Lancet Respirat Med: Lurbinectedin in combination with doxorubicin for the treatment of recurrent small cell lung cancer

Lurbinectedin is a synthetic marine anticancer agent that selectively inhibits oncogenic transcription
.
Based on its efficacy in patients with small cell lung cancer (SCLC) who relapses after first-line platinum-based chemotherapy, Lurbinectedin monotherapy (3.
2 mg/m2·3 weeks) received accelerated approval
from the US FDA.
The ATLANTIS trial evaluated the efficacy and safety
of Lurbinectedin plus anthracycline doxorubicin as second-line treatment for SCLC.

This is an open-label, randomized phase 3 trial that recruited patients aged 18 years and older with relapsed SCLC after platinum-based chemotherapy from 135 hospitals in multiple countries
.
Patients were randomized (1:1) to receive Lurbinectedin plus doxorubicin or a physician-selected comratherapy until disease progression or intolerable toxicity
.
The primary endpoint is overall survival
.

From August 30, 2016 to August 20, 2018, a total of 613 patients were randomized to Lurbinectedin + doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179).
Disease progression was the most common reason for stopping treatment (213 [770%] in the Lurbinectedin + doxorubicin group and 152 [53%] in the control group).

The median overall survival in the Lurbinectedin + doxorubicin group and the control group was 8.
6 months and 7.
6 months, respectively (HR 0.
97, p=0.
70).

Twelve patients died of treatment-related side effects: two in the Lurbinectedin + doxorubicin group and 10 in the control group
.
Patients in the lurbinectedin + doxorubicin and control groups experienced treatment-related side effects
in 98% (296/303 vs 284/289).
There were fewer hematologic side effects grade 3 or higher in the lurbinectedin + doxorubicin group than in the control group (19 versus 38 percent).

Overall, pre-controlled therapy combined with lurbinectedin combined with doxorubicin did not improve overall survival in patients with recurrent small cell lung cancer
.
However, the hematological safety of lurbinectedin combined with doxorubicin is superior to that of control
.

Original source:

Santiago Ponce Aix, et al.
Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial.
The Lancet Respiratory Medicine.
October 14, 2022.
https://doi.
org/10.
1016/S2213-2600(22)00309-5