The recently concluded 2025 European Lung Cancer Congress (ELCC) spotlighted several key clinical topics and unveiled new research with strong translational potential. Oncology Frontier invited Professor Wei Zhang of Shanghai Chest Hospital, Shanghai Jiao Tong University for an in-depth interview, where she shared expert insights on the congress's most impactful themes and dissected the scientific highlights shaping the future of lung cancer treatment.Oncology Frontier：The FLAURA-2 and MARIPOSA studies led to the FDA’s approval in 2024 of new first-line combination treatment options for EGFR-mutant non-small cell lung cancer (NSCLC). Among the three available regimens—osimertinib monotherapy, osimertinib plus chemotherapy, and amivantamab plus lazertinib—how should clinicians determine the most suitable option for patients with advanced EGFR-mutant NSCLC?
Professor Wei Zhang:
Currently, for patients with EGFR-sensitive mutations in non-small cell lung cancer, all three treatment approaches—third-generation EGFR-TKI monotherapy, third-generation EGFR-TKI combined with chemotherapy, and the amivantamab-lazertinib combination—have received international regulatory approval. However, each regimen comes with its own advantages and drawbacks.
Osimertinib monotherapy offers a relatively shorter progression-free survival (PFS) but demonstrates a more favorable safety profile. When combined with chemotherapy, PFS improves; however, there have been ongoing questions about whether this combination confers a survival benefit in terms of overall survival (OS). At this year’s ELCC, the final OS results of the MARIPOSA study were released.
Findings from the MARIPOSA trial[¹] showed that the combination of amivantamab and lazertinib significantly improved OS with both statistical and clinical relevance (hazard ratio [HR]=0.75, P < 0.005). Median OS was not reached in the amivantamab-lazertinib arm, while it was 36.7 months in the control arm. Based on modeling estimates, this combination extended OS by an absolute value of 12 months compared with osimertinib monotherapy, with 36-month OS rates of 60% versus 51%, respectively.
It is worth noting that the amivantamab-lazertinib combination is currently not available in China. Moreover, safety concerns during combination therapy—such as lower limb edema and thromboembolic events—should not be overlooked and warrant close clinical attention.
Oncology Frontier：At the 2025 ELCC, French researchers presented findings from two expansion cohorts of the Phase I/II SOHO-01 trial. Could you comment on the safety and efficacy of BAY 2927088 in previously treated patients with HER2-mutant non-small cell lung cancer (NSCLC)?
Professor Wei Zhang:
HER2 mutations define a distinct subset of non-small cell lung cancer (NSCLC), accounting for approximately 2–4% of patients with advanced disease. Currently, two major therapeutic approaches are being explored in this setting: antibody-drug conjugates (ADCs), represented by DS-8201, and tyrosine kinase inhibitors (TKIs), such as BAY 2927088.
Previously, poziotinib was investigated in HER2-mutant NSCLC; however, it failed to gain approval due to limited objective response rates and considerable toxicity.
In the SOHO-01 study, BAY 2927088 demonstrated durable antitumor activity and a favorable safety profile in patients with HER2-mutant NSCLC, offering a promising new treatment option for this subgroup. According to updated data presented at this year’s ELCC[²], treatment-naïve patients achieved an objective response rate (ORR) of 70.5% and a disease control rate (DCR) of 81.8%. The median duration of response (DoR) was 8.7 months.
Oncology Frontier：What new data on ADC therapies in lung cancer were presented at the 2025 ELCC?
Professor Wei Zhang:
Antibody-drug conjugates (ADCs) are another major area of focus in lung cancer research. Since monoclonal antibodies can specifically target proteins expressed on the surface of tumor cells, ADCs theoretically offer greater specificity in drug delivery. However, across the current landscape of drug development, toxicity remains a widespread concern with ADCs—particularly bone marrow suppression. In addition, some ADCs have been associated with interstitial lung disease, posing challenges for both clinical application and future drug development.
Another hurdle lies in biomarker-driven patient selection. For several popular targets, such as Trop-2, B7-H3, and DLL3, no clear correlation has been established between expression levels and clinical efficacy, making it difficult to enrich the patient population most likely to benefit.
Going forward, the development of ADCs should focus on optimizing molecular design to reduce toxicity and refining dosing strategies to allow room for combination therapy in clinical settings.
Notably, several ADC-based combination strategies presented at this year’s ELCC hold promise for advancing clinical care. For example, the Phase II ORCHARD study investigated osimertinib in combination with Dato-DXd in patients with acquired resistance to EGFR-targeted therapies. Using a 6 mg/kg dose of Dato-DXd alongside osimertinib, the study reported an objective response rate (ORR) of 36%, with a median progression-free survival (PFS) of 11.7 months and a 12-month PFS rate of 39%. Grade ≥3 adverse events occurred in 56% of patients, suggesting meaningful antitumor activity despite notable toxicity.[³]
Oncology Frontier：One of the key topics discussed at the 2025 ELCC was whether immune checkpoint inhibitors should be excluded from treatment strategies for advanced non-small cell lung cancer (NSCLC) with oncogenic driver mutations. Could you share your insights on this?
Professor Wei Zhang:
The earlier view held that patients with oncogenic driver mutations should not receive immunotherapy, as it might lead to hyperprogression. However, with increasing clinical experience and ongoing research, this perspective has evolved. The prevailing consensus today is that for advanced NSCLC patients harboring driver mutations, targeted therapy should be prioritized as the first-line approach—except in cases of KRAS mutations.
That said, immunotherapy has increasingly found a role in patients who have developed resistance to targeted therapies. Studies such as ORIENT-31 and HARMONi-A have shown that combining immunotherapy with chemotherapy in this setting can offer survival benefits and has begun to reshape our clinical practice.
Oncology Frontier：The optimal duration of immunotherapy remains a matter of debate. In patients with advanced NSCLC, when should PD-(L)1 inhibitors be stopped, and is there a defined endpoint for treatment?
Professor Wei Zhang:
For patients with advanced NSCLC who are negative for driver mutations, the current standard duration for immunotherapy is two years. However, this two-year duration is not supported by strong evidence from randomized controlled trials. It is still unclear whether one year of treatment is non-inferior to two years, or whether continuing beyond two years provides additional benefit.
Therefore, the decision to stop treatment should be based on a comprehensive evaluation, taking into account the patient’s response to therapy, safety profile, and pharmacoeconomic considerations.
Oncology Frontier：Novel immunotherapies beyond PD-(L)1 inhibitors were a major focus in the educational sessions at ELCC. What are your thoughts on dual immunotherapy targets or bispecific immune checkpoint inhibitors, and do they carry a risk of excessive immune activation?
Professor Wei Zhang:
Currently, PD-1/PD-L1 inhibitors are the only immune checkpoint inhibitors approved for monotherapy use. While other promising targets—such as CTLA-4, LAG-3, and TIM-3—have been identified, none have been approved for use as monotherapies to date. The effectiveness of these new agents in combination likely depends on patient selection and biomarker-driven enrichment strategies.
Bispecific immunotherapies have become a hot topic in drug development. Commonly targeted combinations include PD-1/PD-L1 with CTLA-4, VEGF, or TGF-β. Some agents, such as PD-1/VEGF bispecific antibodies, have already been approved for use in China. As for the potential risk of overstimulating the immune system, this remains an open question that must be answered through rigorous clinical trials with objective data.
References:
- Yang JC, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line (1L) EGFR-mutant (EGFRm) Advanced NSCLC: Final Overall Survival (OS) from the Phase 3 MARIPOSA Study. European Lung Cancer Congress 2025, Abstract 4O.2.
- Girard N, et al. Phase I/II SOHO-01 Study of BAY 2927088 in Patients with Previously Treated HER2-mutant NSCLC: Safety and Efficacy Results from 2 Expansion Cohorts. European Lung Cancer Congress 2025, Abstract 3O.3.
- Le X, et al. Osimertinib (Osi) + Datopotamab Deruxtecan (Dato-DXd) in Patients (Pts) with EGFR-mutated (EGFRm) Advanced NSCLC (aNSCLC) Whose Disease Progressed on First-line (1L) Osi: ORCHARD. European Lung Cancer Congress 2025, Abstract 1O.
Professor Wei Zhang
Chief Physician, Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University
PhD, Doctoral Supervisor
Academic Affiliations:
- Standing Committee Member, Anti-Angiogenesis Targeted Therapy Committee, CSCO
- Standing Committee Member, Case Management Committee, Chinese Anti-Cancer Association (CACA)
- Member, Small Cell Lung Cancer Committee, CACA
- Member, Lung Cancer Group, Respiratory Medicine Branch, Shanghai Medical Association
- Member, Oncology Precision Medicine Committee, China Primary Health Care Foundation
- Member, Respiratory Medicine Committee, Chinese Research Hospital Association
- Youth Member, Respiratory Medicine Branch, Shanghai Medical Association
- Member, Lung Cancer Committee, Shanghai Women Physicians Association
- Member, Cancer Metastasis Committee, Chinese Medical Education Association
- Member, Expert Review Panel, Shanghai Science and Technology Commission
