KEY POINTS
- NRG-LU004 was a multicentre phase I study in unresectable or medically inoperable stage II–III NSCLC with PD-L1 TPS ≥50%, testing concurrent durvalumab and RT without concurrent chemotherapy.
- Durvalumab was given at 1500 mg every 4 weeks for up to 13 cycles, beginning approximately two weeks before RT. Patients received either accelerated RT (60 Gy in 15 fractions over 3 weeks) or standard RT (60 Gy in 30 fractions over 6 weeks).
- Among 24 evaluable patients, 12 per RT arm, the primary safety endpoint was met. No dose-limiting toxicity occurred with accelerated RT, while 1/12 patients in the standard-RT group experienced a DLT.
- Treatment-related toxicity remained substantial but manageable in this small cohort. In the accelerated arm, four patients experienced grade 3 events and one developed grade 4 lymphopenia; in the standard arm, eight patients had grade 3 events and no grade 4 events. Grade 5 events in each group were considered unrelated to protocol treatment.
- RT was delivered per protocol in 83% of evaluable patients. Early durvalumab feasibility was achieved in 85% of patients assigned accelerated RT and 75% receiving standard RT.
- Only 24% had completed all 13 planned durvalumab cycles at the time of analysis, while nearly half required some modification of durvalumab treatment.
- Exploratory longitudinal immune profiling identified treatment-related changes in circulating immune and soluble protein markers, including potential associations with adverse events, but these biomarker findings require independent validation.
CLINICAL TAKEAWAY
NRG-LU004 shows that concurrent durvalumab can be delivered with either conventional or accelerated thoracic RT in carefully selected PD-L1-high locally advanced NSCLC without concurrent chemotherapy. This is a safety signal, not evidence that chemotherapy can yet be omitted: only 24 patients were evaluable, and comparative disease-control or survival efficacy remains unknown.
SOURCE
International Journal of Radiation Oncology, Biology, Physics