For the purpose of our discussion, I’d like to suggest that in this case, given all the symptoms, I would like to move on to another form of treatment. As I said, that’s based on what we have available. The options are topotecan vs this newer drug, lurbinectedin. Topotecan we all have worked with in the past. It’s an inconvenient drug to use. It requires repeat visits to the infusion room and is highly myelosuppressive. The outcomes, unfortunately, haven’t been all that good. Lurbinectedin is a newer drug. It has an interesting mechanism of action. It has been postulated that it could have a couple of ways of affecting the tumor or the tumor microenvironment, making it a drug that we might have an interest in, for the development and what to do with it down the road in terms of combination studies.

What do we do in a case like this, and how do we proceed in second-line treatment? If we don’t rechallenge with the initial chemotherapy, the option of using a drug like lurbinectedin makes sense.

Transcript edited for clarity.

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