An overview of studies on small cell lung cancer (SCLC) on lurbinectedin therapy was the focus of the presentations of the Spanish pharmaceutical company PharmaMar at the ASCO (American Society of Medical Oncology) Oncology Congress, which has just concluded in Chicago .
Of particular interest is the international LAGOON trial and a survey on patients over 65. Lurbinectedin is an inhibitor of oncogenic transcription, active in transcription-dependent tumours. A phase II basketball study in patients with small cell lung cancer (SCLC) treated with the molecule in second line showed an overall response rate (ORR) of 35.2% and a median duration of response (DoR) of 5 ,3 months, with durable responses (43.0% ≥ 6 months). Based on these findings, lurbinectedin already gained accelerated approval from the US FDA and in other countries, most recently including Switzerland. For definitive approval, the responses of the LAGOON trial are awaited, a phase III study involving 705 patients, with the participation of around twenty Italian centres, with the evaluation of two experimental arms (lurbinectedin alone or with irinotecan) compared Investigator’s Choice (topotecan or irinotecan) as a control arm in relapsed SCLC patients.
The other research centers involved range from the Institut Gustave Roussy in France to the Hospital Universitario 12 De Octubre in Madrid, from the CHUV University Hospital in Lausanne to the University of Manchester and the Dana-Farber Cancer Institute in Boston. The main inclusion criteria are: age equal to or greater than 18 years; confirmed diagnosis of SCLC; a prior line of platinum-containing chemotherapy with/without anti-PD-(L)1 and with a treatment-free period equal to or greater than one month. Patients with central nervous system metastases can participate if pretreated and radiologically stable for at least 4 weeks. An independent Data Monitoring Committee oversees the conduct of the study.
The final results, if positive, will lead to definitive approval in the USA so that they can also be presented to the European drug regulatory agency EMA.
The study on the over 65s, on the other hand, assumes that relapsed small cell lung cancer is a difficult disease to treat and a considerable number of patients are elderly with associated frailty and numerous comorbidities. This analysis specifically compares the study that led to US FDA accelerated approval of lurbinectedin every 3 weeks as second-line therapy in metastatic SCLC and the ATLANTIS study, which evaluated the lurbinectedin/doxorubicin combination as treatment second-line for SCLC versus a topotecan/CAV control arm. The result is that in elderly patients, lurbinectedin appears to be superior to standard of care both in terms of efficacy (higher response rate and longer duration of response and overall survival) and safety (fewer associated haematological adverse events), which strengthens the role as a therapeutic option in patients over 65 with recurrent SCLC. Finally, another study on small cell lung cancer concerns the ‘extended stage’ (ES-SCLC), i.e. aggressive and widespread in one or both lungs or in other areas of the body.
The study is in real-world and is part of the French Early Access Program (EAP-ATU), which involves 312 patients from various centers (64% male, average age 65). Lurbinectedin was administered second-line in 44% of patients (over half refractory to chemotherapy). The conclusions of the study highlight that lurbinectedin is an adjunctive second-line option for ES-SCLC, with efficacy results comparable to reference treatments and that real-world data confirm the efficacy and safety of the therapy.