Dr Igor Gómez-Randulfe Rodríguez examines four studies from WCLC 2026 that could influence the evolving management of small-cell lung cancer and molecularly defined non-small-cell lung cancer, from B7-H3 antibody-drug conjugates and MRI surveillance to emerging therapies targeting EGFR exon 20 insertions and ROS1.
“WCLC 2026 highlighted how rapidly treatment options are expanding across both SCLC and molecularly defined NSCLC… The challenge will be to understand how efficacy, CNS activity, durability and tolerability should inform treatment selection.”
The 2026 World Conference on Lung Cancer highlighted the increasing complexity of treatment selection across thoracic oncology, with several studies providing important new data in molecularly defined non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Here, Dr Igor Gómez-Randulfe Rodríguez (The Christie NHS Foundation Trust, UK) shares his perspective on four studies that particularly stood out, covering EGFR exon 20 insertion-positive NSCLC, prophylactic cranial irradiation (PCI), B7-H3-directed antibody-drug conjugates (ADCs) and ROS1-positive NSCLC.
Zipalertinib adds to the EGFR exon 20 treatment landscape
In EGFR exon 20 insertion-positive NSCLC, REZILIENT3 (NCT05973773) showed a significant progression-free survival (PFS) benefit with first-line zipalertinib plus platinum–pemetrexed chemotherapy. Median PFS was 14.5 versus 8.5 months with chemotherapy alone, corresponding to a hazard ratio (HR) of 0.50, while the objective response rate (ORR) was 65.0% versus 40.3%. This came with a greater toxicity burden, however, with grade 3 or higher adverse events occurring in 87.1% versus 54.4% of patients, driven predominantly by hematological events. Grade 3 or higher rash and diarrhoea occurred in 10.7% and 1.4% of patients, respectively, in the combination arm.
The results therefore need to be considered alongside the established first-line role of amivantamab plus carboplatin/pemetrexed following PAPILLON (NCT04538664). The final PAPILLON overall survival (OS) analysis reported median OS of 34.3 versus 27.9 months, although the difference was not statistically significant in the intention-to-treat analysis (HR 0.87; P=0.307). Importantly, 97 of 128 patients (76%) in the chemotherapy arm who discontinued because of disease progression subsequently received amivantamab, potentially attenuating the observed OS difference.
Zidesamtinib shows high activity in ROS1-positive NSCLC
The zidesamtinib data in ROS1-positive NSCLC were impressive, with a 94% ORR among 94 tyrosine kinase inhibitor (TKI)-naive patients. Central nervous system (CNS) activity was also notable: all 10 patients with measurable baseline brain metastases responded, with 70% achieving complete clearance of detectable intracranial disease. Responses appeared durable, with 86% of systemic responders remaining in response at 12 months. Median PFS had not been reached at the analysis, with 90% of TKI-naive patients remaining progression free at 12 months. Longer follow-up will be important, particularly because the treatment landscape already includes highly active next-generation ROS1 TKIs. Updated pooled TRUST-I (NCT04395677) and TRUST-II (TRUST-II) data for taletrectinib, for example, reported a median PFS of 46.1 months in TKI-naive patients after a median follow-up of 35.5 months. The challenge will therefore be to understand not simply whether new agents are active, but how efficacy, CNS activity, durability and tolerability should inform treatment selection.
MRI surveillance challenges the role of PCI in SCLC
The phase 3 SWOG S1827 (MAVERICK) trial (NCT04155034) was another highly relevant study, evaluating MRI surveillance with or without PCI in both limited-stage and extensive-stage SCLC. MRI surveillance alone significantly improved cognitive failure-free survival (CFFS), with an HR of 0.60, while preliminary OS data showed no apparent difference between the strategies. However, some caution is warranted before completely abandoning PCI. The study was initially designed with OS non-inferiority as its primary endpoint and an accrual target of 668 patients. Because of slow accrual, the protocol was amended so that CFFS became the primary endpoint. The trial ultimately randomised 304 patients, with the primary CFFS analysis involving 220 patients. For me, these results clearly shift the discussion towards MRI surveillance, particularly given the potential cognitive toxicity of PCI, but they do not completely close the question. The final OS analysis is still pending. The ongoing phase III PRIMALung trial (NCT04790253) will therefore be particularly important because it retains OS non-inferiority as its primary endpoint.
B7-H3 ADCs emerge as promising options in relapsed SCLC
There were also striking data with B7-H3-directed ADCs in relapsed SCLC. In TAISHAN-302, tambotatug pelitecan improved median OS to 13.3 versus 9.4 months compared with topotecan (HR 0.46), while median PFS was 7.4 versus 2.8 months. The objective response rate was 59.1% versus 9.7%. ARTEMIS-008 (NCT06498479) showed a similarly substantial benefit with risvutatug rezetecan. Median OS was 18.5 versus 10.3 months (HR 0.46), while median PFS was 7.2 versus 3.0 months. Both phase III studies were conducted in China, so validation across broader international populations will be important. Nevertheless, the consistency and magnitude of the efficacy signals suggest that B7-H3 ADCs could become an important therapeutic class in SCLC. Their eventual positioning alongside the T-cell engager tarlatamab will be particularly interesting. If T-cell engagers move further into earlier lines of treatment, B7-H3 ADCs could have an increasingly important role in subsequent-line therapy.
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: Expert perspectives from WCLC 2026: B7-H3 ADCs, MRI surveillance and emerging targeted therapies. touchONCOLOGY. 23rd September 2026.
Disclosure: Igor Gómez-Randulfe Rodríguez has no financial or non-financial conflicts of interest to declare in relation to this article.
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