Lurbinectedin-Doxorubicin Combo Misses Survival Mark in SCLC

A combination treatment for relapsed small-cell lung cancer (SCLC), involving the recently FDA-approved lurbinectedin (Zepzelca) plus doxorubicin, failed to improve overall survival (OS) versus standard chemotherapy, though it was certainly less toxic, according to the phase III ATLANTIS study presented at the virtual World Conference on Lung Cancer (WCLC).

Study author Luis Paz-Ares, MD, PhD, of Hospital Universitario 12 de Octubre in Madrid, explains why the combination failed and explains the next steps.

Following is a transcript of his remarks:

This is a very difficult disease. We have been doing a lot of trials over the last 2 decades, and one after the other has been really not positive. It is really difficult to impact on OS in the relapsing setting. We now know that this disease is very dynamic in the biologic evolution and is becoming really resistant, and resistant disease is really difficult to tackle therapeutically.

Anyway, we have seen some hints of activity. If we were to start the trial today, likely we wouldn't go with lurbinectedin/doxorubicin. So we are not sure about the addition of doxorubicin to this combo. We know that we are actually not able to give full doses of lurbinectedin, so in that sense, the activity of lurb alone is at least as good, and of course, the toxicity would be much better.

In terms of combinations, we are now trying a number of combinations. Particularly my group has been involved in two combos: One with irinotecan; the initial data are really promising; response rate 62%. PFS [progression-free survival] for those patients in the trial was actually longer with the second-line irinotecan plus lurb as compared to the first-line platinum/etoposide in that particular cohort of patients. And of course the combination with atezolizumab [Tecentriq], another PD-L1 inhibitor, is also very attractive. The drug itself is able to reshape the microbiome element to a more immunogenic one. And the initial data with PD-L1 inhibition in combination is really good, and those data will be released within the next few months in a coming meeting.

Comment