Activity of lurbinectedin as single agent and in combination in patients with advanced small cell lung cancer (SCLC)

Abstract

Background: Lurbinectedin (PM01183, L) is a novel anticancer drug that inhibits activated transcription, inducesDNA double-strand breaks generating apoptosis, and modulates tumormicroenvironment. Relapsed SCLC still remains an unmet medical need. Methods: Antitumor activity and safety of Lurbinectedin in SCLC was reviewed in three clinical trials (n=83 patients): two phase I in combination with doxorubicin (L+DOX; n=48, two cohorts) or paclitaxel (L+TAX, n=7), and a phase II singleagent basket trial (n=28). Results: Median age was similar in these three studies. CNS was involved in 33% (L+DOX cohort A), 4% (L+DOX cohort B), 29% (L+TAX) and 0% of patients (L alone). Patients with sensitive disease were 52%, 64%, 71% and 71%, respectively. Activity was seen in the three studies (see Table). The most reported toxicity was hematological (G3-4 neutropenia/thrombocytopenia/febrile neutropenia: L+DOX Cohort A 96%/34%/34%; L+DOX Cohort B 89%/11%/14%; L+TAX 86%/0%/14%, and L alone 32%/4%/4%). Non-hematological toxicity was mainly G1-2 and included fatigue, nausea/vomiting, and transaminase increase. Conclusions: Lurbinectedin shows activity as a single agent and in combination with other agents (DOX and TAX) in relapsed SCLC. Results were remarkable in terms of PFS, DCR and duration of response, especially in platinum-sensitive SCLC. Toxicity mainly consisted of transient myelosuppression, which was manageable with dose reductions and G-CSF use. A randomized Phase III with L+DOX is ongoing (ATLANTIS Study). (Table Presented).