Lurbinectedin showed promising activity as a second-line therapy for small-cell lung cancer (SCLC), according to a phase II trial presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (abstract 8506). With activity in both chemo-sensitive and -resistant disease and a manageable safety profile, the agent may represent a new treatment option in this setting.
“SCLC is a very aggressive disease with a dismal prognosis with currently available treatments,” said Luis G. Paz-Ares, MD, PhD, of the Hospital Universitario 12 de Octubre in Madrid. He added that topotecan is the only treatment approved by the US Food and Drug Administration over the last 20 years in the second-line setting.
Lurbinectedin is a potent inhibitor of oncogenic transcription, and it demonstrated antitumor activity in a phase I/II study in combination with doxorubicin. Paz-Ares presented results of the new phase II trial of single-agent lurbinectedin in patients with SCLC who had received one prior line of chemotherapy (prior immunotherapy was allowed).
The study included a total of 105 patients, with a median age of 60 years. Most patients were men (60%), and 7.6% of the cohort had received prior immunotherapy. The median chemotherapy-free interval was 3.5 months, and 20% had received chemotherapy less than 30 days prior to initiating lurbinectedin treatment.
The objective response rate was 35.2%; all responses were partial responses, and another 33.3% of the cohort had stable disease. This resulted in a disease control rate of 68.6%. The median duration of response was 5.3 months. Sixty-five percent of patients saw some decrease in tumor size with lurbinectedin.
Among the 45 patients with resistant disease (defined as a chemotherapy-free interval under 90 days), the response rate was 22.2%. Among the 60 sensitive patients, the rate was 45.0%. The median duration of response in the resistant and sensitive patients was 4.7 months and 6.2 months, respectively.
The median progression-free survival (PFS) was 3.9 months, and the 6-month PFS rate was 33.6%. In resistant patients, the 6-month PFS rate was 18.8%, compared with 44.6% in sensitive patients. The median overall survival (OS) was 9.3 months, with a 12-month OS rate of 34.2%. In resistant and sensitive patients, the 12-month OS rates were 15.9% and 48.3%, respectively.
Most patients experienced an adverse event (AE) of any grade (84.8%), and 34.3% of the cohort had at least one grade 3 or higher AE; serious AEs occurred in 10.5% of the cohort. There were no related AEs leading to death, and only 2 patients had a related AE leading to treatment discontinuation; 22.1% of patients required a dose delay, and 26.3% required a dose reduction. Neutropenia was the most common grade 3/4 AE (22.9%), followed by anemia (6.7%), fatigue (6.7%), thrombocytopenia (4.8%), and febrile neutropenia (4.8%).
“Lurbinectedin is emerging as a potential new treatment alternative for the second-line setting in SCLC patients,” Paz-Ares concluded.
Anna F. Farago, MD, PhD, of Massachusetts General Hospital in Boston, was the discussant for the abstract. She said that the response rate in the trial “does stand out” as a numerically higher value than seen in other SCLC studies. “The OS data are somewhat immature, as a third of patients are still in follow-up,” she noted. “And there are shifting standards for first-line therapy, now with more patients receiving combination chemotherapy and immunotherapy.”
Farago said phase III data on lurbinectedin are still needed to move forward, though no randomized single-agent lurbinectedin studies are planned. One large randomized phase III trial is ongoing that compares lurbinectedin in combination with doxorubicin to either topotecan or cyclophosphamide/doxorubicin/vincristine. “We look forward to seeing those results,” she said.