e20632 Background: Lurbinectedin is a selective inhibitor of oncogenic transcription. The US FDA granted accelerated approval for lurbinectedin as monotherapy (3.2 mg/m2 q3wk) for relapsed small cell lung cancer (SCLC) based on a phase 2 basket trial (NCT02454972). The ATLANTIS trial (NCT02566993) investigated lurbinectedin 2.0 mg/m2 plus doxorubicin 40.0 mg/m2 q3wk versus topotecan or CAV in relapsed SCLC. The CORAIL trial (NCT02421588) evaluated lurbinectedin (3.2 mg/m2 i.v. q3wk) compared to pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer. The elderly population is usually under-represented in clinical trials despite its interest due to the increased frailty and high comorbidity. Methods: Data from Basket and CORAIL trials were included in an integrated safety analysis to evaluate lurbinectedin safety profile at the approved regimen (3.2 mg/m2 q3wk). This post hoc safety analysis compares the outcomes of lurbinectedin in elderly population (n = 207 patients ≥65 years old; Basket n = 113 and CORAIL n = 94) versus topotecan (n = 75 patients ≥65 years old; ATLANTIS n = 45 and CORAIL n = 30). Results: Treatment-related adverse events (AEs) and laboratory abnormalities regardless of relationship occurring in > 10% of patients, were: Compared with topotecan, lurbinectedin showed lower frequency of treatment-related grade ≥3 AEs (53.1% vs. 85.3%; p < 0.01) and grade ≥3 serious adverse events (SAEs) (19.8% vs. 34.7%; p = 0.01) and a trend for less AEs leading to treatment discontinuation (5.3% vs. 8.0%; p = 0.40) or deaths (1.4% vs. 5.3%; p = 0.08). Use of supportive treatments was significantly lower with lurbinectedin: G-CSF (17.9% vs. 29.3%; p < 0.05), red blood cells transfusions (20.8% vs. 56.0%; p < 0.01) or erythropoietin (2.4% vs. 14.7%; p < 0.01). Conclusions: Lurbinectedin is well tolerated in elderly patients and has a predictable and manageable safety profile. No new safety signals were observed. With the limitations of cross-trial comparisons, lurbinectedin shows a clear advantage in terms of hematological toxicity compared with topotecan in patients ≥ 65 years old. Furthermore, fewer elderly patients treated with lurbinectedin had severe AEs, SAEs, treatment discontinuations and deaths compared to elderly patients treated with topotecan. Clinical trial information: NCT02454972 , NCT02566993 , NCT02421588 . [Table: see text]