Adding local consolidative therapy (LCT) after induction with nivolumab and ipilimumab does not improve survival in immunotherapy-naïve patients with metastatic non–small cell lung cancer (NSCLC), as shown in the phase III LONESTAR trial presented at WCLC 2026.
Overall survival (OS) favoured nivolumab-ipilimumab alone, according to study investigator Dr Mehmet Altan from the MD Anderson Cancer Center in Houston, Texas, US. At the June 15, 2026 cut-off, median OS was 52.8 months with nivolumab-ipilimumab alone vs 43.2 months with LCT + nivolumab-ipilimumab (HR, 1.14, 95 percent confidence interval [CI], 0.75-1.74; p=0.54). [WCLC 2026, abstract OA14.03]
Even among patients with oligometastatic disease receiving LCT after dual immunotherapy, OS did not improve at 90 weeks. OS trended worse with LCT-dual immunotherapy, with a median of 42 months vs 75.8 months with nivolumab-ipilimumab alone (HR 1.68, 95 percent CI, 0.87-3.26; p=0.12).
Additionally, the LCT-based strategy did not significantly improve progression-free survival (PFS), a coprimary endpoint. Median PFS was 31.3 months with LCT-dual immunotherapy vs 24.3 months with nivolumab-ipilimumab alone (HR, 0.79, 95 percent CI, 0.54-1.15; p=0.22).
In the oligometastatic cohort, median PFS was 35.7 and 44 months, respectively (HR, 1.38, 95 percent CI, 0.76-2.52; p=0.28).
Evidence does not support LCT after dual immunotherapy
During a press briefing, Altan said the LONESTAR regimen was feasible, but the findings “do not support the addition of routine LCT after nivolumab-ipilimumab induction for metastatic NSCLC without actionable genomic alteration (AGA) outside of a clinical trial.” The study was closed for futility after enrolling 166 patients.
The rationale for LCT is to eliminate residual or resistant clones at known disease sites after systemic therapy, thereby helping to delay progression and prolong survival.
“In metastatic NSCLC, incorporating LCT with targeted therapy or chemotherapy has improved PFS,” noted Altan. For example, in the NORTHSTAR trial of patients with EGFR-mutant locally advanced or metastatic disease, PFS was longer with osimertinib + LCT (25.4 months) than with osimertinib alone (17 months). [EClinicalMedicine 2025;87:103435]
In LONESTAR, investigators examined whether adding LCT (radiation or surgery) after dual immunotherapy could improve outcomes compared with dual immunotherapy alone in patients with EGFR-wild-type or ALK-negative metastatic NSCLC. After 12 weeks of nivolumab-ipilimumab induction, patients without progression or dose-limiting toxicity were randomized to continue nivolumab-ipilimumab alone (n=108) for up to 2 years or to LCT-dual immunotherapy (n=108). LCT included radiation to at least one disease site and surgery where feasible.
Of these patients, 77 had oligometastatic disease at randomization. Sixteen patients in the LCT-dual immunotherapy group underwent surgery, and 71 received at least one radiation session.
The median age was 66 years in the LCT-dual immunotherapy group and 67 years in the nivolumab-ipilimumab group. Other baseline characteristics, including sex, histology, smoking status, prior chemotherapy, palliative radiation, and PD-L1 expression, were balanced between the two groups.
In the subgroup analysis, only patients younger than 65 years showed an OS benefit with LCT-dual immunotherapy (HR, 0.43, 95 percent CI, 0.20-0.93).
The post hoc analysis demonstrated a link between mediastinal radiation and increased lymphopenia in the LCT group. According to Alta, this “may impair effector immune cells and blunt the benefit of consolidative therapy,” although LONESTAR was not powered to analyse this subgroup.
LCT-dual immunotherapy did not increase the overall incidence of grade ≥3 adverse events, but pneumonitis was more frequent with LCT-dual immunotherapy, affecting 9.5 percent of patients vs 4.9 percent in the nivolumab-ipilimumab only group.
According to Altan, an analysis by radiation site and type (intensity-modulated radiation therapy [RT] or stereotactic body RT as an LCT modality) is in progress.