Phase II study of sabarubicin (MEN 10755) in newly diagnosed patients with extensive stage small cell lung cancer (ESCLC): Final report

19043 Background: Despite being sensitive to cytotoxic chemotherapeutic agents and the recent development of effective novel targeted therapies for the management of solid tumours little progress has been made in the management of extensive stage small cell lung cancer (ESCLC). Sabarubicin is a third generation anthracycline with improved preclinical efficacy and tolerability, in particular regarding cardiotoxicity, compared to doxorubicin. The aim of this phase II study was to evaluate the efficacy and safety of sabarubicin (MEN 10755 hydrochloride) in chemotherapy naive patients with ESCLC. Methods: Based on Gehan two-stage design principles 14 patients were enrolled in stage 1, with an additional 12 patients in stage 2 of the study. Patients received 80 mg/m2 on day one of a 21 day cycle. Dose escalation to 90 mg/m2 was allowed if patients did not experience >Grade 1 toxicity on the first course. If, at 90 mg/m2, toxicities ≥Grade 2 occurred (excluding alopecia, anemia, and nausea/vomiting) the dose was reduced to 80 mg/m2. Results: Twenty-six patients were enrolled and eligible for efficacy and safety evaluation. Mean age = 63.5 years (range 37–79). Eight patients (30.8%) were ECOG performance status (PS) 0, 13 (50%), PS 1 and 5 (19.2%), PS 2. The tumor response rate (RR) was 38.5% (10/26) (95% CI 22.43 - 57.46), including one complete and nine partial responses. Ten (38.5%) had stable disease and six, (23.1%) progressive disease. The median duration of response was 4.5 months. The median time to tumour progression was 4.2 months and median overall survival, 10.5 months (95% CI 7.8 - 18.1 months). There were no toxicity related deaths. Severe, predominantly haematological, adverse grade 3 or 4 events were observed in 22 (84.6%) patients including febrile neutropenia in two and cardiotoxicity in one which resolved with treatment. Conclusions: Sabarubicin has significant single agent anti-cancer activity, and is well tolerated, in patients with ESCLC. The observed RR compares with other single agents used in ESCLC whilst the median survival observed is consistent with that seen for standard combination therapies. Further studies with sabarubicin, alone and in combination with other cytotoxic and novel targeted agents, are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Menarini Ricercue Menarini Ricercue