Research in context
Evidence before this study
We searched PubMed for reports published since inception up to May 31, 2015, in any language using the terms “small cell lung cancer (SCLC)”, “chemotherapy”, “relapsed”, and “second-line”. Additionally, we examined abstracts from major international conferences of the same period (American Society of Clinical Oncology, European Society of Medical Oncology, and International Association for the Study of Lung Cancer annual meetings). We also searched clinical trial registers on ClinicalTrials.gov. With this search, we identified that after disease progression to first-line treatment, few therapeutic options are available for patients with SCLC, and that topotecan was the only drug approved during the past two decades for patients with disease sensitive to treatment. No approved therapies are accessible for patients with resistant disease (topotecan is approved for relapses at least 60 days after initiation of a platinum-containing first-line regimen). This search also showed that use of topotecan is challenging because of the associated haematological toxicity and the modest clinical benefit (overall response of around 16% was recorded in randomised clinical trials since 2014). In a phase 1 study in combination with doxorubicin, lurbinectedin showed remarkable activity in second-line SCLC; this finding led us to investigate lurbinectedin as a monotherapy in patients with SCLC.
Added value of this study
This study provides, to our knowledge, the first clinical evidence of anti-tumour activity for lurbinectedin as a single drug in patients with relapsed SCLC, with notable durable responses. Results detected by the investigators are robust and confirmed by an independent review committee. Our study also shows that lurbinectedin has an acceptable and manageable safety profile.
Implications of all the available evidence
Lurbinectedin appears to be a new valuable treatment option. The benefit observed with lurbinectedin compares favourably with that seen historically with topotecan, the current standard of care, in terms of both anti-tumour activity and safety. This drug profile is relevant for patients with relapsed SCLC, who are currently a population with a dismal prognosis.