MD Anderson trial challenges local consolidative therapy paradigm in NSCLC

Adding local consolidative therapy (LCT) after induction treatment with nivolumab plus ipilimumab did not improve overall survival or progression-free survival in patients with metastatic non-small cell lung cancer (NSCLC), including those with oligometastatic disease, according to results presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).

Local consolidative therapy has improved outcomes in selected patients with oligometastatic NSCLC treated with chemotherapy, but its role in patients receiving immune checkpoint inhibitors has remained uncertain. The Phase III LONESTAR trial tested whether reducing residual tumor burden with radiation or surgery after dual immunotherapy could improve systemic disease control.

In this randomized trial, adding local consolidative therapy after induction dual checkpoint blockade was feasible, but it did not improve overall survival or progression-free survival in the overall population or among patients with oligometastatic disease."

Mehmet Altan, M.D., MD Anderson Cancer Center, Houston, Texas

LONESTAR was an open-label, single-center, randomized Phase III trial in immunotherapy-naive patients with metastatic NSCLC. After 12 weeks of induction nivolumab plus ipilimumab, patients without progression or dose-limiting toxicity were randomized to continue nivolumab/ipilimumab alone or receive LCT followed by nivolumab/ipilimumab. LCT consisted of radiation to at least one disease site, with surgery performed when feasible.

At the June 15, 2026 data cutoff, 166 patient were randomized: 83 to nivolumab/ipilimumab alone and 83 to LCT followed by nivolumab/ipilimumab. Seventy-seven patients had oligometastatic disease at randomization, and 16 patients in the LCT arm underwent surgery, 71 patients in the LCT arm received radiation to at least one disease site.

In the overall randomized population, median overall survival was 52.8 months with nivolumab/ipilimumab alone compared with 43.2 months with LCT plus nivolumab/ipilimumab (HR 1.14; 95% CI, 0.75-1.74; P=.54). Median progression-free survival was 24.3 months versus 31.3 months, respectively (HR 0.79; 95% CI, 0.54-1.15; P=.22).

Among patients with oligometastatic disease, median overall survival was 75.8 months with nivolumab/ipilimumab alone versus 42 months with LCT plus nivolumab/ipilimumab. Median progression-free survival was 44.0 months versus 35.7 months, respectively.

LCT did not increase the overall incidence of grade 3 or higher adverse events, although pneumonitis was numerically more frequent in the LCT arm, occurring in 9.5% of patients compared with 4.9% with nivolumab/ipilimumab alone. Investigators also observed markedly lower absolute lymphocyte counts when systemic therapy was restarted in the LCT arm.

The investigators concluded that adding LCT after induction dual checkpoint blockade was feasible but did not improve overall or progression-free survival in an unselected metastatic NSCLC population, including patients with oligometastatic disease.