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InOncology.com

Brain Metastases

As many as 40% of patients diagnosed with non-small cell lung cancer (NSCLC) may develop brain metastases during the course of their disease,1 and the risk may be greater in those who harbour an epidermal growth factor receptor (EGFR) mutation.2 The presence of brain metastases is an important factor influencing the selection of the optimal first-line treatment in EGFR mutation-positive NSCLC.3

Risk of CNS progression in patients who were treated with afatinib in LUX-Lung 3, 6 and 7

In patients with baseline brain metastases who were treated with afatinib* in LUX-Lung 3 and LUX-Lung 6, the cumulative incidence of central nervous system (CNS) progression was 40% lower than that of non-CNS progression (31% vs 52%);3 at 1 year, the risk of CNS progression in these patients was 24.5%.4 In patients without brain metastases who were treated with afatinib in LUX-Lung 3, LUX-Lung 6 and LUX-Lung 7, the cumulative incidence of CNS progression was 92% lower than that of non-CNS progression (6% vs 78%).3

Risk of progression in patients with baseline brain metastases who were treated with afatinib in LUX-Lung 3 and 6

Risk of progression in afatinib patients with brain metastases in LUX-Lung 3 and 6

CNS, central nervous system; PD, progressive disease.

Risk of progression in patients without baseline brain metastases who were treated with afatinib in LUX-Lung 3, 6 and 7

Risk of progression in afatinib patients without brain metastases in LUX-Lung 3, 6 and 7

CNS, central nervous system; PD, progressive disease.

Efficacy of afatinib in patients with brain metastases in LUX-Lung 3, 6 and 7

Data from LUX-Lung 3 and LUX-Lung 6 demonstrate the efficacy of afatinib versus chemotherapy in patients with stable brain metastases at baseline. Preplanned subgroup analyses were performed in patients with brain metastases and common EGFR mutations in LUX-Lung 3 (n=35) and LUX-Lung 6 (n=46).5 In a post-hoc combined analysis of patients with brain metastases from both studies (n=81), median PFS was significantly longer with afatinib than with chemotherapy (8.2 vs 5.4 months; hazard ratio [HR]=0.50; 95% confidence interval [CI]: 0.27–0.95; p=0.03).5

PFS outcomes for patients with brain metastases: combined LUX-Lung 3 and 6 analysis

Figure for PFS in patients with brain metastases; afatinib vs chemotherapy

CI, confidence interval; HR, hazard ratio; PFS, progression-free survival.

In patients with brain metastases in LUX-Lung 7, progression-free survival (PFS) was improved with afatinib versus gefitinib (HR=0.76) and the magnitude of the increase was similar to that observed in patients without brain metastases (HR=0.74).6

Real-world evidence of the efficacy of afatinib in Korean patients with EGFR mutation-positive NSCLC and brain metastases

A retrospective study was carried out in 165 Korean patients with recurrent or metastatic EGFR mutation-positive NSCLC.7 Forty-three percent of patients had brain metastases before starting first-line treatment with afatinib. In patients with brain metastases at baseline who had not received radiotherapy for brain tumours, median PFS was 15.7 months (n=39).7 Of these patients, 29 had follow up magnetic resonance imaging data and 55% of these patients were described as having significantly decreased brain metastases with afatinib treatment.7

PFS in Korean patients with and without brain metastases

PFS in Korean patients with brain metastases

GKS, Gamma Knife surgery; PFS, progression-free survival; WBRT, whole-brain radiotherapy.

Real-world evidence of the efficacy of afatinib in Taiwanese patients with advanced EGFR mutation-positive NSCLC and brain metastases

In a retrospective study in 422 Taiwanese patients with advanced EGFR mutation-positive NSCLC, 104 patients received afatinib as first-line treatment.8 Median PFS in patients with and without brain metastases at baseline was 9.9 and 13.1 months, respectively.8

In another retrospective Taiwanese study in patients with advanced EGFR mutation-positive lung adenocarcinoma, 42 out of 140 patients had brain metastases at baseline.9 Patients with initial brain metastases had a poorer Eastern Cooperative Oncology Group performance status than those without brain metastases (p=0.003).9 Median PFS in patients with and without brain metastases at baseline was 9.2 months and 14.9 months, respectively (HR=2.29; 95% CI: 1.46–3.60; p<0.001).9

PFS in Taiwanese patients with and without brain metastases

PFS in Taiwanese patients with brain metastases

CI, confidence interval; HR, hazard ratio; PFS, progression-free survival.

Efficacy of afatinib in a smaller case series in patients with symptomatic brain metastases and in a study in patients with leptomeningeal carcinomatosis

In a case series in patients with symptomatic brain metastases, first-line treatment with afatinib was also shown to induce complete remission that lasted ≥6 months in five EGFR mutation-positive NSCLC patients who had declined whole-brain radiation therapy.10 Afatinib has also shown efficacy in a prospective study of 11 patients with EGFR mutation-positive NSCLC who had leptomeningeal carcinomatosis. The median cerebrospinal concentration of afatinib in this study was 1.4 ng/mL.11 This equates to a molar concentration of 2.9 nM, which is clearly above the IC50 value for the EGFR (0.5 nM).12,13

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References

1

Ali A, et al. Curr Oncol 2013;20(4):e300–6.

2

Shin DY, et al. J Thorac Oncol 2014;9(2):195–9.

3

Girard N. Future Oncol 2018;14(11):1117–1132.

4

Data on file. Boehringer Ingelheim.

5

Schuler M, et al. J Thorac Oncol 2016;11(3):380–90.

6

Park K, et al. Lancet Oncol 2016;17(5):577–89.

7

Kim Y, et al. Poster presented at WCLC 2017 (Poster P3.01-023).

8

Tu C-Y, et al. Oncotarget 2018;9(36):24237–47.

9

Liang S-K, et al. Oncotarget 2017;8(52):90430–43.

10

Hochmair M, et al. Anti-Cancer Drugs 2016;27(9):914–5.

11

Tamiya A, et al. Anticancer Res 2017;37(8):177–82.

12

Li D, et al. Oncogene 2008;27(34):4702–11.

13

Solca F, et al. J Pharmacol Exp Ther 2012;343(2):342–50.

*Afatinib is approved in more than 80 markets, including the EU, Japan, Taiwan and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list, please click here. Registration conditions differ internationally; please refer to locally approved prescribing information.

 

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Last updated: October 2018