Dr. Halmos on the Safety and Efficacy of Lurbinectedin in Second-line SCLC

Balazs Halmos, MD, professor, medical oncology, Department of Oncology, professor, oncology and hematology, Department of Medicine, chief, thoracic oncology, Albert Einstein College of Medicine, Montefiore Medical Center, discusses the safety and efficacy of lurbinectedin in the second-line setting for patients with small cell lung cancer (SCLC).

In June 2020, the FDA approved lurbinectedin for the treatment of adult patients with metastatic SCLC who experienced disease progression following platinum-based chemotherapy. In the second-line setting of SCLC, lurbinectedin has demonstrated some activity, and the agent has favorable tolerability compared with alternative approaches, Halmos says. Toxicities associated with lurbinectedin are primarily hematologic and gastrointestinal, and phlebitis is a key adverse effect to watch for in patients receiving the agent.

Although lurbinectedin monotherapy has demonstrated some efficacy and safety in the second-line setting, investigators are still examining ways the agent could be used in combination therapies. The phase 3 ATLANTIS trial (NCT02566993), which evaluated low-dose lurbinectedin plus doxorubicin vs physician’s choice of topotecan (Hycamtin) or cyclophosphamide/doxorubicin/vincristine, missed its primary end point when lurbinectedin plus doxorubicin failed to significantly improve overall survival (OS).

Data from the randomized ATLANTIS trial showed comparable OS between the two arms and a slight trend toward a progression-free survival benefit for lurbinectedin plus doxorubicin vs standard of care, Halmos notes. The outcome of this trial could be attributed to the use of a lower dose of lurbinectedin or the particular combination of lurbinectedin and doxorubicin, Halmos explains. However, additional studies are evaluating lurbinectedin in the first-line maintenance setting, and in combination with other agents, such as immunotherapy, in the second-line setting, Halmos adds.

Halmos also notes that some post-hoc analyses of the ATLANTIS trial have examined the outcomes of patients from the study who received lurbinectedin monotherapy after completing 10 cycles of lurbinectedin plus doxorubicin; however, he explains that these analyses have not been the most helpful for informing real-world decisions.

Although other combination trials with lurbinectedin are ongoing, single-agent treatment remains a viable second-line treatment in patients with SCLC. Rechallenging patients with platinum-based chemotherapy represents another option after this strategy demonstrated activity in a prospective phase 3 trial (NCT02738346) conducted in France, Halmos concludes.