Lurbinectedin Receives FDA Approval for Small Cell Lung Cancer Treatment

On 15 June 2020, approval was granted by the United States Food and Drug Administration (FDA), metastatic (advanced-stage) small cell lung cancer being the indication for lurbinectedin (Zepzelca), an anticancer drug, for use in patients whose cancer had progressed after platinum-based chemotherapy.

Small cell lung cancer is an aggressive type of cancer that accounts for approximately 15% of all lung cancer cases and affects nearly 300 thousand people worldwide each year. However, treatment options for small cell lung cancer are limited, and no new anticancer drugs other than immunotherapies had been approved in the past 20 years.

The efficacy of Lurbinectedin in small cell lung cancer was tested in a multicenter, multicohort clinical study involving 105 patients with metastatic small cell lung cancer. During the study, researchers administered intravenous (into a vein) lurbinectedin every 21 days until cancer progression or unacceptable adverse effects were observed.

The study's primary endpoint was defined as the overall response rate.

Results

• The overall response rate in the 105 patients included in the study was 35%.
• The median duration of response was 5.3 months.
• The independent review committee determined an overall response rate of 30% and a median duration of response of 5.1 months.
• A notable result of the study was a significantly higher overall response rate in platinum-sensitive patients: 45%. In platinum-resistant patients, it was lower: 22%.
• In a further analysis, among 37 patients who had an objective response to lurbinectedin, median overall survival was a little over 1 year (12.6 months), but it was longer in patients with platinum-sensitive disease (15.8 months) and shorter in those with platinum-resistant disease (10.9 months).

The most commonly observed (≥20%) adverse effects, including laboratory abnormalities, were myelosuppression (bone marrow suppression), fatigue, increased creatine, alanine aminotransferase and glucose, nausea, decreased appetite, musculoskeletal pain, reduced albumin, constipation, shortness of breath, reduced sodium and magnesium, increased aspartate aminotransferase, vomiting, cough and diarrhea.

Lurbinectedin was approved under the accelerated approval program because of its unexpectedly positive results in overall response rate and duration of response. The study was conducted under the FDA's ‘Orbit Project’. Through this project, studies are submitted and reviewed simultaneously with international partners. Working with Australia's Therapeutic Goods Administration (TGA), the FDA approved the drug 2 months before its scheduled date.

How does lurbinectedin exert its anticancer effect?

Lurbinectedin acts on the excessively activated DNA synthesis that enables small cell lung cancer cells to multiply very rapidly, causing breaks in double-stranded DNA and apoptosis (programmed cell death), thereby producing an anticancer effect.

Lurbinectedin is a synthetic analogue of a marine compound isolated from the sea squirt Ecteinacidia turbinata, a type of marine animal (pictured above), namely ET- 736. Another cancer drug, trabectedin, used to treat sarcomas, was also isolated from Ecteinacidia turbinata.