Real‑world challenges in ALK+ NSCLC care

By Laura Boyd

​​In routine practice, patients with ALK+ NSCLC frequently experience adverse events, treatment interruptions, and dose modifications that are not fully anticipated from clinical trial data​

Anaplastic lymphoma kinase-positive (ALK+) non–small cell lung cancer (NSCLC) accounts for approximately 2–7% of cases and is frequently associated with aggressive disease and a high incidence of central nervous system involvement.^1,2 Although next‑generation ALK tyrosine kinase inhibitors (TKIs) have transformed systemic and intracranial disease control, translating these outcomes into routine practice remains challenging.³ Real‑world populations differ substantially from clinical trial cohorts, with broader demographic and clinical diversity contributing to variable tolerability, adverse‑event (AE) burden, and treatment continuity.⁴ In parallel, differences between patient and clinician priorities and inconsistent multidisciplinary (MDT) coordination add further complexity to first‑line (1L) treatment selection and long‑term management in advanced ALK+ NSCLC.⁵

How do real‑world patient populations with ALK+ NSCLC differ from clinical trial cohorts?

Real‑world patient populations with ALK+ NSCLC differ from clinical trial cohorts in demographic, geographic, clinical, and socioeconomic diversity.⁴ These differences are associated with more frequent treatment interruptions, dose modifications, and clinically significant AEs in routine practice, highlighting challenges in translating trial‑based tolerability data to everyday clinical care.^6,7

Why do treatment interruptions and modifications occur frequently with ALK TKIs outside trials?

Treatment interruptions and dose modifications occur frequently with ALK TKIs outside trials due to AE patterns that are less predictable in routine practice.^6,7

Metabolic, neurologic, gastrointestinal, and cardiovascular toxicities may progress without early recognition, leading clinicians to adjust dosing or interrupt therapy to manage tolerability.^8,9

What challenges affect early recognition and escalation of ALK TKI–related adverse events?

Early recognition and escalation of ALK TKI–related AEs are challenged by limited patient readiness at treatment initiation.¹⁰ In routine practice, many patients lack clear guidance on^11,12:

• Symptom monitoring and early warning signs
• Day‑to‑day treatment expectations
• Clear thresholds for escalation and contacting the care team

As a result, delays in reporting may allow manageable toxicities to worsen and disrupt treatment continuity.¹³ 

What limits consistent application of shared decision‑making in ALK+ NSCLC care?

Consistent application of shared decision‑making in ALK+ NSCLC care is limited by difficulty identifying preference‑sensitive decisions, scarce structured decision aids, and divergent priorities between patients and clinicians.^5,14

These barriers are particularly relevant in 1L ALK TKI selection, where benefit–risk trade-offs are complex and comparative data are limited.^12,15

How does variability in MDT coordination affect continuity of care for patients receiving ALK TKIs?

Variability in MDT coordination affects continuity of care by contributing to¹⁶:

• Inconsistent communication
• Delayed responses to patient‑reported symptoms
• Fragmented follow‑up

Differences in MDT workflows and digital tool use can hinder timely information sharing across disciplines, complicating long‑term management of patients receiving ALK TKIs.^11,17

Key takeaways

• Real‑world patients with ALK+ NSCLC differ from trial populations, contributing to higher rates of AEs, dose modifications, and treatment interruptions
• Limited patient readiness at treatment initiation can delay AE recognition and escalation, disrupting treatment continuity
• First‑line ALK TKI selection is complicated by differing patient and clinician priorities and limited structured support for shared decision‑making
• Variability in MDT coordination and digital tool use can hinder timely communication and long‑term management

References

1. Shaw, 2009. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. https://www.doi.org/10.1200/jco.2009.22.6993
2. Sakamoto, 2021. Characteristics of central nervous system progression in non-small cell lung cancer treated with crizotinib or alectinib. https://www.doi.org/10.1002/cnr2.1414
3. Shalata, 2025. Efficacy of tyrosine kinase inhibitors in ALK and EGFR-mutated non-small cell lung cancer with brain metastases. https://www.doi.org/10.3390/medsci13030200
4. Gibson, 2021. Retrospective real-world outcomes for patients with ALK-rearranged lung cancer receiving ALK receptor tyrosine kinase inhibitors. https://www.doi.org/10.1016/j.jtocrr.2021.100157
5. Shao, 2026. Patient preference for first-line treatments of ALK-positive metastatic non-small cell lung cancer: A discrete choice experiment. https://www.doi.org/10.1186/s12885-025-15509-7
6. Wang, 2023. ALK inhibitor treatment patterns and outcomes in real-world patients with ALK-positive non-small-cell lung cancer: A retrospective cohort study. https://www.doi.org/10.1007/s11523-023-00973-7
7. Mudumba, 2025. Real-world costs, treatment patterns, and clinical outcomes associated with treatments for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. https://www.doi.org/10.18553/jmcp.2025.31.9.890
8. Liu, 2024. A pragmatic guide for management of adverse events associated with lorlatinib. https://www.doi.org/10.1016/j.lungcan.2024.107535
9. Gristina, 2020. The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer. https://www.mdpi.com/1424-8247/13/12/474
10. Fisher, 2024. Evidence-based recommendations for education provided to patients and families regarding the adverse events of ALK and MEK inhibitors: A systematic review from the children's oncology group. https://www.doi.org/10.1177/27527530231206101
11. 2025. IQVIA Healthcare Analysis Agent: Internal proprietary report.
12. Le, 2024. P1.12B.05 Patient and oncologist preferences for ALK+ advanced non-small cell lung cancer tyrosine kinase inhibitor treatments. https://www.doi.org/10.1016/j.jtho.2024.09.364
13. Rolfo, 2015. Adverse event management in anaplastic lymphoma kinase-positive non-small cell lung cancer. https://www.doi.org/10.17925/EOH.2015.11.02.94
14. Klok, 2025. Shared decision-making in the treatment of non-small cell lung cancer stage I-IV: Perspectives from patients and clinicians. https://www.doi.org/10.1136/bmjresp-2024-003114
15. Bauman, 2025. Order of treatment with ALK inhibitors and its effect on people with lung cancer in the real world: A plain language summary. https://www.doi.org/10.1080/14796694.2025.2489319
16. Srivastava, 2025. Impact of multidisciplinary team care on patient-reported outcomes in patients with lung cancer: A systematic review. https://www.doi.org/10.3390/curroncol32120697
17. Powell, 2014. Multidisciplinary team management in thoracic oncology: More than just a concept? https://www.doi.org/10.1183/09031936.00150813

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