medwireNews: The ATLANTIS trial has found no significant overall survival (OS) improvement with the combination of lurbinectedin and doxorubicin versus chemotherapy in previously treated patients with small-cell lung cancer (SCLC).
“Although the primary objective of this study was not met, the combination […] was active in patients with SCLC after failure of one prior platinum-containing line, especially in those with sensitive disease […] and without central nervous system [CNS] involvement at baseline,” presenting author Luis Paz-Ares (Hospital Universitario 12 de Octubre, Madrid, Spain) told the press at the IASLC 2021 World Conference on Lung Cancer.
He continued: “Novel combinations of lurbinectedin with other cytotoxics such as irinotecan or checkpoint inhibitors such as atezolizumab are being explored.”
The randomized phase 3 study enrolled 613 patients who had received one line of chemotherapy for limited- or extensive-stage SCLC and had a chemotherapy-free interval (CTFI) of at least 30 days. Participants in the experimental arm received lurbinectedin 2 mg/m2 plus doxorubicin 40 mg/m2 every 3 weeks, while those in the control arm could receive either topotecan 1.5 mg/m2 on days 1–5 of every 21-day cycle or cyclophosphamide 1000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg every 3 weeks.
The primary endpoint of OS did not differ significantly between the lurbinectedin–doxorubicin group and the control group in the overall trial population, at a median of 8.6 and 7.6 months, respectively, and there was also no significant difference between treatments in any subgroup.
Lurbinectedin plus doxorubicin appeared to reduce the risk for progression for death by a significant 17% relative to the control regimen, but the median progression-free survival (PFS) durations were identical, at 4.0 months.
The PFS benefit associated with the lurbinectedin combination was especially pronounced in the subgroup of patients with a CTFI greater than 180 days and those without baseline CNS metastases, with significant hazard ratios for progression or death of 0.47 and 0.79, respectively.
Paz-Ares also reported on the objective response rate, which was comparable between lurbinectedin-treated participants and those given the control regimen (31.6 vs 29.7%) in the overall study population, but was higher with lurbinectedin among those with a CTFI longer than 180 days (41.9 vs 29.2%).
The safety data favored the lurbinectedin arm over the control arm even though primary prophylaxis with granulocyte-colony stimulating factor was mandatory in both groups, with lower rates of adverse events of at least grade 3 (47.2 vs 75.4%), as well as dose delays (26.1 vs 34.3%), reductions (21.8 vs 47.8%), discontinuations (7.6 vs 15.6%), and deaths (0.3 vs 3.5%) due to adverse events.
Of note, the incidence of hematologic toxicities of grade 3 or worse was significantly lower in the lurbinectedin than control group. For instance, the respective rates of thrombocytopenia of this severity were 13.9% and 31.1%, while anemia occurred in 14.5% and 31.1% of patients and neutropenia in 37.0% and 69.2%.
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