Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies

Popat, Sanjay; Ahn, Myung‐Ju; Ekman, Simon; Leighl, Natasha B.; Ramalingam, Suresh S.; Reungwetwattana, Thanyanan; Tsuboi, Masahiro; Wu, Yi‐Long; Yang, James Chih‐Hsin

doi:10.1007/s11523-022-00941-7

Cited by 13 publications

(10 citation statements)

References 87 publications

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“…Approximately 30%-50% of these patients develop CNS metastases within 5 years of diagnosis, 3-5 and the incidence is rising owing to improved survival and enhanced detection. 2,6 Treatment is challenging as many drugs cannot cross the blood-brain barrier or are effluxed, making the CNS a sanctuary site for metastases and limiting the ability of systemic treatments to affect intracranial disease. 2…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…CNS metastases negatively affect patient quality of life (QoL) and prognosis 1,2 and are common in patients with epidermal growth factor receptor (EGFR)-mutated advanced nonsmall-cell lung cancer (NSCLC). Approximately 30%-50% of these patients develop CNS metastases within 5 years of diagnosis, [3][4][5] and the incidence is rising owing to improved survival and enhanced detection.…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 30%-50% of these patients develop CNS metastases within 5 years of diagnosis, [3][4][5] and the incidence is rising owing to improved survival and enhanced detection. 2,6 Treatment is challenging as many drugs cannot cross the blood-brain barrier or are effluxed, making the CNS a sanctuary site for metastases and limiting the ability of systemic treatments to affect intracranial disease. 2 EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the recommended first-line treatment for certain patients with EGFR-mutated advanced NSCLC and brain metastases; some guidelines specifically recommend osimertinib.…”

Section: Introductionmentioning

confidence: 99%

“…2,6 Treatment is challenging as many drugs cannot cross the blood-brain barrier or are effluxed, making the CNS a sanctuary site for metastases and limiting the ability of systemic treatments to affect intracranial disease. 2 EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the recommended first-line treatment for certain patients with EGFR-mutated advanced NSCLC and brain metastases; some guidelines specifically recommend osimertinib. [7][8][9] Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitizing and T790M resistance mutations, with demonstrated efficacy in EGFR-mutated NSCLC, including CNS metastases.…”

Section: Introductionmentioning

confidence: 99%

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CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor–Mutated Advanced Non–Small-Cell Lung Cancer

Jänne,

Planchard,

Kobayashi

et al. 2024

JCO

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PURPOSE We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor ( EGFR)–mutated advanced non–small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor–Mutated Advanced Non–Small-Cell Lung Cancer

Jänne,

Planchard,

Kobayashi

et al. 2024

JCO

Self Cite

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Current and Emerging Treatment Options for Patients with Metastatic EGFR-Mutated Non-small Cell Lung Cancer After Progression on Osimertinib and Platinum-Based Chemotherapy: A Podcast Discussion

Patel,

Patel

2023

Adv Ther

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Patients with metastatic epidermal growth factor receptor ( EGFR )-mutated non-small cell lung cancer (NSCLC) are widely treated with osimertinib, the preferred first-line treatment option. However, disease progression inevitably occurs, driven by EGFR -dependent or EGFR -independent mechanisms of resistance. Platinum-based chemotherapy is the recommended treatment following progression with osimertinib but responses to platinum-based chemotherapy are transient. Salvage therapies, which are used after progression on platinum-based chemotherapy, have poor clinical outcomes in addition to substantial toxicity. In this podcast, we discuss the current treatment landscape and emerging therapeutic options for patients with metastatic EGFR -mutated NSCLC whose disease has progressed following treatment with osimertinib and platinum-based chemotherapy. Podcast audio available for this article. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02680-1.

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Development of brain metastases in patients managed with non-curative thoracic radiotherapy for stage II/III non-small cell lung cancer

Nieder,

Aanes,

Stanisavljevic

et al. 2024

Discov Onc

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Background This retrospective study analyzed the incidence of subsequent brain metastases after palliative radiotherapy or chemoradiation in patients with stage II/III non-small cell lung cancer (NSCLC). Risk factors for brain metastases development and survival after diagnosis were evaluated. Methods Different baseline parameters including but not limited to age, stage and target volume size were assessed. Outcomes were abstracted from electronic health records. Uni- and multivariate tests were performed. Results The study included 102 patients and found an actuarial risk of brain metastases of 15% (standard error ± 4) at one year and 20% (± 5) at two years. The maximum time interval was 15 months from start of radiation treatment. A non-significant survival difference was observed (median 12 months without versus 8.3 months with brain metastases, p = 0.21). Incidence was higher in patients with N2/3 stage, larger planning target volume size, and younger age (univariately significant factors). Trends were seen for stage III and adenocarcinoma histology. The multivariate analysis confirmed age as the most important risk factor. Conclusion The risk of brain metastases development was comparable to that reported in studies of curative chemoradiation. All events occurred within 15 months of follow-up, suggesting that long-term surveillance imaging may not be warranted. Patients younger than 60 years had a very high risk of brain metastases development.

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Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies

Cited by 13 publications

References 87 publications

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor–Mutated Advanced Non–Small-Cell Lung Cancer

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor–Mutated Advanced Non–Small-Cell Lung Cancer

Current and Emerging Treatment Options for Patients with Metastatic EGFR-Mutated Non-small Cell Lung Cancer After Progression on Osimertinib and Platinum-Based Chemotherapy: A Podcast Discussion

Development of brain metastases in patients managed with non-curative thoracic radiotherapy for stage II/III non-small cell lung cancer

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