New survival data and emerging treatment strategies are shaping the evolving lung cancer landscape. Dr Gabriel Lenz highlights five key trials from ESMO 2026, examining the latest findings and their potential implications for clinical practice.
“These results offer encouraging evidence of improved outcomes across several lung cancer settings, although the maturity of survival data, treatment-related toxicity and optimal treatment sequencing remain important considerations”
The European Society for Medical Oncology (ESMO) Congress 2026 brought important developments in lung cancer, with new data spanning maintenance treatment for extensive-stage small-cell lung cancer (ES-SCLC), targeted therapies for molecularly defined non-small-cell lung cancer (NSCLC) and antibody–drug conjugates (ADCs) in earlier and later treatment settings. Among the key findings were improved overall survival with maintenance tarlatamab plus durvalumab in DeLLphi-305, longer survival with divarasib in Krascendo 1 and promising results for sacituzumab tirumotecan in OptiTROP-Lung06 and OptiTROP-Lung04. SAFFRON also provided new evidence for biomarker-directed treatment following progression on osimertinib.
In this round-up, Dr Gabriel Lenz (AdventHealth, Orlando, FL, USA) reviews five key trials presented at ESMO 2026, highlighting the efficacy and safety findings, their potential clinical implications and the questions that remain.
Small-cell lung cancer
DeLLphi-305: Maintenance tarlatamab plus durvalumab in extensive-stage small-cell lung cancer
Abstract: LBA3 | ClinicalTrials.gov: NCT06211036 | Phase: III
The most talked-about lung cancer study, and one of the most important at ESMO 2026, was presented by Dr Jacob Sands. This phase III trial evaluated maintenance tarlatamab plus durvalumab versus durvalumab alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) without progression after first-line platinum–etoposide plus durvalumab (n = 563). Median overall survival (OS) was 21.1 vs 12.7 months (HR 0.42; p<0.001), and median progression-free survival (PFS) was 7.4 vs 1.9 months (HR 0.34). Confirmed objective response rate (ORR) was 26.4% vs 4.1%. Cytokine release syndrome (CRS) occurred in 49.6% vs 1.4%, mostly grade 1–2; grade ≥3 adverse events (AEs) occurred in 46.8% vs 40.6%.
Key clinical takeaway: DeLLphi is a practice-changing study. An OS HR of 0.42 is rarely seen in ES-SCLC, and these findings support the combination as a promising maintenance strategy for patients without disease progression following first-line chemoimmunotherapy.
Non-small-cell lung cancer
Krascendo 1: Divarasib versus other KRAS G12C inhibitors in advanced NSCLC
Abstract: LBA5 | ClinicalTrials.gov: NCT06497556 | Phase: III
Presented by Dr Ferdinandos Skoulidis, this phase III trial compared divarasib with sotorasib or adagrasib in previously treated, KRAS G12C inhibitor–naive, KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) (n = 338). With a median follow-up of 14.3 months, median PFS was 9.8 vs 5.7 months (HR 0.58; p<0.0001) and median OS was 17.7 vs 12.0 months (HR 0.56; p=0.0005). ORR was 58.4% vs 32.3%. Despite longer treatment duration, grade 3–4 treatment-related AEs were lower with divarasib (24.6% vs 34.5%), mainly low-grade GI toxicity, with no treatment-related deaths.
Key clinical takeaway: This is also a practice-changing result in the second-line setting. Divarasib beat an active KRAS G12C inhibitor on OS while having less high-grade toxicity, which is a strong combination. However, the control arm was almost all sotorasib, so superiority over adagrasib is less clear. The bigger question is whether KRAS G12C inhibition will move to first line in combination with immunotherapy.
SAFFRON: Osimertinib plus savolitinib following progression on osimertinib
Abstract: LBA6 | ClinicalTrials.gov: NCT05261399 | Phase: III
Presented by Dr Shun Lu, this phase III trial evaluated osimertinib plus savolitinib versus platinum–pemetrexed in EGFR-mutant NSCLC with centrally confirmed MET overexpression and/or amplification after progression on osimertinib (n = 338). Median PFS was 7.6 vs 5.4 months (HR 0.55; p<0.001), and OS was also improved at 53% maturity: 17.8 vs 12.9 months (HR 0.68; p=0.010). ORR was 51% vs 27%. Grade ≥3 treatment-related AEs occurred in 40% of patients in the osimertinib plus savolitinib arm and in 52% of patients in the platinum–pemetrexed arm with a similar incidence of serious TRAEs (14% versus 16%).
Key clinical takeaway: SAFFRON represents an important advance in the treatment of EGFR-mutant NSCLC following progression on osimertinib, particularly given the observed benefit in both PFS and OS. The findings support biomarker-driven treatment selection and reinforce the potential role of MET-targeted therapy in patients with MET alterations. However, the requirement for post-progression tissue assessment may limit its applicability in routine practice, and the optimal sequencing of savolitinib-based therapy relative to amivantamab-based regimens and antibody–drug conjugates remains to be established.
OptiTROP-Lung06: Sacituzumab tirumotecan plus pembrolizumab in first-line advanced NSCLC
Abstract: LBA66 | ClinicalTrials.gov: NCT06711900 | Phase: III
Presented by Dr Caicun Zhou, this phase III trial compared first-line sacituzumab tirumotecan (sac-TMT) plus pembrolizumab with chemotherapy plus pembrolizumab in untreated PD-L1–negative advanced nonsquamous NSCLC (n = 455). At a median follow-up of 9.7 months, median PFS was 15.0 vs 5.7 months (HR 0.49; p<0.001), with 12-month PFS of 51.1% vs 22.8%. ORR was similar (50.2% vs 47.3%), but responses were deeper and more durable (DoR 13.6 vs 6.8 months). OS was immature (descriptive HR 0.58). Grade ≥3 TEAEs were lower with sac-TMT (47.6% vs 60.6%); stomatitis was frequent but rarely grade 3.
Key clinical takeaway: More than doubling PFS against chemoimmunotherapy is impressive, and a chemotherapy-free first-line regimen for PD-L1–negative disease would be a major shift. However, OS is still immature and follow-up is short. Mature OS and global data are needed before it replaces the current standard.
OptiTROP-Lung04: Final overall survival results with sacituzumab tirumotecan
Abstract: LBA67 | ClinicalTrials.gov: NCT05870319 | Phase: III
Presented by Dr Wenfeng Fang, this phase III trial compared sacituzumab tirumotecan (sac-TMT) with platinum–pemetrexed in patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC following progression on EGFR-TKI therapy (n = 376). At a median follow-up of 32.3 months, mOS was 25.9 versus 17.4 months (HR 0.69; 95% CI 0.54–0.89; one-sided p=0.0021), with 24-month OS rates of 54.1% versus 37.2%. In a prespecified sensitivity analysis adjusting for subsequent ADC therapy in the control arm, the HR for death was 0.57 (95% CI 0.42–0.75). No new safety signals were identified with extended follow-up.
Key clinical takeaway: The final OS analysis strengthens the evidence supporting sac-TMT in this setting, demonstrating a clinically meaningful survival benefit over platinum-based chemotherapy.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (Claude.AI and ChatGPT 5.5). The content was developed and edited by human editors. No funding was received in the publication of this article.
Disclosure: Gabriel Lenz has no financial or non-financial conflicts of interest to declare in relation to this article.
Cite: ESMO 2026 lung cancer round-up: Five studies advancing the field. touchONCOLOGY. 28th October 2026.
Editor: Sophie Nickelson
