Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases

Dutta, Sunil W.; Mack, Marie; Aliotta, Eric; Ward, Kristin; Muller, Donald A.; Larner, James M.; Fadul, Camilo E.; Hall, Richard D.; Gentzler, Ryan D.; Sheehan, Jason P.

doi:10.1007/s11060-020-03615-4

Cited by 8 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For ALK+ NSCLC, Thomas 10 also found no evident difference between TKI and CNS RT + TKI groups for the time to intracranial progression (18.1 vs. 21.8 months, p = 0.65). Moreover, in a retrospective study, for ALK–rearranged or EGFR–mutant lung cancer, Dutta et al., 12 reported that patients treated solely with TKIs achieved a 94% partial intracranial response at 3 months, whereas 58% of those receiving TKIs combined with radiation achieved this outcome. Correspondingly, ALK+ patients with BM often do not receive routine intracranial radiotherapy in clinical practice, possibly due to the superior intracranial control offered by ALK‐TKIs alone 10–12 …”

Section: Discussionmentioning

confidence: 99%

Comparison of clinical and MRI features of brain metastases between ALK+ and ALK‐ NSCLC

Ren,

Zhang,

Lei

et al. 2024

Cancer Medicine

View full text Add to dashboard Cite

BackgroundNon‐small‐cell lung cancer (NSCLC) is the primary cause of brain metastases (BM). This study aimed to investigate differences in clinical and magnetic resonance imaging (MRI) features of BM between anaplastic lymphoma kinase (ALK) gene fusion (ALK+) and ALK wild‐type (ALK‐) NSCLC, and to preliminarily assess the efficacy of radiotherapy for treating BM.MethodsA retrospective analysis included 101 epidermal growth factor receptor (EGFR)‐ NSCLC patients with BM: 41 with ALK gene fusion and 60 being ALK‐. The brain MRI and clinical features were compared between different ALK status using the multivariate analysis, and a nomogram was constructed to predict ALK gene fusion. Fifty‐six patients who did not undergo cerebral surgery and had complete pre‐ and post‐ treatment data were further divided based on whether they received radiotherapy. Log‐rank test was used to compare the short‐term effect of treatment between the two groups under different genotypes.ResultsALK+ BM exhibited decreased peritumoral brain edema size, lower peritumoral brain edema index (PBEI), and a more homogeneous contrast enhancement pattern compared to ALK‐ BM. Age (OR = 1.04; 95%CI: 1.02–1.06), time to BM (OR = 1.50; 95% CI: 1.04–2.14), PBEI (OR = 1.26; 95% CI: 0.97–1.62), smoking status (smoking index >400 vs. non‐smoking status: OR = 1.42; 95% CI: 0.99–2.04) and contrast enhancement pattern (OR = 1.89; 95% CI: 1.28–2.78) were associated with ALK gene fusion. A nomogram based on these variables demonstrated acceptable predictive efficiency (AUC = 0.844). In the ALK+ group, patients who received radiotherapy did not show increased disease control rate (DCR) or progression‐free survival (PFS). In contrast, in the ALK‐ group, those who received radiotherapy had improved objective response rate (ORR), DCR, and PFS compared to those who were only treated with systemic therapy.ConclusionsThe clinical and MRI features of BM can indicate the status of ALK in NSCLC. In the ALK‐ group, patients who received radiotherapy showed higher ORR, DCR, and PFS compared to those who did not.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparison of clinical and MRI features of brain metastases between ALK+ and ALK‐ NSCLC

Ren,

Zhang,

Lei

et al. 2024

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…27 Patients with brain metastasis harboring EGFR T790M, in whom osimertinib was used alone, had reasonable IC‐ORR and IC‐DCR, which reached 55.0% and 77.5%, respectively; however, the IC‐PFS was only 7.6 months. 27 Dutta et al 28 reported that EGFR‐TKIs alone or EGFR‐TKIs with irradiation had a similar ORR and intracranial PFS (IC‐PFS); meanwhile, patients with high intracranial burden and neurological symptoms at diagnosis had similar IC‐PFS and OS compared with those with low burden and absence of neurological symptoms. In our study, the IC‐ORR was 82.7%, while the IC‐PFS reached 22.0 months, which was comparable to the extracranial ORR and extracranial PFS.…”

Section: Discussionmentioning

confidence: 99%

Osimertinib combined with bevacizumab as the first‐line treatment in non‐small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations

et al. 2023

View full text Add to dashboard Cite

Background The efficacy and safety of osimertinib combined with bevacizumab in non‐small cell lung cancer (NSCLC) patients with brain metastasis harboring epidermal growth factor receptor (EGFR) mutations have not been fully studied. Methods Treatment‐naïve NSCLC patients with brain metastasis harboring EGFR‐activating mutations were treated with osimertinib 80 mg oral daily and bevacizumab 15 mg/kg intravenously on day 1, repeated every 21 days, until disease progression, intolerable toxicity, or death. The primary endpoint was the median progression‐free survival (mPFS), and the secondary endpoints were the median overall survival (mOS), response rates, and toxicities. This study has been registered in http://clinicaltrials.gov (NCT05104281) and is ongoing. Results A total of 52 Chinese patients were enrolled, of whom 17 harbored EGFR 19 del and 35 harbored EGFR L858R mutation. The objective response rate (ORR) was 75.0% and the disease control rate (DCR) was 96.2%; the mPFS was 17.0 months (95% CI: 11.46–22.54), while the mOS was not reached. The mPFS was 20.0 months (95% CI: 14.56–25.44) and was 17.0 months (95% CI: 13.28–20.72) for patients harboring EGFR 19 del and EGFR L858R mutation (p = 0.844), respectively. The intracranial ORR was 82.7%, and the intracranial mPFS was 22.0 months (95% CI: 2.92–41.08).The main adverse events were mild‐to‐moderate hand‐foot syndrome, diarrhea, hypertension, and proteinuria. Three patients developed grade III proteinuria, while five patients developed grade III hypertension; they permanently discontinued bevacizumab treatment. Conclusions Osimertinib combined with bevacizumab shows promising results in EGFR‐mutated NSCLC patients with brain metastasis, and the side effects are tolerable.

show abstract

“…There is emerging evidence that systemic therapy may be preferred in the upfront setting over the localized therapies described above, particularly in patients with asymptomatic intracranial disease ( 50 , 52 ). Even in situations when local therapy would be considered standard, such as in patients with symptomatic or large brain metastases, retrospective studies suggest that tyrosine kinase inhibitors (TKIs) demonstrate significant intracranial activity with associated clinical improvement ( 67 , 68 ). Thus, effective systemic therapies may delay or eliminate local strategies with associated neurologic morbidity, such as WBRT.…”

Section: Management Of Alk -Positive Brain Metastasesmentioning

confidence: 99%

Targeting lung cancer brain metastases: a narrative review of emerging insights for anaplastic lymphoma kinase (ALK)-positive disease

Nelson¹,

Wang²

2023

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background and Objective: Lung cancer is commonly associated with brain metastasis formation, and certain subtypes, such as anaplastic lymphoma kinase (ALK) rearranged disease, have an especially high propensity for early and frequent central nervous system (CNS) involvement for which treatment can be challenging. Historical management has centered on surgery and radiation therapy (RT), which persist as mainstays of treatment for large, symptomatic lesions and widespread CNS disease. To date, sustained disease control remains elusive, and the role for effective systemic adjunctive therapies is clear. Here we discuss the epidemiology, genomics, pathophysiology, identification, and management of lung cancer brain metastases with a particular emphasis on systemic treatment of ALK-positive disease according to the best available evidence.Methods: Review of PubMed and Google Scholar databases as well as ClinicalTrials.gov provided background and seminal trials for the local and systemic management of ALK rearranged lung cancer brain metastases.

show abstract

Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases

Cited by 8 publications

References 25 publications

Comparison of clinical and MRI features of brain metastases between ALK+ and ALK‐ NSCLC

Comparison of clinical and MRI features of brain metastases between ALK+ and ALK‐ NSCLC

Osimertinib combined with bevacizumab as the first‐line treatment in non‐small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations

Targeting lung cancer brain metastases: a narrative review of emerging insights for anaplastic lymphoma kinase (ALK)-positive disease

Contact Info

Product

Resources

About