Adding LCT to Osimertinib Improves PFS Outcomes, Local Control Rates in EGFR-Mutated NSCLC

March 26, 2026 | Kyle Doherty

The addition of local consolidative therapy (LCT) to osimertinib (Tagrisso) significantly prolonged progression-free survival (PFS) compared with osimertinib monotherapy in patients with EGFR-mutated non–small cell lung cancer (NSCLC), according to findings from a secondary analysis of the phase 2 NorthStar trial (NCT03410043) presented during the 2026 European Lung Cancer Congress.¹ Moreover, consolidative radiotherapy led to excellent local control rates, with disease recurrence primarily occurring outside of the radiotherapy field at new distant metastatic sites.

Prior data from NorthStar presented during the 2025 ESMO Congress showed that patients who received LCT plus osimertinib (n = 56) achieved a median PFS of 25.3 months (95% CI, 19.4-45.0) compared with 17.5 months (95% CI, 14.5-24.4) among patients who received osimertinib monotherapy (n = 63; HR, 0.66; 95% CI, 0.50-0.87; 1-sided log-rank P = .025).²

Findings from the secondary analysis revealed that patients who received radiation BED therapy at a minimum dose of 75 Gy (n = 14) achieved a median PFS of 49.1 months (95% CI, 21.6-not estimable [NE]) vs 22.3 months (95% CI, 11.6-39.7) among those who received radiation BED therapy at less than 75 Gy (n = 16; HR, 0.31; 95% CI, 0.14-0.70; P = .006).¹

“[The] addition of LCT to osimertinib prolonged PFS [and] post-induction clearance of thoracic nodes, as well as pleural effusion, were potential predictors of benefit from LCT,” Saumil N. Gandhi, MD, PhD, an associate professor in the Department of Radiation Oncology, Division of Radiation Oncology, at The University of Texas MD Anderson Cancer Center in Houston, said during the presentation.

How was the secondary analysis of NorthStar designed?

NorthStar was a randomized, multicenter trial that enrolled patients with locally advanced or metastatic NSCLC.² Other key enrollment criteria included having an ECOG performance status of 0 or 1, measurable disease, and TKI-naive EGFR exon 19 deleted or L858R-mutated disease or acquired T790-mutated disease without receiving a prior third-generation TKI.

Patients were randomly assigned 1:1 to receive osimertinib or osimertinib plus LCT; both arms received 6 to 12 weeks of osimertinib induction therapy. The primary end point was PFS. Key secondary end points included safety, overall survival, PFS in patients with at least 3 metastatic sites, and PFS in TKI-naive patients.

The real-world, secondary analysis of NorthStar sought to elucidate how safe and effective radiation therapy can be delivered in this patient population; which patients derive the greatest benefit from LCT after induction osimertinib; and where patients fail following LCT.

At baseline, patients included in the secondary analysis had oligometastatic (n = 35) or polymetastatic (n = 84) disease. After induction therapy, patients had oligometastatic (n = 35), induced oligometastatic (n = 15), or polymetastatic (n = 69) disease. Fifty-six patients were randomly assigned to receive LCT; 100%, 71%, and 56% of patients with oligometastatic, induced oligometastatic, or polymetastatic disease, respectively, completed LCT.

What other data were shared from the secondary analysis?

Assessment of potential predictors of benefit with this approach revealed that nodal clearance following induction osimertinib was associated with improved outcomes after osimertinib plus radiation therapy. Specifically, patients with present nodes (n = 18) achieved a median PFS of 22.3 months (95% CI, 11.6-27.9) compared with 49.1 months (95% CI, 21.6-NE) among those with absent nodes (n = 12; HR, 0.34; 90% CI, 0.15-0.76; P = .011). Patients with thoracic nodes present at random assignment who received osimertinib plus LCT (n = 34) and osimertinib monotherapy (n = 34) experienced a median PFS of 19.0 months (95% CI, 12.6-23.2) and 15.9 months (95% CI, 10.9-23.9), respectively (HR, 0.93; 90% CI, 0.60-1.43; P = .388). Patients in the combination (n = 22) and monotherapy (n = 28) arms who had absent thoracic nodes at random assignment had a median PFS of 41.5 months (95% CI, 31.2-NE) and 19.6 months (95% CI, 9.1-31.5), respectively (HR, 0.43; 95% CI, 0.23-0.78; P = .008).

Pleural effusion clearance after induction osimertinib was also found to be predictive of a benefit with LCT. Patients in the combination (n = 17) and monotherapy (n = 26) arms who had a pleural effusion present at random assignment experienced a median PFS of 15.3 months (95% CI, 11.6-23.9) and 12.9 months (95% CI, 8.5-20.9), respectively (HR, 0.90; 90% CI, 0.52-1.55; P = .373). Comparatively, the median PFS values were 32.7 months (95% CI, 19.7-48.2) and 22.3 months (95% CI, 14.5-28.1) in the combination (n = 37) and monotherapy (n = 36) among patients who did not have a pleural effusion at random assignment (HR, 0.63; 90% CI, 0.39-1.02; P = .057).

“We [also] found that that [approximately] 20% of patients had local, regional-only recurrence as their first site of recurrence, but the recurrences were predominantly distant, as one might expect,” Gandhi added. “In fact, when these recurrences happen, they tended to happen at new sites that were never involved at baseline or at presentation in the patients [who] received radiation. Radiation provided excellent local control [rates] over 90% with the vast majority of patients failing outside the prior radiation field, and the most common sites of recurrences were [the] lung, bone, and the central nervous system.”

In terms of safety, patients in the radiation cohort experienced grade 1 pneumonitis (2.3%), esophagitis (7.1%), and dyspnea (28.5%), These events occurred at grade 2 severity at respective rates of 11.9%, 2.3%, and 2.3%. Grade 3 pneumonitis was reported in 2.3% of patients.

Disclosures: Gandhi received research support from and serves on the scientific advisory board for Johnson & Johnson. He also received research grants from Nanobiotix Inc, Takeda Pharmaceuticals, and AstraZeneca.

References

Gandhi SN, Chang E, Antonoff MB, et al. Predictors of benefit from local consolidative therapy and patterns of failure for metastatic EGFR-mutant NSCLC: a secondary analysis of NorthStar, a randomized phase II clinical trial. Presented at: 2026 European Lung Cancer Congress; March 25-28, 2026; Copenhagen, Denmark. Abstract LBA3.

Elamin YY, Gandhi S, Antonoff M, et al. NorthStar: a phase II randomized study of osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Ann Oncol. 2025;36(suppl 2):S1614. doi:10.1016/j.annonc.2025.09.086