2022 World Conference on Lung Cancer (ePosters)-EP14.03-003. Phase I Study of Palliative Radiotherapy with Lurbinectedin in Patients with Extensive Stage Small Cell Lung Cancer

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A phase I study was conducted to investigate the efficacy and safety of palliative radiotherapy (RT) combined with lurbinectedin in patients with extensive stage small cell lung cancer (ES-SCLC). Patients with relapsed ES-SCLC, who had progressed on platinum-etoposide, were administered lurbinectedin and evaluated for response rates, progression-free survival (PFS), overall survival (OS), and toxicities. Lurbinectedin demonstrated favorable activity, with an overall response rate (ORR) of 35.2%, 6-month PFS of 32.9%, and 6-month OS of 67.1%. The primary grade 3 toxicity observed was myelosuppression.<br /><br />Patients with ES-SCLC often require palliative RT to manage symptoms while receiving systemic therapy. Lurbinectedin was chosen for this study due to its ability to cause lethal single and double-strand DNA breaks, which plays a role in RT-induced lethality. However, the clinical experience of delivering palliative RT with concurrent or uninterrupted lurbinectedin was lacking.<br /><br />This investigator-initiated, open-label, non-randomized phase I study aimed to assess the safety and feasibility of delivering palliative RT to bone metastases or lung/visceral metastases with uninterrupted lurbinectedin in patients with ES-SCLC. The study included two safety cohorts, each consisting of 11 patients. Lurbinectedin was administered at a dose of 3.2 mg/m2 every 21 days, while RT was delivered to a maximum of 5 isocenters with a dose of 4 Gy x 5 or 3 Gy x 10, based on the discretion of the radiation oncologist.<br /><br />The primary endpoint of the study was safety events, including grade 4 or 5 serious adverse events related to treatment and any treatment-related adverse events leading to prolonged dose delays or permanent discontinuation of lurbinectedin. Secondary endpoints included feasibility, radiographic response rates, PFS, OS, pain response rates, and patient-reported outcomes. A tertiary/exploratory endpoint focused on hematologic toxicity rates according to irradiated bone marrow volume.<br /><br />The study, which is still ongoing, aims to determine the safety and feasibility of concurrent, uninterrupted RT with lurbinectedin. It is anticipated that concurrent RT and lurbinectedin administration will be safe, with an incidence of safety events of 15% in each safety cohort. The study will provide valuable insights into the combination therapy's efficacy and tolerability as a potential treatment option for patients with ES-SCLC.<br /><br />Research grant funding for the study was provided by Jazz Pharmaceuticals, and the participating sites include Emory University Hospital, Emory University Hospital Midtown, and Emory Saint Joseph's Hospital. The principal investigator of the study is Kristin Higgins, MD.

Asset Subtitle

Neal Sean Mccall

Meta Tag

Speaker Neal Sean Mccall

Topic Small Cell Lung Cancer and Neuro-endocrine Tumours - RT

Keywords

palliative radiotherapy

lurbinectedin

small cell lung cancer

efficacy

safety

response rates

progression-free survival

overall survival

toxicities

myelosuppression