LAURA Trial, SINDAS Trial, NORTHSTAR Trial, and LONESTAR Trial
Panelists discuss how the LAURA trial demonstrated dramatic progression-free survival improvements with adjuvant osimertinib for EGFR-mutated stage III lung cancer, while the SINDAS, NORTHSTAR, and LONESTAR trials explore whether upfront local consolidative radiation therapy to oligometastatic sites can improve outcomes in both EGFR-mutated and nonmutated metastatic disease.
LAURA Trial, SINDAS Trial, NORTHSTAR Trial, and LONESTAR Trial
The LAURA trial addressed treatment for unresectable stage III EGFR-mutated non–small cell lung cancer, a population known to respond poorly to immunotherapy. Following chemoradiotherapy, patients were randomized to receive osimertinib or placebo. Results were striking, with a hazard ratio of 0.16 for progression-free survival (PFS)—osimertinib showed a median PFS of 39 months vs 5.6 months for placebo. This dramatic benefit suggests that without effective targeted systemic therapy, chemoradiotherapy alone provides inadequate disease control in this population. Central nervous system PFS was particularly impressive, with median not yet reached in the osimertinib arm vs 15 months in placebo, highlighting the drug’s ability to prevent brain metastases that commonly occur in EGFR-mutated disease.
Safety data from LAURA was reassuring despite concerns about pneumonitis risk when combining osimertinib with thoracic radiation. Grade 3 radiation pneumonitis occurred in only 2% of osimertinib patients vs 0% in placebo. All patients underwent brain MRI staging at enrollment, addressing concerns about inadequate staging. Subgroup analyses showed consistent benefit regardless of PET staging, with similar hazard ratios in PET-staged vs non–PET-staged patients. Overall survival data remains immature, with approximately 80% crossover to osimertinib in the placebo arm, which may complicate interpretation of final survival outcomes.
The SINDAS trial investigated oligometastatic EGFR-mutated disease, randomizing patients to tyrosine kinase inhibitor (TKI) plus radiation vs TKI alone, showing substantially better PFS and overall survival with upfront radiation. This phase 2 study, though not practice-changing, generated signals supporting earlier radiation intervention. The NORTHSTAR trial builds on these findings, testing both full and partial consolidation strategies in patients with oligometastatic and polymetastatic disease after initial TKI therapy. The LONESTAR trial applies similar principles to non–EGFR-mutated disease using immunotherapy, with results anticipated soon. These trials explore whether preventing disease seeding through strategic local therapy improves outcomes.
