Pooled safety analysis of lurbinectedin plus irinotecan in patients with advanced solid tumors.

Lurbinectedin in combination with irinotecan showed synergistic antitumor activity in preclinical studies. A phase I/II trial (NCT02611024) evaluated this combination in patients with advanced solid tumors. The phase II stage evaluated the antitumor activity of the recommended dose (RD) (lurbinectedin 2.0 mg/m2 on Day (D)1 plus irinotecan 75 mg/m2 on D1 and D8 q3wk with primary granulocyte colony-stimulating factor prophylaxis) in five tumor-specific cohorts. This pooled analysis describes the safety profile of this combination from 233 patients with different advanced solid tumors treated at the RD. Adverse events (AEs) and laboratory abnormalities were graded using NCI-CTCAE v.4. The most frequent AEs (any grade) related to treatment were fatigue (71% of patients/25% of cycles), diarrhea (62%/17%), nausea (59%/18%), vomiting (35%/7%) and decreased appetite (32%/6%); the most common grade ≥ 3 AEs were fatigue (14%/2%), diarrhea (14%/2%) and febrile neutropenia (9%/1%). The most common grade ≥ 3 laboratory abnormality regardless of relationship was neutropenia (53%). The rate of discontinuation due to treatment-related AEs was 3% (n = 7 patients). There was one treatment-related death (0.4%) involving a 63-year-old male patient (0.4%) diagnosed with metastatic NEN who died due to grade 5 staphylococcal bacteremia. In conclusion, this pooled analysis shows a predictable and manageable safety profile for lurbinectedin in combination with irinotecan in patients with advanced solid tumors, with myelosuppression, fatigue and gastrointestinal disorders being the main toxicities observed.Trial code: ClinicalTrials.gov identifier: NCT02611024.