Dr Faivre-Finn on Areas of Debate Surrounding Concurrent Chemoradiotherapy Plus IO in LS-SCLC

"There remain a number of questions with regard to patient selection. Of course, the 'Holy Grail' is the identification of a biomarker, and we do not have such a biomarker in the setting of SCLC."

Corinne Faivre-Finn, MD, a professor of thoracic radiation oncology at the University of Manchester and honorary consultant clinical oncologist at The Christie NHS Foundation Trust Manchester, discussed key areas of ongoing debate regarding concurrent chemoradiotherapy followed by immuno-oncology (IO) therapyin patients with limited-stage small cell lung cancer (LS-SCLC). Her discussion was based on a presentation delivered during the 2025 Global Bridging the Gaps in Lung Cancer consensus meeting.

A significant area of contention within the SCLC space is the selection of the appropriate radiotherapy treatment. Clinical trials have established that the standard of care includes twice-daily radiotherapy; however, this intensive regimen combined with chemotherapy is not feasible for all individuals, Faivre-Finn said. For example, patients with an ECOG performance status of 2 or higher may not be fit enough to receive this combination. Furthermore, logistical or practical issues related to the implementation of twice-daily treatments may exist in some treatment centers or for particular patients, Faivre-Finn noted.

Patient selection for immunotherapy represents another crucial debate, she continued, pointing to findings from the supporting the benefit of IO in this setting come primarily from the phase 3 ADRIATIC trial (NCT03703297), which supported the December 2024 FDA approval of durvalumab (Imfinzi) for the treatment of adults with LS-SCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. The selection criteria for this trial were stringent: only patients with an ECOG performance status of 0 or 1 were included. Moreover, the trial excluded individuals who experienced significant adverse effects related to their initial treatment or those with a history of autoimmune disease. These selection criteria leave a number of open questions concerning which patients beyond those fit subgroups should receive this treatment sequence.

Ultimately, the difficulty in optimizing treatment pathways stems from the absence of predictive tools. Faivre-Finn emphasized that although identifying a biomarker is considered the "Holy Grail" for guiding treatment decisions in LS-SCLC, such a biomarker is currently not available. Therefore, clinical decision-making must currently balance established efficacy standards (like twice-daily radiotherapy) against patient fitness and logistical feasibility, she concluded.