5 Updates From ESMO 2025 for Lung Cancer Oncologists
Key Points
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The MDT-Bridge trial showed that routine multidisciplinary assessment improved treatment outcomes for patients with non-small cell lung cancer (NSCLC).
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The FLAURA2 regimen of first-line osimertinib plus chemotherapy maintained survival benefit versus osimertinib alone in higher-risk subgroups of EGFR-mutated NSCLC.
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NorthStar data showed that additional local consolidation therapy improved survival in EGFR-mutated metastatic NSCLC.
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SOHO-01 and Beamion LUNG 1 reported positive findings for sevabertinib and zongertinib, respectively, in HER2-mutated NSCLC populations.
ESMO 2025 Lung Cancer Trials
On the Oncology Brothers podcast, Rami Manochakian, MD, of Mayo Clinic, joined Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, to discuss notable presentations in the NSCLC space at the European Society of Medical Oncology (ESMO) Congress 2025. The doctors reviewed data from the MDT-Bridge, FLAURA2, NorthStar, SOHO-01, and Beamion LUNG 1 trials.
MDT-Bridge Emphasizes Need for Multidisciplinary Assessment
The phase 2 MDT-Bridge trial enrolled patients with resectable or borderline resectable stage IIB to IIIB NSCLC to receive neoadjuvant durvalumab plus chemotherapy followed by either surgery or, in patients who became unresectable, chemoradiotherapy plus consolidation immunotherapy. The ESMO 2025 presentation covered the interim analysis of 84 patients with opportunity for 6 months of follow-up or completion of definitive surgery.
Based on a multidisciplinary baseline assessment, 56 patients were deemed resectable, while 28 were classified as having borderline resectable disease. After neoadjuvant durvalumab plus chemotherapy, 72 patients had surgery and 8 had chemoradiotherapy. The resection rate was 85.7% (95% CI, 76.4-92.4), and 68 of 72 surgical patients had no residual tumor. Of 76 patients deemed resectable by multidisciplinary reassessment after 2 cycles of neoadjuvant treatment, 60.5% achieved objective responses upon completing neoadjuvant treatment, with a pathological complete response rate of 27.6% (95% CI, 18.0-39.1).
“We know the jury is still out on neoadjuvant-only versus perioperative treatment, but what I like in this study is testing the concept of a multidisciplinary assessment throughout the process, a reminder for all of us to do better for our patients by making sure we’re always reassessing where they are in the treatment journey,” Dr. Manochakian said.
Updated Data From FLAURA2 Presented at ESMO
As was previously reported at the 2025 World Conference on Lung Cancer, the phase III FLAURA2 trial showed first-line treatment with osimertinib plus platinum-based chemotherapy improved overall survival (OS) versus osimertinib alone in patients with EGFR-mutated advanced NSCLC. The FLAURA2 data update presented at ESMO 2025 reported median OS outcomes for subgroups with poor baseline prognostic factors, including central nervous system (CNS) metastases, common EGFR mutations, detectable plasma EGFR mutation, and altered TP53.
Among patients with baseline CNS metastases, the median OS was 40.9 months (95% CI, 35.2-46.6) with osimertinib plus chemotherapy versus 29.7 months (95% CI, 25.6-35.8) with osimertinib alone (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99).
For common EGFR mutations, patients with the L858R mutation had a median OS of 38.1 months (95% CI, 33.4-42.0) with osimertinib plus chemotherapy versus 32.4 (95% CI, 28.0-37.6) with osimertinib (HR, 0.76; 95% CI, 0.55-1.07). In patients with an exon 19 deletion, median OS was not reached (95% CI, 47.2-not calculable [NC]) with osimertinib plus chemotherapy, and was 43.0 months (95% CI, 35.7-51.9) with osimertinib (HR, 0.76; 95% CI, 0.56-1.02).
In patients with detectable plasma EGFR mutation, the median OS was 38.4 months (95% CI, 33.2-46.6) with osimertinib plus chemotherapy versus 32.5 months (95% CI, 28.8-35.8) with osimertinib alone (HR, 0.79; 95% CI, 0.60-1.03). Lastly, in patients with altered TP53, the median OS was 51.1 months (95% CI, 35.0-NC) with osimertinib plus chemo versus 43.1 months (95% CI, 34.0-50.1) with osimertinib (HR, 0.71; 95% CI, 0.40-1.27).
“This is definitely a standard of care option that we owe to our patients to discuss… especially in these high-risk features,” said Dr. Manochakian.
NorthStar Results Support Local Therapy in Advanced NSCLC
In the phase II NorthStar study, physicians evaluated the addition of local consolidative therapy (LCT) to standard osimertinib care in EGFR-mutated metastatic NSCLC. The study enrolled patients who were either tyrosine kinase inhibitor (TKI)-naïve or who had acquired the T790M mutation without prior third-generation anti-EGFR TKI therapy.
A total of 119 patients were randomized to osimertinib alone (n=63) or osimertinib plus LCT (n=56). In the local consolidative therapy arm, the additional therapy was radiation in 59% of patients, surgery in 29%, and combined modalities in 12%. Any-grade adverse events occurred in over 96% of patients in each arm, and grade 3 adverse events occurred in 16% of patients in the osimertinib arm, compared to 29% in the osimertinib plus LCT arm. The primary endpoint, median progression-free survival (PFS), was 25.4 months with osimertinib plus LCT compared with 17.0 months with osimertinib alone (HR, 0.60; 95% CI, 0.40-0.92; P = .02).
Many oncologists already utilize upfront local consolidation therapy when treating EGFR-mutated NSCLC, Dr. Rahul Gosain said, and the NorthStar data further validates that approach for appropriate patients.
Sevabertinib in Treated and Untreated HER2-Mutated NSCLC
Sevabertinib is an oral, reversible TKI that has shown activity in HER2-mutated NSCLC models. At ESMO 2025, authors presented updated safety and efficacy data from the phase I/II SOHO-01 study on sevabertinib in advanced HER2-mutated NSCLC. The report described outcomes in patients with previous non-HER2 exon 21 insertion-targeted systemic therapy (cohort D), previous HER2-targeted antibody drug conjugate therapy (cohort E), and no prior systemic therapy for advanced disease (cohort F).
By the data cut-off, 81 patients in cohort D, 55 in cohort E, and 73 in cohort F had received sevabertinib. The objective response rate (ORR), median duration of response (DoR), 12-month DoR, and median PFS were reported as follows.
| Cohort D | Cohort E | Cohort F | |
| ORR | 64% (95% CI, 53-75) | 38% (95% CI, 25-52) | 71% (95% CI, 59-81) |
| Median DoR | 9.2 months (95% CI, 6.3-13.5) | 8.5 months (95% CI, 5.6-16.4) | 11.0 months (95% CI, 8.1-not evaluable) |
| 12-Month DoR | 42% (95% CI, 27-57) | 29% (95% CI, 5-53) | Not presented |
| Median PFS | 8.3 months (95% CI, 6.9-12.3) | 5.5 months (95% CI, 4.3-8.3) | Not reached |
The doctors agreed that sevabertinib will likely be approved for this population. They emphasized the absolute importance of next-generation sequencing testing in NSCLC to identify candidates for sevabertinib or other targeted therapies.
Beamion Lung 1: First-Line Zongertinib for HER2-Mutated NSCLC
Prior to ESMO 2025, the US FDA granted accelerated approval to zongertinib for patients with previously treated advanced HER2-mutated NSCLC based on phase Ib data from the Beamion LUNG 1 study. At ESMO 2025, authors presented first results for zongertinib in the treatment-naïve advanced HER2-mutated NSCLC cohort.
The treatment-naïve cohort included 74 patients with a median age of 67 years (range, 35-88). The cohort had an ORR of 77% (95% CI, 66-85), including 6 (8%) complete responses and 51 (69%) partial responses. An additional 14 (19%) patients achieved stable disease, providing an overall disease control rate of 96% (95% CI, 89-99). The 6-month DoR rate was 80% (95% CI, 65-89%), and the 6-month PFS rate was 79% (95% CI, 68-87%). Treatment-related adverse events occurred in 91% of patients, and grade 3 events occurred in 18%.
Given the positive results for zongertinib in Beamion Lung 1 and sevabertinib in SOHO-01, the optimal sequencing of therapies in HER2-mutated NSCLC will likely be an ongoing discussion, Dr. Manochakian said. While the data is still sparse, there are some signals that anti-HER2 agents could still have efficacy in sequence, similar to ALK-mutated disease, he added.