Nature Medicine, Published online: 17 April 2026; doi:10.1038/s41591-026-04404-8
Publisher Correction: Reliability of LLMs as medical assistants for the general public: a randomized preregistered study
RSV Vaccination in Late Pregnancy Reduces Infant Hospitalizations
Results from a large U.K. study show that vaccination against respiratory syncytial virus (RSV) at least two weeks before giving birth has a significant protective effect against hospitalization for this infection in babies born to these mothers.
As reported at the congress of the European Society of Clinical Microbiology and Infectious Diseases in Munich this week, the researchers found that vaccination reduced a baby’s risk of being admitted to hospital with serious RSV lung infections in the first months of life by around 80% versus no vaccination.
Notably, the benefit from vaccination increased if mothers were vaccinated at least four weeks before the baby was born, although even if they received the vaccine 10-13 days before delivery the risk of hospitalization for their babies in subsequent months still went down by 50%.
“As the largest study to date examining the impact of this vaccine on infant hospitalization, these findings provide robust evidence that vaccination offers substantial protection against severe illness in young infants,” commented lead author and UK Health Security Agency epidemiologist Matt Wilson in a press statement.
“We found a clear relationship between timing and protection, with effectiveness increasing as the interval between vaccination and birth lengthens, reaching close to 85% when vaccination occurs at least four weeks before delivery.”
After a national RSV vaccination campaign for pregnant women began in the U.K. in September 2024, around 55% coverage was reached by December of the same year. In total, 289,399 infants born between September 2024 and March 2025 were included in the cohort of which around 55% were vaccinated via maternal exposure. Vaccination was considered ‘full’ if mothers received it at least 14 days before giving birth.
The team followed up the babies for around three months after birth to monitor for RSV-associated lower respiratory tract infections requiring hospitalization, which affected a total of 4,594 babies.
Overall, unvaccinated babies had around seven times the rate of RSV‑related hospital admissions compared with babies whose mothers were vaccinated during pregnancy. Preterm infants also benefitted significantly from the vaccine.
“These findings are particularly important for preterm infants, who are among the most vulnerable to severe RSV infection,” said Wilson. “With sufficient time between vaccination and birth, we saw good levels of protection in these babies. Giving the vaccination early in the third trimester, as recommended by the World Health Organization, could protect most preterm infants.”
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Preliminary Usability Assessment of a Rule-Based Digital Self-Monitoring Platform for Patients With Brain Tumors Toward Digital Early Warning Systems: Pilot Feasibility Study
<strong>Background:</strong> Postoperative follow-up after brain tumor surgery is typically limited to intermittent clinic visits, leaving subtle neurological or general deterioration between visits underrecognized. Digital self-monitoring platforms may help fill this gap, but evidence in neuro-oncology is scarce, particularly regarding how patient-reported symptom trajectories can feed into future data-driven early warning systems. <strong>Objective:</strong> This study aimed to evaluate the feasibility, use patterns, and preliminary usability of a smartphone or web-based self-monitoring system for patients after brain tumor surgery and to explore simple rule-based digital alerts as a first step toward an advanced digital early warning framework. <strong>Methods:</strong> We conducted a single-center prospective pilot study including adults discharged after brain tumor surgery who had access to a smartphone and could use a web app. Participants completed brief symptom surveys consisting of 51 binary items across 7 symptom domains, with an automatically calculated daily total score and score history visualization. Feasibility was assessed by enrollment, retention, submission counts, and submission rates. A total of 4 interpretable alert rules based on current score, short-term worsening, new-onset symptom combinations, and persistence across domains were evaluated using each patient’s last 3 submissions as the analytic unit. Clinical deterioration was defined a priori as objective decline in performance status, new neurological deficit, radiologic progression, or clinically significant laboratory changes. Rule performance metrics and bootstrap CIs were computed. Usability and acceptability were evaluated using the System Usability Scale and additional adherence-related items. <strong>Results:</strong> Of 64 enrolled patients, 30 (47%) with ≥3 submissions formed the analysis cohort (median age 57, IQR 47.2–64.5 years; n=12.9, 43% malignant tumors); 6 (20%) experienced clinical deterioration during follow-up. Patients contributed a median of 8.5 submissions (mean 19.03, SD 30.12) at 1.7 surveys per week on average, indicating sustained but heterogeneous engagement. The best-performing rule, based on net short-term score increase, achieved an area under the receiver operating characteristic of 0.88, with sensitivity 0.83, specificity 0.92, and accuracy 0.90 on the last-window dataset, outperforming rules based solely on current score or multidomain persistence. Among 23 app users who completed the System Usability Scale, the mean score was 84.0, reflecting high perceived usability; higher-frequency users reported stronger perceived usefulness and habit-driven use. <strong>Conclusions:</strong> This pilot study demonstrates that a smartphone or web-based self-monitoring platform for patients with brain tumor is feasible and well accepted and that simple, transparent rules applied to longitudinal symptom scores show potential to capture early signals of clinical deterioration. However, given the small sample size, these predictive metrics are preliminary and require rigorous validation in larger, independent cohorts. These findings support further development of integrated digital early warning systems that combine patient-reported trajectories with clinical and physiological data to enhance postoperative neurosurgical care.
Tunneling Neurons in Adult Bird Brains Provide New Insights into Neurogenesis
Despite its small size—it could sit in the palm of your hand—the zebra finch is a remarkable learner. A songbird native to Australia, it’s renowned for its ability to pick up new songs. That talent has made it a favorite of scientists studying how animal brains imprint new skills, particularly vocal learning, or the capacity to perfect new sounds.
Researchers at Boston University, working with scientists at the Max Planck Institute for Biological Intelligence and the MRC Laboratory of Molecular Biology, have now discovered another quirk to the zebra finch brain—one that could also have implications for understanding our own. In a study that looked at the bird’s brain in unprecedented detail, the scientists uncovered new insights into neurogenesis—the birth, migration, and maturation of neurons—that may help the brain learn, add new skills, and restore and repair itself.
Observing the finch brain using a high-powered microscope, the researchers watched as new neurons made their way through the brain en route to bolstering existing circuits and connections. The expectation was that these neurons would step around established brain structures, including more mature brain cells, to better preserve them. Instead, the investigators saw the neurons tunnel right through. According to the BU-led team, the findings could help explain human vulnerability to a range of brain disorders. The researchers also noted that cell tunneling is used by some metastatic cancer cells.
“We found that in songbirds, new neurons in the adult brain behave like explorers forging a path through a dense jungle,” said Benjamin Scott, PhD, a BU College of Arts & Sciences assistant professor of psychological and brain sciences and the study’s corresponding author. That may help them learn new things or repair damage, but it could come with a cost to existing cells and memories—and that might be why neurogenesis is, in humans, something that doesn’t seem to extend beyond the womb. “This potentially disruptive behavior may help explain why humans and other mammals have limited capacity to regenerate brain tissue in adulthood,” commented Scott, “leaving us more vulnerable to neurodegenerative disorders such as Alzheimer’s disease.”
Scott is senior and corresponding author of the team’s published paper in Current Biology, titled “Songbird connectome reveals tunneling of migratory neurons in the adult striatum,” in which the researchers commented that their collective findings “… suggest that migrating neurons may physically reshape the mature circuit to reach their targets, revealing an unexpected degree of structural and functional plasticity in the adult brain.”
At birth our brains have pretty much all the neurons they are ever going to have. Other organs—from your skin to your heart—might get frequent cell updates, but the brain is working on version 1.0. That’s true for most mammals, but not for fish, reptiles, and birds—their brains get a regular refresh.
“This raises two questions,” said Scott, who’s also affiliated with BU’s centers for neurophotonics, photonics, and systems neuroscience. “Why do other species have high rates of neurogenesis throughout life and why is it so restricted in humans? And is there something we can learn from their biology that we might be able to harness in future?”
Scott typically studies the neural circuits that control behavior in humans and other mammals, but chose the zebra finch to investigate neurogenesis because it has a reputation as a champion species—it’s really good at generating new neurons. “Songbirds are valuable model organisms for the study of neuron migration in the adult brain,” the authors wrote. “In these species, new neurons integrate into brain regions that control complex learned behaviors, where they establish synapses with mature neurons and respond to sensory stimuli.”
However, the team pointed out, a key question is how these new neurons interact with mature circuit structures in the brain. “It is not known whether neurons pursue migratory routes that flexibly avoid these structural obstacles or deform surrounding tissue to reach their targets,” they wrote. “While prior studies have examined the molecular mechanisms and functional consequences of adult neurogenesis, few have investigated the physical interactions between migrating neurons and their surrounding microenvironment.”
For their newly reported study the team used electron microscopy (EM)-based connectomics to examine how migrating neurons interact with mature circuit elements. “We applied a new tool to study this process [neurogenesis] called electron microscopy-based connectomics—basically a really high-powered microscope—to image these cells at a very high resolution,” Scott explained. “Our first hope was just to say, what does this look like at a detail we couldn’t see before?”
Their resulting data revealed intricate interactions between migratory neurons in the adult striatum and their environment, but also showed up the tunneling neurons. “Our findings support a model in which migrating neurons disperse throughout dense neural tissue in multiple directions, making various contacts with surrounding structures,” the team wrote in summary. “In addition, our data reveal a previously undescribed form of neuron migration in which new neurons cause deformities in nearby neurons and synapses.”
The authors say that, to their knowledge, tunneling migration by neurons hasn’t previously been reported in the vertebrate nervous system. It’s possible that this is due to the constraints of study methods used, but it’s also possible that tunneling is a specialization of neurogenesis in birds.
If these new neurons are deforming brain tissue, commented Scott, are they also disrupting memories along the way? And, if neurogenesis comes with a cost, how does that balance against the brain’s capacity for learning new things and repairing after injury? And as the authors pointed out, “Interestingly, tunneling-like behavior has been described in metastatic cancer cells, which navigate confined spaces by actively deforming their microenvironments. Tunneling may therefore reflect a conserved strategy adopted by specialized migratory cell types in dense tissues.”
Scott has two—as yet untested—hypotheses for what the findings might mean for the human brain. The first is that our brains evolved to limit neurogenesis after birth as a form of protection—a way of making sure determined neurons couldn’t barge through mature connections and damage memory storage. “There is an alternative framing that is more optimistic,” he also noted. “Our discovery of tunneling shows how cells can move without glia scaffolds.”
These are the structures that operate as highways for migrating neurons. “Most glia scaffolds are lost in humans after birth, and this loss was thought to be an obstacle for neurogenesis in the adult brain,” says Scott. “However, our work shows that new neurons in the bird do not need this glia scaffold. This is exciting because it means that brain repair may not require specialized glia scaffolds.” That opens the door for scientists to explore potential stem-cell therapies that would spark neurogenesis in humans.
In summary, the authors wrote, “These results reveal the value of applying EM connectomics to adult neurogenesis and suggest that migratory neurons may dramatically perturb the existing functional circuits as they migrate and integrate. Furthermore, they reveal the remarkable structural flexibility of mature neural circuits.”
In current studies, Scott and the team in his BU Laboratory of Comparative Cognition are digging into the biology driving neurogenesis to uncover which genes are regulating the process. Much of the work merges ideas and tools from biomedical engineering and neuroethology, the study of the mechanisms underpinning animal behavior.
“Right now, we’re using a technique called single-cell RNA sequencing to identify genes that are expressed by these new neurons as they migrate,” said Scott. “We want to know what other cells they’re talking to as they move and how they are speaking to these different cells.” That’ll help them figure out whether neurons warn other cells they’re traveling through and how they know where to stop and integrate with a current circuit.
“We share a lot with our animal relatives on this planet,” noted Scott. And, while the term “bird brain” might be an insult, by learning more about the biology of songbird brains, he says, we could learn some remarkable things about our own.
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Use of Wearable Devices to Augment Traditional Measurements of Postoperative Outcomes Following Total Joint Arthroplasty: Systematic Review
Background: Wearable devices enabling remote monitoring by surgeons of their patients have gained prominence around total joint arthroplasty (TJA), offering continuous patient data to identify those not meeting postoperative goals, thereby facilitating timely interventions. While multiple studies highlight the utility of these devices in tracking postoperative progress, a standardized approach to their application is lacking. This review aims to synthesize existing literature on the use of wearable device-tracked activity for monitoring TJA outcomes. Objective: We examined the current literature to evaluate how wearable devices are used in monitoring and improving patient rehabilitation and outcomes following TJA. Methods: A systematic review was conducted following Cochrane methodology. A literature search of all available literature was performed in April 2024 and identified 102 studies to undergo full-text review. Systematic reviews, duplicate papers, and theoretical papers were excluded. Ultimately, 35 studies met the selection criteria. Results: The review revealed that 32 of 35 (91.4%) studies used wearable devices to monitor step counts. A total of 21 (60%) studies incorporated joint-specific patient-reported outcome measures, though the specific measures varied. Further, 9 studies used standardized performance-based outcome measures, which also differed across studies. Finally, 7 (20%) studies collected sleep data; however, the methods and outcomes for sleep measurement were inconsistent among these studies. Conclusions: Remote monitoring via wearable devices offers a novel approach to tracking outcomes in TJA patients. Although the use of these devices in perioperative care is expanding, significant variability exists in the data reported across studies. Wearable monitoring is often integrated with patient-reported outcome measures and standardized functional assessments, yet the optimal data parameters that best correlate with established outcome metrics remain undefined. Additionally, data collected by wearables has not yet been shown to predict patient recovery or satisfaction. Further research is essential to refine these data parameters and the development of postoperative protocols that leverage wearable devices to enhance patient compliance and improve clinical outcomes. Trial Registration: PROSPERO CRD420261346230; https://www.crd.york.ac.uk/PROSPERO/view/CRD420261346230
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Impact of Prescribed and Self-Selected Music Interventions on Stress, Sleep, Heart Rate Variability, and Brain Connectivity in Surgeons Using 7-Tesla Functional Magnetic Resonance Imaging and Wearable Actigraphy: Multimodal Feasibility Randomized Controlled Trial
<strong>Background:</strong> Stress, sleep deprivation, and burnout are significant safety risks for acute care surgeons, negatively impacting performance, well-being, and clinical outcomes. <strong>Objective:</strong> This pilot randomized controlled trial aimed to measure neurophysiological effects of prescribed music (PM) and self-selected music (SSM) on surgeon stress, burnout, and neurophysiological responses using a multimodal protocol that integrated functional magnetic resonance imaging (fMRI), wearable biosensor monitoring, and psychological self-assessments. <strong>Methods:</strong> Full-time attending surgeons at a quaternary care hospital were invited to participate in a 3-armed trial (1:1:1 block allocation). Intervention groups were instructed to listen to 30 minutes (minimum 15 minutes) of either PM or SSM daily at bedtime for 6 weeks, reflecting real-world conditions. PM comprised original compositions based on elements promoting perceived relaxation from a prior study. The control arm avoided music in the 30 minutes before bed. Allocation was concealed from the recruiting investigator; the fMRI technicians, the statistician, and lead investigators were blinded until analyses were completed. Functional connectivity patterns were measured using fMRI at baseline and 6 weeks while participants listened to simulated intensive care unit noise, PM, and SSM. Secondary outcomes included continuous actigraphy for sleep quality and self-reported anxiety, sleep quality, and burnout using validated scales (State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, and Maslach Burnout Inventory). <strong>Results:</strong> A total of 22 surgeons were assessed; demands of fMRI and data collection schedule led 3 to decline and 2 (allocated to PM) not to finish baseline measures; 6 PM, 5 SSM, and 6 controls received allocated intervention; 2 PM participants were withdrawn for nonadherence and missing follow-up data and 1 control missed follow-up collection due to scheduling (final analysis set after missing data: PM: n=4, SSM: n=5, control: n=5). One control participant experienced transient vertigo in fMRI. Trends in fMRI data indicated that both intervention groups experienced less negative emotional arousal and anxiety, with physical tension reduced in the PM group. The PM group exhibited reduced stress response in the frontal lobes when exposed to intensive care unit alarms, suggesting diminished attentional response to the high-stress auditory environment, compared to control. However, lack of statistical significance and baseline variability entail cautious interpretation. Observations of sleep quality were mixed, and no statistically significant differences in stress surveys were observed. <strong>Conclusions:</strong> Both music interventions trended toward positive changes in neurophysiological responses, suggesting potential benefits in reducing surgeon stress. However, due to the small sample, mixed or nonsignificant results, and the exploratory nature of this study, findings should be considered preliminary. Further research with larger, diverse cohorts is required to confirm trends, refine both the intervention approach and recruitment strategies, and determine whether objective compositional elements or personally selected music drive the mechanisms of potential positive effects. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT05980429; https://clinicaltrials.gov/study/NCT05980429
Involving Health Care Professionals in the Human-Centered Design of a Digital Platform for Work-Focused Health Care: Lessons From a Mixed Methods Study
<strong>Background:</strong> Effective collaboration throughout the full cycle of care is essential for value-based health care. In the Netherlands, occupational health care and curative health care traditionally operate as 2 separate sectors. As a consequence, effective communication and robust collaboration between professionals working in these sectors are lacking. Digital collaborative care platforms (ie, digital systems that facilitate communication and collaboration between health care professionals) are recognized as a promising solution to address the fragmentation of work-focused health care (health care that supports people on long-term sick leave in staying at or returning to work). A human-centered design (HCD) approach can help ensure that such platforms align with professionals’ needs by involving them throughout the design process. <strong>Objective:</strong> This study examines the experiences of (work-focused) health care professionals, including occupational physicians, insurance physicians, medical specialists, and general practitioners, during the design phase of a real-world HCD process for developing a digital platform to support collaborative care. The study specifically focused on understanding how these professionals perceive this collaborative approach. <strong>Methods:</strong> A mixed method study design was employed, combining observations of 17 design sessions with semistructured interviews with health care professionals as intended users of the platform. Observational data captured session dynamics, while interview data provided deeper insights into professionals’ experiences with the participatory HCD approach. <strong>Results:</strong> Health care professionals were generally motivated to contribute, driven by professional interest, social encouragement, or a desire to improve practice. They valued the open and informal atmosphere of the design sessions and described their role as actively sharing practical experiences and identifying bottlenecks in current practice. Participants emphasized the importance of clear goals, good preparation, and iterative involvement for meaningful engagement. Barriers identified included limited session time, constraints of virtual interaction, and uncertainty about the commercial context of the platform. Some professionals felt unsure about the relevance of their input or experienced limited interaction, especially when the session’s purpose was unclear. Others noted that the use of a mock-up platform as a conversational foundation, familiarity with similar system interfaces, and well-guided, structured discussions facilitated their input. Positive experiences included a sense of impact through involvement in the design process, note-taking as part of active user engagement, and a safe environment for open and constructive feedback. Participants recommended a clearer explanation of the platform’s broader aims in advance, enhanced participant preparation, and opportunities for multidisciplinary co-creation in future sessions. <strong>Conclusions:</strong> Health care professionals valued being part of the collaborative design process, but their engagement and perceived contribution were highly dependent on how the design sessions were facilitated. Structuring design sessions with clear expectations, preparatory tools, and opportunities for follow-up can support more effective, foundational co-creation in digital platform development for collaboration among professionals providing work-focused health care.
Exploring Influencing Factors of Medication Adherence Among Chinese Patients With Alzheimer Disease: Delphi Study Informing Future Artificial Intelligence–Supported Interventions
Background: Alzheimer disease (AD) affects cognition, treatment adherence, family connections, and health care resource allocation. Most patients with AD have low adherence to medication therapy due to the limitations associated with cognitive impairment. Therefore, increasing the involvement of patients and their family members in medication management is important to improve treatment outcomes and reduce the burden of care. Objective: This study explores the potential application of artificial intelligence (AI) in medication management for Chinese patients with early- to mid-stage AD focusing on enhancing medication adherence. The study first predicts and evaluates key factors through an online Delphi study, which provides a basis for their subsequent incorporation into the AI model as input variables to enable prediction of medication-taking behaviors. Since AI research in medication management for this population is still undeveloped, this paper further explores the multiple potentials of AI from a theoretical view, including drug dosage optimization, multidrug interaction detection, and family education support. It will provide a preliminary direction and theoretical basis for the development of an intelligent medication management system in the future. Methods: The exploratory online Delphi study with no modification predicted the key factors influencing medication adherence. Based on the results, the study confirmed the potential of AI to improve adherence. Participation by 12 experts in 3 rounds systematically assessed the core elements influencing patients’ adherence to their medication. Results: Family care, social support, environmental factors, emotional support, and patient behaviors were identified as the primary factors influencing medication adherence among Chinese patients with AD. These factors were validated and ranked through iterative Delphi rounds, with family care and social support receiving the highest importance scores. The Wilcoxon signed-rank test indicated no significant difference between rounds (=.06), supporting the stability of the consensus. These findings establish a foundational set of variables for AI systems that predict and enhance medication adherence. Conclusions: This study highlights the critical factors affecting medication adherence by Chinese patients with AD. It was designed as an exploratory online Delphi study to identify and prioritize key influencing factors, rather than to validate a specific AI-based system, and the findings provide a theoretical foundation for future AI-informed interventions. The results also indicate theoretical potential roles for AI in supporting medication management, such as optimizing drug dosage, detecting multidrug interactions, and enhancing family education.
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Community Health Worker Feedback on an mHealth Intervention for Hypertension in Rural Guatemala: Mixed Methods Formative Study
<strong>Background:</strong> Hypertension remains a leading global health challenge, particularly in low- and middle-income countries (LMICs), where limited health care infrastructure and resources restrict effective management. Community health workers (CHWs) are critical in delivering care in these settings, and when equipped with mobile health (mHealth) apps, they can greatly enhance chronic disease management. Involving CHWs in the design and development at all stages is essential for the success of such programs. However, relatively little research discusses CHW feedback on mHealth interventions. <strong>Objective:</strong> This study aims to evaluate CHW feedback on a hypertension program using a novel tablet-based mHealth tool designed for CHW hypertension diagnosis and management in rural Guatemala. <strong>Methods:</strong> We conducted a mixed-methods analysis as part of a pilot study in San Lucas Tolimán, Guatemala, involving 6 CHWs over a 6-month period. Quantitative data were collected using the System Usability Scale and Likert-scale surveys before and after study completion. Qualitative data were gathered through written surveys and focus group interviews conducted in Spanish by bilingual team members. These methods assessed the app’s ease of use, workflow integration, and cultural appropriateness. CHWs provided detailed perspectives on technical challenges, training adequacy, and patient engagement, which guided iterative refinements to both the mHealth app and the hypertension management program. <strong>Results:</strong> The mHealth app was generally well-received. Average System Usability Scale scores exceeded 70, surpassing established usability thresholds. Likert scale data revealed CHWs found the app to be useful and easy to use, but identified training protocols as areas for improvement. Qualitative analysis of focus groups and written surveys revealed 3 dominant themes. First, CHWs identified practical short-term needs, including slower and more comprehensive training sessions, simplified medication dosing regimens to reduce pill burden, and streamlined survey questions to shorten patient visit times. Second, CHWs raised larger structural concerns, including retention challenges related to financial compensation and misalignment between required clinical data collection and the cultural appropriateness of certain app questions. Third, CHWs highlighted program benefits, including improved patient care and hypertension management, empowerment through educational tools, and increased pride and community trust associated with the program. <strong>Conclusions:</strong> Our findings suggest that iteratively integrating user feedback into the development of mHealth interventions is key to improve usability, cultural appropriateness, and overall effectiveness of chronic disease management in resource-constrained settings. Due to the small number of CHW participants, as well as a reliance on self-reported perceptions, these findings should be interpreted as exploratory and hypothesis-generating rather than generalizable. This study contributes to the growing literature on mHealth apps for noncommunicable diseases in LMICs and provides insights into CHW experiences. Addressing the technical barriers and systemic challenges identified in this study can help improve future implementations of mHealth-enabled chronic disease programs in LMICs. <strong>Trial Registration:</strong>
First-Line Zongertinib Shows Strong Activity in HER2-Mutant Lung Cancer
For years, patients with HER2-mutant non–small cell lung cancer (NSCLC) have occupied a frustrating gap in precision oncology. While targeted therapies have transformed outcomes for EGFR– and ALK-driven lung cancers, HER2-mutant disease has lagged behind, with chemotherapy remaining the standard first-line option.
New data from the Phase Ia/Ib Beamion LUNG-1 trial, published in The New England Journal of Medicine, suggest that this may be changing. The oral HER2 inhibitor zongertinib demonstrated high response rates and durable clinical benefit in treatment-naïve patients, positioning it as a potential new first-line standard.
A long-standing unmet need
HER2 mutations occur in approximately 2–4% of NSCLC cases and are associated with aggressive disease and poor prognosis. Despite advances in targeted therapy across lung cancer, patients with HER2-driven tumors have historically had limited options, particularly in the first-line setting.
Until recently, treatment largely relied on chemotherapy, with or without immunotherapy, yielding modest outcomes, including progression-free survival typically under seven months.
“Just a few years ago, patients with this disease had no effective targeted therapies,” said John Heymach, MD, PhD, principal investigator of the study. “Now, healthcare providers have a HER2-targeted treatment option that can make a meaningful difference.”
High response rates and durability
In the trial, 74 previously untreated patients with advanced or metastatic HER2-mutant NSCLC received zongertinib at the selected dose of 120 mg daily. The results were striking.
A confirmed objective response was observed in 76% of patients, including both complete and partial responses. Tumor shrinkage was both rapid and durable, with a median duration of response of 15.2 months and median progression-free survival of 14.4 months.
These outcomes represent a substantial improvement over historical benchmarks and suggest that HER2-mutant NSCLC may finally benefit from the kind of targeted therapy success seen in other molecular subtypes.
“We observed unprecedented response rates for this cancer subtype,” Heymach said.
A more selective approach to HER2 targeting
One of the key differentiators of zongertinib is its selectivity. Unlike earlier HER2-targeted approaches, the drug inhibits HER2 while sparing wild-type EGFR, a closely related receptor whose inhibition is often associated with toxicity.
Zongertinib is described as an oral, irreversible tyrosine kinase inhibitor that selectively targets HER2 while minimizing EGFR-related side effects.
Clinically, this translated into a manageable safety profile. Most adverse events were low-grade, with relatively low rates of severe diarrhea and rash, common toxicities associated with EGFR inhibition. Serious complications such as interstitial lung disease were rare.
Activity in brain metastases
HER2-mutant NSCLC is also characterized by a high incidence of brain metastases, a major clinical challenge. Notably, the study demonstrated meaningful activity in this setting as well.
Among patients with active brain metastases, 47% achieved a confirmed intracranial response. Responses were also observed regardless of HER2 mutation subtype or baseline brain involvement, suggesting broad applicability across patient subgroups.
This intracranial activity is particularly significant, given the limited effectiveness of many systemic therapies in the central nervous system.
Implications for first-line treatment
The emergence of zongertinib as a first-line option marks a potential inflection point in the treatment of HER2-mutant NSCLC. For the first time, patients may be able to receive a targeted therapy at diagnosis, rather than progressing through less effective chemotherapy regimens.
The data have already translated into regulatory momentum. Zongertinib recently received accelerated FDA approval for this indication, reflecting both the strength of the clinical data and the unmet need in this population.
However, important questions remain. The current study is single-arm and lacks a direct comparison with standard-of-care therapies. A Phase III trial is ongoing to evaluate zongertinib against chemotherapy-based regimens in the first-line setting.
Positioning within a changing landscape
The broader treatment landscape for HER2-mutant lung cancer is also evolving. Antibody–drug conjugates such as trastuzumab deruxtecan have shown activity in previously treated patients, but are associated with notable toxicities and are typically used after progression.
Zongertinib’s oral administration, favorable safety profile, and first-line efficacy could shift treatment sequencing, potentially moving targeted therapy earlier in the disease course.
At the same time, resistance mechanisms are likely to emerge. Early data suggest that distinct resistance pathways may develop for tyrosine kinase inhibitors compared to antibody-based therapies, raising the possibility of sequential or combination strategies.
Looking ahead
As HER2-targeted therapies move into earlier lines of treatment, the focus will increasingly shift toward optimizing sequencing, managing resistance, and identifying combination approaches.
For now, the results from Beamion LUNG-1 provide strong evidence that HER2-mutant NSCLC, long considered a difficult-to-treat subtype, may finally be entering the era of precision oncology.
With high response rates, durable benefit, and activity in brain metastases, zongertinib offers a compelling new option, and a clear signal that the treatment paradigm for these patients is changing.
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