Dr Apar Kishor Ganti Explains Why Lurbinectedin Is Exciting for Patients With SCLC

November 1, 2020

With few treatment options in small cell lung cancer, lurbinectedin was quickly added to the National Comprehensive Cancer Network’s guidelines after the FDA approved it, said Apar Kishor Ganti, MD, of University of Nebraska Medical Center.

With few treatment options in small cell lung cancer, lurbinectedin was quickly added to the National Comprehensive Cancer Network’s (NCCN) guidelines after the FDA approved it, said Apar Kishor Ganti, MD, professor of internal medicine, Division of Oncology & Hematology, University of Nebraska Medical Center.

Lurbinectedin is a selective oncogenic transcription inhibitor that is being studied in 9 different tumor types. Can you discuss the mechanism of action, and why it offers promise for certain patients when a first-line therapy fails?

Lurbinectedin inhibits oncogenic transcription. Basically, what it does is it prevents the binding of the transcription factors to their sequences, and therefore, it prevents transcription which is responsible for cell division and eventually leads to cell death or apoptosis. In addition to blocking this in tumor cells, it also inhibits transcription in the tumor-associated macrophages and therefore it can affect the tumor microenvironment as well.

The reason it is important or exciting is because there was a new trial that was just published recently in The Lancet, where they looked at lurbinectedin, in small cell lung cancer. Like you said, it's been studied in other tumor types as well. But this was a report specifically in small cell lung cancer, and in that group of patients, about 35% of the entire population responded to this. And these were patients who had previously received at least one line of chemotherapy. And historically in that cohort of patients, the response rates range anywhere between 15% and 20%. So, when this study reported a 35% response rate, automatically, that became pretty big news.

What is the NCCN guidelines recommendation for lurbinectedin?

So NCCN guidelines recommend lurbinectedin in the relapse setting, meaning patients who have failed at least one previous line of chemotherapy, and it is the second drug that has been FDA approved in this setting after topotecan. And so the NCCN guidelines recommend that as preferred option in patients who have failed small cell lung cancer…and it has been about more than 3 months since their previous treatment. So chemotherapy-free interval of 90 days. For the other group for patients with a chemotherapy-free interval of less than 90 days, it is an option.

Lurbinectedin was added to the guidelines less than a month after the therapy was approved under an accelerated approval: What is the importance of NCCN adding lurbinectedin to the guideline so quickly?

As I said earlier, there's not too many good treatment options for these patients. Topotecan is currently the, or was currently, the only approved indication in this setting. And topotecan had a lot of problems with side effects and patients not tolerating it. So, this provides a very important option for patients who are in this setting, meaning people who have failed one line of chemotherapy for small cell lung cancer and currently have relapsed disease. So, it becomes an important option for this group of individuals.

And the reason NCCN approved it so rapidly was that it recognizes the fact that there were not too many treatment options for these patients. And this represented an important advance.