Switching to Lurbinectedin Monotherapy Maintains, Improves Tumor Response for Relapsed Small Cell Lung Cancer
Investigators reported that individuals who completed 10 cycles of lurbinectedin and doxorubicin who then switched to lurbinectedin as a monotherapy tended to have maintained or improved tumor response.
Individuals with relapsed small cell lung cancer (SCLC) who completed 10 cycles of lurbinectedin (Zepzelca; Jazz Pharmaceuticals) and doxorubicin (Adriamycin; Pfizer) combination and switched to lurbinectedin as a monotherapy tended to have a tumor response that was maintained or improved, according to a session at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Lurbinectedin, a selective inhibitor of oncogenic transcription, had received accelerated approval from the FDA in June 2020 as a monotherapy for adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy.
Data from the phase 3 ATLANTIS trial that showed the overall response rate (ORR) to this regimen in 105 trial participants was 35.2% with the duration of response (DOR) at 5.3 months. During the trial, the investigators examined the combination of lurbinectedin at 2.0 mg/m2 and doxorubicin at 40.0 mg/m2 given intravenously when compared to treatment with topotecan.
Specifically, the investigators aimed to assess the efficacy and safety of lurbinectedin as a single agent in individuals who completed 10 cycles of the combination and then switched to lurbinectedin as a monotherapy.
During the patient selection process, investigators included individuals aged 18 years or older with limited-stage or extensive-stage SCLC who had 1 prior line of platinum-based chemotherapy, including PD-1/PD-L1 inhibitors, ECOG PS of 2 or less, and who were chemotherapy-free at an interval of 30 or more days. An independent review committee assessed tumor response.
The median age of individuals in the study was 61.5 years old, ranging from 43 to 77. The overall median number of treatment cycles was 15, ranging from 11 to 47, and included a median of 5 cycles on monotherapy. The majority of individuals who switched to lurbinectedin monotherapy were found to either have a maintained or improved tumor response.
All 3 individuals who achieved a complete response (CR) on the combination therapy maintained that response on monotherapy. Of the 26 individuals with a partial response (PR) on combination therapy, 12% achieved a CR and 15% maintained their PR.
Of the 19 individuals with stable disease (SD) on combination therapy, 3 improved to PR and 8 maintained SD. The median DOR was 8.3 months, and the median overall survival (OS) was 20.7 months.
Based on laboratory assessments, grade 3 and 4 hematologic abnormalities noted during the trial included anemia, leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Additionally, febrile neutropenia was reported in 4% of individuals.
Overall, investigators found that switching to the monotherapy resulted in favorable OS and DOR, with acceptable tolerability. Furthermore, no new safety signals were identified during the trial.
Navarro A, Ponce Aix S, Barneto-Aranda IC, Smit EF, et al. Analysis of patients with relapsed small cell lung cancer (SCLC) receiving single-agent lurbinectedin in the phase 3 ATLANTIS trial. Journal of Clinical Oncology. doi:10.1200/JCO.2022.40.16_suppl.8524