From B7-H3-directed antibody-drug conjugates in relapsed small-cell lung cancer to emerging targeted therapies in molecularly defined NSCLC, Dr Federico Monaca (The Christie NHS Foundation Trust, UK) reflects on the WCLC 2026 data that could influence clinical practice – and the challenges that come with having more treatment options.
“More choice does not necessarily mean simpler treatment decisions. The challenge is no longer simply identifying effective treatments, but deciding how best to use them.”
The 2026 World Conference on Lung Cancer delivered several results with the potential to change clinical practice. My main takeaway was the speed at which effective options are multiplying in both small-cell lung cancer and molecularly defined non-small-cell lung cancer. The immediate advance is welcome, but it also makes treatment selection more complex: mature survival, intracranial control, toxicity, sequencing and access will increasingly matter as much as response rate or progression-free survival.
New second line options for small cell lung cancer
The most compelling data came from two remarkably concordant phase III trials of B7-H3-directed antibody-drug conjugates (ADCs) in relapsed small-cell lung cancer. In TAISHAN-302 (NCT06612151), tambotatug pelitecan improved median overall survival (OS) from 9.4 to 13.3 months compared with topotecan (HR 0.46), alongside a median progression-free survival (PFS) of 7.4 versus 2.8 months and an objective response rate of 59.1% versus 9.7%. ARTEMIS-008 (NCT06498479) produced an almost identical hazard ratio for OS with risvutatug rezetecan: median survival was 18.5 versus 10.3 months (HR 0.46), with median PFS of 7.2 versus 3.0 months and response rates of 58.3% versus 12.6%.
Both ADCs caused fewer grade 3 or higher treatment-related adverse events than topotecan, although myelosuppression remained common and pneumonitis deserves close attention, particularly with risvutatug rezetecan. These results are likely to establish B7-H3 ADCs as major second-line options and credible competitors to tarlatamab, without the practical burden of cytokine-release syndrome or ICANS monitoring. However, both studies were conducted only in China, quality-of-life data remain pending, and a reliable predictive biomarker has not emerged from B7-H3 immunohistochemistry. Global confirmation and rational sequencing with DLL3-directed T-cell engagers are therefore essential.
MRI surveillance and prophylactic cranial irradiation
The phase 3 phase III SWOG S1827 (MAVERICK) trial (NCT04155034) addressed a different but equally important question. Among 304 patients with limited- or extensive-stage small-cell lung cancer, MRI surveillance alone improved cognitive failure-free survival compared with MRI surveillance plus prophylactic cranial irradiation (HR 0.60). Preliminary OS was similar (HR 0.90), although the final analysis is pending. The findings support an MRI-led strategy for many patients, but they do not yet close the debate. OS remains the key safety endpoint, brain metastases were more frequent without PCI, and the intensive MRI schedule may be difficult to reproduce in health systems with limited capacity. The eventual decision should remain individualised and include cognition, intracranial control, quality of life and access to timely salvage treatment.
More choice in oncogene driven disease
For HER2-mutant NSCLC, DESTINY-Lung04 (NCT05048797) showed that first-line trastuzumab deruxtecan significantly prolonged median PFS versus platinum-pemetrexed and pembrolizumab (14.3 versus 8.3 months; HR 0.63), with response rates of 70.0% versus 44.5%. However, no OS advantage was evident at this immature analysis, subsequent treatments were imbalanced, and adjudicated interstitial lung disease or pneumonitis occurred in 20.8% of patients, including fatal events. With active oral HER2-selective TKIs such as zongertinib and sevabertinib also entering the first-line setting, convenience and pulmonary safety may influence treatment choice while mature survival and sequencing data are awaited.
EGFR exon 20 insertion-positive NSCLC is becoming similarly crowded. The PAPILLON (NCT04538664) update showed median OS of 34.3 months with first-line amivantamab plus chemotherapy versus 27.9 months with chemotherapy, but the difference was not statistically significant (HR 0.87), probably influenced by 76% on-protocol crossover. A prespecified crossover-adjusted analysis favored the combination (HR 0.57), although this remains model-dependent. REZILIENT3 (NCT05973773) added another option: zipalertinib plus chemotherapy improved median PFS from 8.5 to 14.5 months (HR 0.50) and response rate from 40.3% to 65.0%, including a favorable signal in patients with brain metastases. The price was substantially more grade 3 or higher toxicity, while OS remains immature. Cross-trial comparisons cannot define a winner; access, tolerability and the best sequence of antibodies and TKIs will be central.
In ROS1-positive NSCLC, the single-arm ARROS-1 study reported a 94% response rate with first-line zidesamtinib, with 90% of patients progression-free at 12 months. All 10 evaluable patients with CNS disease responded intracranially, and treatment discontinuation for toxicity was only 1%. These are exceptional early data, but longer follow-up and comparative evidence are needed before positioning zidesamtinib against established next-generation ROS1 inhibitors.
Immunotherapy continues to evolve
HARMONi-2 (NCT05499390) was another important signal. In a Chinese phase III trial of PD-L1-positive advanced NSCLC, first-line ivonescimab improved median OS versus pembrolizumab from 22.6 to 30.8 months (HR 0.73), building on the previously reported PFS benefit. The effect appeared greatest in PD-L1-high and squamous disease. These data challenge pembrolizumab monotherapy, but confirmation in a global population is needed before the result can be applied broadly.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. 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 (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: WCLC 2026: What the latest data mean for lung cancer treatment. touchONCOLOGY. 16th September 2026.
Disclosure: Federico Monaca has no financial or non-financial conflicts of interest to declare in relation to this article.
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