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Upfront management of brain metastases in oncogene‑addicted NSCLC - An EORTC survey
Ana Ortega-Franco1, Ilias Houda2, Mariana Brandão3
1The Christie NHS Foundation Trust, Manchester, United Kingdom; Cancer Research RUK National Biomarker Centre, Manchester, United Kingdom.
Background:
Brain metastases (BM) are common in patients with non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (AGA). The availability of next-generation targeted therapies (TT) with improved central nervous system activity has expanded systemic treatment options. However, the optimal upfront management of untreated symptomatic and asymptomatic BM remains uncertain due to limited trial data.
Methods:
A web-based survey was conducted by the EORTC Lung Cancer Group and distributed to EORTC and ESTRO members in June 2023-July 2024. The survey evaluated diagnostic approaches, access to TT and upfront management of untreated BM across 10 different AGA (including EGFR, ALK, ROS1, and others). Responses were analysed descriptively and stratified by neurological symptom status, AGA, intracranial objective response rate (icORR) of available TT, and medical specialty.
Results:
A total of 166 responses were analysed (91.0% of respondents worked in Europe, 47.6% were medical oncologist, 36.1% radiation oncologist, 9.6% pneumonologist, 4.8% clinical oncologist). For asymptomatic BM, 68.8% of physicians preferred upfront TT across AGA. In symptomatic BM, preferred upfront treatment included: local therapy alone (43.0%), TT alone (19.0%), local therapy or TT depending on other factors (35.4%). Treatment preferences for (a)symptomatic BM varied according to AGA, icORR of available TT, and medical specialty. In cases of brain oligoprogression, addition of local treatment and TT beyond progression was the most common option (92% of respondents). Across AGA, 35-52% of respondents opted to discontinue TT during brain radiotherapy with no clear preference for TT discontinuation timing.
Conclusions:
This work provides insights on the preferred upfront management of BM in patients with NSCLC and AGAs and underscores some of the challenges in this area, including extrapolation of data and uncertainty about how best to integrate TT with local therapies. Our findings might help identify priorities for future research and guideline development.
Insights
Physicians prefer upfront targeted therapy (TT) for asymptomatic brain metastases (BM) in non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA). For symptomatic BM, treatment varies, often involving local therapy or a combination approach.
Area of Science:
- Oncology
- Medical Research
- Clinical Practice
Background:
- Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients with actionable genomic alterations (AGA).
- Next-generation targeted therapies (TT) offer improved central nervous system (CNS) activity, expanding systemic treatment options.
- Optimal upfront management for untreated BM, both symptomatic and asymptomatic, remains unclear due to limited clinical trial data.
Purpose of the Study:
- To survey physician preferences on the upfront management of untreated brain metastases (BM) in non-small cell lung cancer (NSCLC) patients with actionable genomic alterations (AGA).
- To explore how factors such as neurological symptom status, specific AGA, intracranial objective response rate (icORR) of TT, and medical specialty influence treatment decisions.
Main Methods:
- A web-based survey was distributed to EORTC and ESTRO members.
- The survey assessed diagnostic approaches and upfront management strategies for BM across 10 different AGAs.
- Responses were analyzed descriptively and stratified by key clinical and demographic factors.
Main Results:
- For asymptomatic BM, 68.8% of physicians favored upfront TT.
- For symptomatic BM, preferred upfront treatments included local therapy alone (43.0%), TT alone (19.0%), or a combination approach (35.4%).
- Treatment preferences varied significantly based on AGA, TT's icORR, and medical specialty. Most respondents (92%) opted for combined local treatment and TT for brain oligoprogression.
Conclusions:
- This survey provides valuable insights into current physician preferences for managing BM in NSCLC with AGAs.
- It highlights challenges related to data extrapolation and integrating TT with local therapies.
- Findings can inform future research priorities and guideline development for optimal BM management.
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