Lurbinectedin Takes Center Stage in Second-line SCLC Treatment

Neil Morganstein, MD

Lurbinectedin (Zepzelca) OFFERS AN efficacious and well tolerated second-line option for patients with small cell lung cancer (SCLC), a population that is notoriously difficult to treat, according to Neil Morganstein, MD. Further research with the agent will include examining its use in novel combinations and evaluating its efficacy earlier in the treatment journey, he added.

The agent was approved by the FDA in June 2020 for use in adult patients with metastatic SCLC who progressed following platinum-based chemotherapy.¹ The regulatory decision was based on the results of a phase 2 basket trial (NCT02454972) that examined the efficacy of lurbinectedin in the second-line setting.2 A total of 105 patients were enrolled to the trial, and after a median follow-up of 17.1 months, investigators reported an overall response rate of 35.2% and a disease control rate of 68.6%. Serious treatment-related adverse effects were reported in only 10.5% of patients, with neutropenia (5%) and febrile neutropenia (5%) most commonly reported.

“Lurbinectedin is the first medication that has been approved for [patients with] recurrent SCLC cancer in many years. Since [the approval of] topotecan in 1998, there has been a vast dearth of treatment [options],” Morganstein said. “We [now] have a drug to replace topotecan: a new standard of care in the second-line setting that appears to be much better tolerated with a great and wonderful efficacy.”

In an interview with OncLive^® during an Institutional Perspectives in Cancer webinar on lung cancer, Morganstein, a medical oncologist at Atlantic Health System, discussed the impact of lurbinectedin on the SCLC treatment paradigm and future research directions with the agent in this population.

OncLive^®: Could you start off by speaking to the significance of lurbinectedin in SCLC? How does it differ from other agents, and how has the approval affected the paradigm?

Morganstein: Lurbinectedin is a unique molecule that was derived from the sea squirt [Ecteinascidia turbinata]. It intercalates into DNA and inhibits DNA synthesis. That allows it to be a well-tolerated medication in a setting that has been extraordinarily difficult to manage in the past.

[The fact that] a drug [finally] met the FDA’s requirements for approval is just tremendous, [after waiting so long]. We have used numerous medications in this field, but none of them have met the rigorous standards [for an] FDA approval. [We] finally have a drug [in the] National Comprehensive Cancer Network [NCCN] guidelines [that is] approved by the FDA; it just adds a new standard to the second-line treatment [paradigm for] metastatic SCLC.

What should be taken away from the results of the phase 3 ATLANTIS trial (NCT02566993)?

The ATLANTIS trial is somewhat curious. It was looking at lurbinectedin plus doxorubicin, and it did not meet its primary end point of overall survival. [However], the addition of doxorubicin is not [an approach that we] use in clinical practice. I suspect it was extrapolated from some earlier clinical trials that looked at a variety of different cancer types. The dose of lurbinectedin was also substantially lower in ATLANTIS [compared with what is often used]. It is really difficult to say what [should be made] of [these findings]. The FDA approval and the NCCN guidelines still strongly suggest the use of lurbinectedin in second-line SCLC.

Are any efforts further examining lurbinectedin in this disease?

One of the most [notable efforts] was a post hoc analysis [that looked at] incorporating immunotherapy, which is the most exciting treatment that we have [explored in oncology]. In the analysis, [investigators observed] very long survival in patients who received lurbinectedin and previously received immunotherapies. The next step is to explore combinations or [the] continuation of immunotherapies with lurbinectedin. Likely, this will be explored in the second-line setting and potentially [moved even] earlier [in the treatment journey].

Speaking of immunotherapy, what are your thoughts on the recent SCLC indication withdrawals by the FDA?

Although there have been some confusing results from clinical trials [with these agents] in SCLC, unless there is complete withdrawal of all agents, we are still enthusiastic about [them]. Clinical trial interpretation is challenging, and SCLC [represents] an extraordinarily difficult patient population. [These patients] do not do well, and [anyone who cares for them] knows that. [However], anyone who is sitting and speaking with a patient would rather have more agents to use and more opportunities to use them rather than fewer. Personally, I do not believe that immunotherapies are going away, and, to be honest, I hope they are not going away.

References

1. PharmaMar announces the US FDA approval of lurbinectedin (Zepzelca) for the treatment of metastatic small cell lung cancer. News release. PharmaMar. June 15, 2020. Accessed April 30, 2021. https://bit.ly/3hzSAAK
2. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654. doi:10.1016/S1470-2045(20)30068-1