The 2026 European Society for Medical Oncology (ESMO) Congress was held in Madrid, Spain, from October 23 to 27. Several major advances in lung cancer research were presented, covering cutting-edge areas such as maintenance therapy for small cell lung cancer (SCLC), precision treatment and perioperative management of non-small cell lung cancer (NSCLC), novel antibody-drug conjugates (ADCs), and immunotherapy-based combination strategies. Although the congress has concluded, academic interest in these findings continues. Oncology Frontier has therefore launched a special series to provide further insights into the key studies and developments presented at the meeting.This issue focuses on two Presidential Symposium studies, DeLLphi-305 (LBA3) and SAFFRON (LBA6). The former examines the efficacy and safety of first-line maintenance treatment for SCLC, while the latter explores the patient populations that benefit from treatment and the therapeutic positioning of the regimen in EGFR-mutated NSCLC with MET protein overexpression and/or amplification.
LBA3 — Efficacy and Safety of Tarlatamab Plus Durvalumab as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer: The DeLLphi-305 Study
This is a pivotal study evaluating the transition of tarlatamab from second-line treatment to maintenance therapy in extensive-stage small cell lung cancer (ES-SCLC). Median progression-free survival (PFS) was 1.9 months and 7.4 months in the two groups, respectively (HR=0.34, 95% CI 0.28–0.42), while median overall survival (OS) was 12.7 months and 21.1 months, respectively (HR=0.42, 95% CI 0.32–0.54). The incidence of grade ≥3 all-cause adverse events was 46.8% in the monotherapy group and 40.6% in the combination therapy group. Overall, the combination regimen substantially improved efficacy, with adverse events generally manageable.
Before the congress, Oncology Frontier published a preview commentary on this study, highlighting two key issues for consideration: first, the impact of the combination regimen on the incidence of cytokine release syndrome (CRS) and central nervous system adverse events; and second, whether the long-term tail of the survival curves would become more pronounced.
The results showed that the incidence of CRS was higher in the combination therapy group than in the monotherapy group, increasing from 1.4% to 49.6%, although most cases were grade 1–2. Grade 1–2 adverse events are generally considered to require relatively limited clinical intervention. However, it is important to note that even grade 2 events warrant close clinical attention when they involve the heart or central nervous system, or have the potential to lead to serious consequences. The most concerning complication of CRS is the induction of a cytokine storm, which may subsequently lead to systemic inflammatory response syndrome (SIRS). Further progression of SIRS can result in organ dysfunction, with the respiratory and urinary systems often affected at an early stage. Once such complications occur, clinical management can be challenging. Therefore, in evaluating CRS, attention should be paid not only to its incidence but also to the proportion of patients requiring additional interventions, including corticosteroids, tocilizumab, and mechanical ventilation. The investigators reported that 21.6%, 3.9%, 1.4%, and 0.4% of patients received corticosteroids, tocilizumab, additional oxygen therapy, and Venturi mask treatment, respectively.
Regarding the second point of interest, the survival curves showed a more pronounced tail in the combination therapy group. This suggests that adding tarlatamab may not only improve the short-term efficacy endpoint of PFS but also increase the proportion of patients achieving long-term remission or response. The two survival curves were clearly separated, with 12-month PFS rates of 9.5% and 38.4%, respectively. The presence of long-term responders is one of the important factors that may translate PFS benefits into OS benefits. At present, the median follow-up for the overall population is 15.9 months, and the follow-up period remains relatively limited. Longer follow-up will be needed to determine whether this long-term tail effect is sustained.
LBA6 — Efficacy and Safety of Osimertinib Plus Savolitinib Versus Platinum–Pemetrexed in Patients with Advanced EGFR-Mutated NSCLC Following Progression on Osimertinib and with MET Overexpression and/or Amplification
MET amplification is one of the important mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Based on the SACHI study, osimertinib plus savolitinib has been approved for this patient population. The present study not only provides further validation of previous findings but may also extend the population benefiting from this combination to include patients with MET protein overexpression, thereby providing evidence to define a broader treatment population.
In its pre-congress commentary on this study, Oncology Frontier highlighted two key questions: first, whether the combination regimen could be extended to patients with MET protein overexpression, particularly in terms of efficacy in this subgroup; and second, the positivity thresholds used to define the two patient populations. Recently, the study findings were also published in The New England Journal of Medicine.
In this study, MET protein overexpression was defined as MET staining intensity of 3+ in ≥90% of tumor cells by immunohistochemistry (IHC), while MET amplification was defined as a MET gene copy number ≥10 by fluorescence in situ hybridization (FISH). In terms of efficacy, median PFS in the overall population was 7.6 months in the dual-targeted therapy group and 5.4 months in the platinum-based doublet chemotherapy group (HR=0.55, P<0.001). Subgroup analyses showed that, among patients with MET protein overexpression, median PFS was 8.5 months and 5.6 months in the two groups, respectively (HR=0.51, P<0.001). Among patients with MET amplification, the corresponding median PFS was 7.6 months and 4.2 months (HR=0.48).
The MET protein overexpression subgroup deserves particular attention for the following reason: based on the SACHI study, patients with MET amplification can already benefit from osimertinib plus savolitinib. With the inclusion of patients with MET protein overexpression in the present study, it is important to determine whether the benefit observed in the overall population is driven primarily by the MET amplification subgroup and to clarify the independent contribution of the MET protein overexpression subgroup.
The SAFFRON subgroup analyses showed that patients in the overall population, the MET amplification subgroup, and the MET protein overexpression subgroup all benefited from combination treatment. These findings support extending the use of this combination regimen beyond patients with MET amplification to include those with MET protein overexpression, potentially establishing a broader population eligible for this treatment approach.
