Lurbinectedin was added to the Clinical Practice Guidelines in Oncology by the National Comprehensive Cancer Network on July 7, 2020 for the treatment of patients with small cell lung cancer.
Lurbinectedin (Zepzelca) was added to the Clinical Practice Guidelines in Oncology by the National Comprehensive Cancer Network (NCCN) on July 7, 2020 for the treatment of patients with small cell lung cancer (SCLC), according to a press release from Jazz Pharmaceuticals.1
The guidelines recommend the therapy for patients with SCLC who relapse 6 months or sooner after prior systemic therapy, as well as for patients who relapse more than 6 months after prior systemic therapy. The guidelines state that lurbinectedin is a preferred regimen for patients who relapse 6 months or less after prior systemic therapy.
“We appreciate the decision by the NCCN to quickly incorporate Zepzelca into the Clinical Practice Guidelines in Oncology as it supports our commitment to ensuring that patients with relapsed small cell lung cancer are able to access this important new treatment option,” said Robert Iannone, MD, MSCE, the executive vice president of Research and Development at Jazz Pharmaceuticals in the press release. “Zepzelca has the potential to fill an unmet need in relapsed SCLC where treatment options have been limited.”
Lurbinectedin was granted an accelerated approval by the FDA on June 15, 2020 for the treatment of adult patients with metastatic SCLC who experienced disease progression on or after platinum-based chemotherapy.
Under the “Accelerated Approval” Program, therapies that fill an unmet need for serious or life-threatening diseases or conditions are able to receive conditional approval.
The approval was based on findings from an open-label, single-arm, phase 2 basket study (NCT2454972), in which patients with SCLC who progressed on platinum-based chemotherapy received a 1-hour intravenous infusion of 3.2 mg/m2 of lurbinectedin every 3 weeks until progressive disease or unacceptable toxicity.
The results showed that, of 105 patients, lurbinectedin led to a 35.2% investigator-assessed overall response rate (ORR). Thirty-seven patients derived a partial response. Additionally, 35 patients had stable disease, which translated to a 68.6% disease control rate (95% CI, 58.8%-77.3%).2
The ORR was 30% per independent review committee.
The median duration of response per investigator assessment was 5.3 months (95% CI, 4.1-6.4) and 5.1 months per independent review committee.
“The second-line setting of SCLC is a very challenging one clinically,” said Jacob Sands, MD, a physician at Dana-Farber Cancer Institute and an instructor of medicine at Harvard Medical School, in an interview with OncLive. “These are patients with resistant, rapidly progressing disease, and often declining functional status. We don’t really have many treatment options in that space. [Topotecan] is an FDA-approved option that unfortunately is often difficult to tolerate. Now [we] have an FDA-approved option in lurbinectedin that is generally well tolerated with some durable efficacy. Many patients will have some response to [lurbinectedin], which is a very compelling treatment that has been [sorely] needed.”
Regarding safety in the phase 2 trial, the agent was generally well tolerated. Any-grade adverse effects (AEs) were observed in 84.8% of patients. The most common grade 1/2 AEs included fatigue (51.4%), nausea (32.4%), decreased appetite (21.0%), vomiting (18.1%), diarrhea (12.4%), constipation (9.5%), and neutropenia (5.7%).
Grade 3 or higher AEs that were mainly hematologic in nature were reported in 34.3% of patients, 10.5% of which were serious treatment-related AEs (TRAEs). Of these events, neutropenia and febrile neutropenia were observed in 5% of patients, each. No AE-related deaths were reported.
“Generally, [lurbinectedin] was a very well-tolerated drug, which is important in this clinical situation” said Sands. “Even in the patients who ended up not benefitting from the drug, [we] are not really harming them in the process. That is an important thing to consider in this patient population where it is so challenging to treat [patients]. Of course, we want to make sure that the [AEs] are not worsening patients’ quality of life.”
Less than 2% of patients who received lurbinectedin discontinued the drug due to AEs. Additionally, 22.1% and 26.3% of patients required dose delays and dose reductions, respectively.
The accelerated approval allowed Jazz Pharmaceuticals to make lurbinectedin commercially available in the United States in July 2020. Continued approval for the indication will be contingent on the results of a confirmatory trial.
Based on the positive findings from the phase 2 study, lurbinectedin is being evaluated in combination with doxorubicin as a second-line treatment for patients with SCLC in the ongoing randomized phase 3 ATLANTIS trial (NCT02566993).