Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial.

Abstract

8506 Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC cohort, a target ORR ≥30% was set. One-hundred and five patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line were treated with L 3.2 mg/m2 as a 1-hour i.v. infusion on Day 1 q3wk. Results: Median age was 60 years (range, 40-83), 60% were male, ECOG PS 0/1/2 (32%/62%/6%), liver metastasis 41%, history of CNS involvement 3.8%, prior platinum 100%, median chemotherapy-free interval (CTFI): 3.5 (0-16.1) months; prior immunotherapy (IO): 7.6%. Pts received a median of 4 cycles (range, 1-24). Conclusions: L monotherapy is active in second-line SCLC in both resistant and sensitive disease. The acceptable and manageable safety profile is also associated to a convenient treatment administration (Day 1 q3wk). L as second-line treatment in SCLC emerges as a new promising drug for this unmet clinical need. Clinical trial information: NCT02454972. [Table: see text]

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

“…Grade 3-4 adverse events included neutropenia (22.9%), anaemia and fatigue (6.7% each), febrile neutropenia and thrombocytopenia (4.8% each). 27 To date, topotecan remains the only drug approved for relapsed SCLC patients, based on the results of different Phase 2-3 trials that showed a response rate of 7-38% among sensitive patients and of 2-7% among refractory ones. [5][6][7]28,29 A recent meta-analysis described clinical outcomes of 1347 SCLC patients treated with topotecan from 14 prospective trials.…”

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

“…A novel cytotoxic drug is lurbinectedin, a transcription inhibitor that binds to the DNA minor groove and inhibits RNA polymerase II; is active as a single agent in secondline SCLC in a phase 2 trial for both sensitive and resistant disease (ORR 35.2%) [33], a phase 3 study in combination with doxorubicin vs chemotherapy has completed the recruitment, pending of final results (ATLANTIS trial).…”

<p>Orphan Drugs in Development for the Treatment of Small-Cell Lung Cancer: Emerging Data on Lurbinectedin</p>

“…Patients with CNS metastases were excluded from the study. The overall 29 Patients with sensitive disease had a better response and outcome than patients with resistant disease. For comparison, the pivotal study of topotecan, the current standard in second line treatment in relapsed disease, revealed an ORR of 24.3%, a median PFS of 13.3 weeks, and a median OS of 25.0 weeks.…”