Lurbinectedin, a selective inhibitor of oncogenic transcription, has activity when given as second-line therapy in patients with relapsed small-cell lung cancer (SCLC).
Lurbinectedin (Zepzelca tradename name) is approved for the treatment of adult patients with metastatic small cell lung cancer with disease progression, following platinum-based chemotherapy.
Results from the phase 2 trial showed that treatment with lurbinectedin led to an overall response rate of 35.2% in these patients.
A median duration of response of 5.3 months was reported.
Participants received 3.2 mg/m2 of lurbinectedin as a 1-hour intravenous infusion once every 3 weeks until either progressive disease or unacceptable toxicity.
The majority of the patients, or 65%, experienced a reduction in tumor size.
Responses were reported in 5 of 8 patients in whom prior immunotherapy had failed.
A total of 26.7%, experienced disease progression and 5 patients were not evaluable.
Response rates with lurbinectedin were higher in patients with platinum-sensitive disease: the ORR was 45% versus just 22.2% in those with platinum-resistant disease.
The median progression-free survival (PFS) was 3.9 months months and the 6-month PFS rate was 33.6%.
In those with platinum-sensitive disease, the median PFS was longer than
those with platinum-resistant disease:in platinum sensitive, the median OS was 11.9 months versus 5.0 months patients who were platinum resistant.
At a median follow-up of 17.1 months, the median overall survival with lurbinectedin was 9.3 months and the 12-month OS rate was 34.2%.
Adverse events: fatigue (51.4%), nausea (32.4%), decreased appetite (21.0%), vomiting (18.1%), diarrhea (12.4%), constipation (9.5%), and neutropenia (5.7%).
The most commonly reported grade 3/4 adverse events were hematologic abnormalities, including anemia (9%), leucopenia (29%), neutropenia (46%), and thrombocytopenia (7%).
In a cohort of 105 patients, responded to treatment at a median follow-up of 17.1 months.
All responses were partial responses (PR), but response rates were higher in patients who had chemotherapy-sensitive disease compared to those with chemotherapy-resistant disease.
The median duration of response was 5.3 months and almost two-thirds of the group at 65% had a reduction in target lesions.
Presently, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC.
Lurbinectedin was given at a dose of 3.2 mg/m2 in a one-hour intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.
60 0f 105 patients had a chemotherapy-free interval of 90 days or longer.
The overall response at only 15% among patients with chemotherapy-resistant disease at a median duration of 4.8 months.
Grade 3 and 4 adverse events (AEs) were most commonly hematologic in nature including neutropenia in 46%, leucopenia in 29%, anemia in 9%, thrombocytopenia in 7% and febrile neutropenia in 5%.