Treatment After Progression of SCLC: Lurbinectedin

Hossein Borghaei, DO, MS: We’re going to move on to the second segment of the study, which has to do with relapsed/refractory small cell lung cancer. We’re going to discuss some treatment options for patients who have evidence of disease progression following what we just talked about: chemotherapy and immunotherapy. We’re also going to talk about a couple of approved drugs. Vivek, lurbinectedin has received a lot of attention lately. I’m wondering if you can cover some of the data and recent information that have been published and discussed at various meetings.

Vivek Subbiah, MD: Thank you so much, Hoss. As we all know, few options exist for patients with small cell lung cancer after failure of first-line therapy. Lurbinectedin was interesting as a selective inhibitor of oncogenic transcription. I mainly got involved in the trial because it was active in multiple small round blue cell tumors, including Ewing sarcoma. The phase 2 study that was designed was a basket study. Small cell was one of the arms of this basket study. They evaluated the safety and activity of lurbinectedin in patients with small cell lung cancer after failure of platinum-based chemotherapy. This was a simple single-arm, open-label, phase 2 basket study. They recruited patients from mainly Europe and the United States. Patients had to have an ECOG PS [performance status] of less than 2 in the absence of brain metastasis, and adequate organ function. Treatment consisted of lurbinectedin monotherapy at 3.2 mg/m2 as a 1-hour intravenous infusion every 3 weeks until disease progression.

Between October 2015 and January 2019, 105 patients were enrolled and treated on the lurbinectedin study. The median follow-up was 17.1 months. An overall response by investigator assessment was seen in 37 patients, for an objective response rate of 35.2%. The most common adverse events we saw were hematologic abnormalities, as this is chemotherapy; namely anemia in 9% of patients; low white blood cell count, leukopenia, in around 30% of patients; neutropenia in 46% of patients; and thrombocytopenia in 7% of patients. There were no treatment-related deaths reported. Lurbinectedin was active in the second line of therapy of small cell lung cancer in terms of overall response rate and had an acceptable and manageable safety profile.

Lurbinectedin could represent a potential new treatment option for patients who have very few options when they relapse. This is being investigated both as monotherapy and in combination. What is the value of this monotherapy arm of this basket study? It provided the first clinical evidence of an agent with antitumor activity as a single drug in patients with relapsed small cell lung cancer, with durable responses. The results detected by the investigator assessment were robust and confirmed by independent central review as well. Lurbinectedin appeared to be a valuable treatment option. The benefits from the lurbinectedin study appear to be favorable compared with what we historically see with topotecan, which is the standard of care, in terms of both antitumor activity and safety.

This drug profile is relevant for patients with small cell lung cancer who have a very dismal prognosis. The NCCN [National Comprehensive Cancer Network] recommends a rechallenge with first-line treatment for relapsed small cell lung cancer with a chemotherapy-free interval of greater than 180 days. From this phase 2 basket study, activity was shown in this setting as well for lurbinectedin. We recently reported a preplanned analysis from this subtype. Interestingly, the investigator-assessed objective response rate in this cohort was 60%, with a median duration of 5.5 months and disease control rate of 95%. Interestingly, with the censoring of 53%, the median overall survival was 16.2 months. Of note, 60.9% and 27.1% of patients were alive at 1 and 2 years, respectively.

The most common treatment-related adverse events were hematologic disorders. Neutropenia was seen in 55% of patients, anemia in 10% of patients, and thrombocytopenia in 10% of patients. Increases in AST [aspartate aminotransferase] and AFP [alpha-fetoprotein] were noted in around 5% to 10% of patients. Interestingly, no cases of febrile neutropenia were reported.

What did it show? Lurbinectedin is an effective treatment for platinum-sensitive relapsed small cell lung cancer, especially in patients with a chemotherapy-free interval of greater than 180 days, with an acceptable safety profile. These encouraging results suggest that lurbinectedin can be another valuable tool in our arsenal and a therapeutic option rather than platinum rechallenge in these patients.

Hossein Borghaei, DO, MS: We’re going to come back to a couple of discussion points.

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