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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 500-502

A case of multifocal uveal metastases from T790M-mutated non-small-cell lung carcinoma with an unexpected reaction to Osimertinib


Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin Province, China

Date of Submission04-Aug-2021
Date of Acceptance18-Nov-2021
Date of Web Publication13-Apr-2022

Correspondence Address:
Wen-Song Zhang
Department of Ophthalmology, The Second Hospital of Jilin University, Yatai Street, Changchun - 130 000, Jilin Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_2061_21

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  Abstract 


Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in the treatment of metastatic non-small-cell lung carcinoma (NSCLC) patients with targetable EGFR-T790M mutations. We describe the case of a 61-year-old Chinese female confirmed with multifocal uveal metastases from T790M-mutated NSCLC after developing acquired resistance to icotinib (a first-generation EGFR-TKI). Therefore, she was instituted on oral osimertinib. The uveal masses were reported to completely disappear on anterior segment examination, ultrasound biomicroscopy (UBM), and ocular color doppler flow imaging (CDFI) after 41 weeks. However, the patient got worse and eventually died from systemic metastases 4 months later.

Keywords: Epidermal growth factor receptor, non-small-cell lung carcinoma, Osimertinib, tyrosine kinase inhibitors, uveal metastases


How to cite this article:
Xu DL, Zhu YY, Wu XZ, Huang J, Zhang WS. A case of multifocal uveal metastases from T790M-mutated non-small-cell lung carcinoma with an unexpected reaction to Osimertinib. Indian J Ophthalmol Case Rep 2022;2:500-2

How to cite this URL:
Xu DL, Zhu YY, Wu XZ, Huang J, Zhang WS. A case of multifocal uveal metastases from T790M-mutated non-small-cell lung carcinoma with an unexpected reaction to Osimertinib. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 Dec 3];2:500-2. Available from: https://www.ijoreports.in/text.asp?2022/2/2/500/342922



Ocular involvement occurs in 0.2%–7% cases of metastatic lung cancer.[1] The metastatic sites mainly involve the choroid (88%), the iris (10%), and the ciliary body (2%).[1] These metastases are typically treated with external beam radiation therapy (ERBT), which has been reported to cause tumor regression in up to 94%.[2] However, with the longer life expectancy of patients, long-term complications of radiotherapy have attracted considerable attention.[2] In recent years, accompanying the advancement in targeted therapy, EGFR-TKIs have demonstrated tremendous potentials in the treatment of NSCLC patients with uveal metastasis. Herein, our report shows the effectiveness of osimertinib monotherapy for multifocal uveal metastases in an NSCLC patient carrying EGFR-T790M mutations.


  Case Report Top


A 61-year-old never-smoking Chinese female presented with a complaint of blurred vision and ocular pain in the left eye for 1 month. On examination, the best-corrected visual acuity (BCVA) was 1.0 logMAR in both eyes (OU). The intraocular pressure (IOP) was 15 mm Hg in the right eye (OD) and 50 mm Hg in the left eye (OS). Anterior segment examination of the left eye showed moderate corneal edema, shallow anterior chamber, and irregular pupil with pupillary light reflex partly restricted. In addition, a 1 mm × 2 mm coloboma was noted on the iris surface at 4 o'clock to 6 o'clock positions [Figure 1]a. Central visual field examination revealed a paracentral scotoma OD and a superior arcuate scotoma with an inferior nasal step OS. UBM revealed the root of the iris surface was bowed anteriorly and the anterior chamber became shallower OU, which made the angle narrow. Furthermore, it showed noticeably atrophy of the inferotemporal ciliary body and partial coloboma of anterior chamber angle OS [Figure 2]a. CDFI did not reveal any lesions at the posterior segment OS [Figure 3]a. The patient was initially diagnosed with acute angle-closure glaucoma (preclinical phase OD and chronic phase OS).
Figure 1: The anterior segment examination of the left eye. (a) A 1 mm × 2 mm coloboma was seen on the inferotemporal iris surface after taking osimertinib. (b) A pinkish-white iris lump spread over the inferotemporal iris surface

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Figure 2: Ultrasound biomicroscopy (UBM) of the left eye. (a) The atrophy of the inferotemporal ciliary body and partial coloboma of anterior chamber angle were seen after taking osimertinib. (b) The inferotemporal iris and ciliary body existed a tuft of inhomogeneous hypoechoic within a clear boundary, and the inferior ciliary body showed a middle-strong echogenic area

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Figure 3: Ocular color doppler flow imaging (CDFI) of the left eye. (a) No abnormal lesions were observed in the choroid after taking osimertinib. (b) The superotemporal optic disc existed low homogeneous echogenic area, in which scattered bloodstream signal existed

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A detailed history was ascertained; the patient had a history of pulmonary adenocarcinoma 32 months ago. Meanwhile, PET-CT revealed brain and vertebral metastases. Genetic analysis demonstrated deletions of exon 19 in the EGFR mutation. Thus, she was diagnosed with stage T4N2M1b (stage IV). She was offered icotinib monotherapy. However, CT reexamination denoted slight changes in lung lesions 42 weeks ago. She took a lung carcinoma biopsy again, which manifested T790M mutations of the EGFR gene. Meantime, she began to develop ocular symptoms of redness and ocular pain OS. Slit-lamp examination revealed a pinkish-white vascularized iris lump measuring 4 mm × 2 mm at 4 o'clock to 6 o'clock positions OS [Figure 1]b. UBM revealed inferotemporal iris and ciliary body existing a tuft of inhomogeneous hypoechoic within a clear boundary, and inferior ciliary body showing a middle-strong echogenic area OS [Figure 2]b. CDFI observed superotemporal optic disc existed low homogeneous echogenic area, in which CDFI showed scattered bloodstream signal, within a clear boundary OS [Figure 3]b. Eventually, the patient was diagnosed with multifocal uveal metastases from pulmonary adenocarcinoma. She took ophthalmologists' and oncologists' advice and started to treat with osimertinib 80 mg/day.

The patient had taken osimertinib for 41 weeks before coming to our hospital. Combining the history of lung cancer with using osimertinib and comparing the previous uveal lesions with the present results, we concluded uveal metastases had regressed following osimertinib monotherapy. Finally, the patient approved and underwent trabeculectomy, and ocular symptoms were remitted with post-operative intraocular pressure controlled. Unfortunately, the patient died from diffuse systemic metastasis 4 months later.


  Discussion Top


The EGFR protein, a receptor tyrosine kinase, can be specifically activated by corresponding extracellular ligands, and has functions in migration, proliferation, and cell survival.[3] EGFR mutations in lung adenocarcinoma are detected in about 10%–50% of NSCLC, and this type of tumor cell multiplication depends almost on the EGFR signaling pathways.[3],[4] Thus, any interruption of these pathways may cause tumor regression.[4] EGFR-TKIs block the activation of downstream signaling induced by EGFR by combining with the ATP-binding pocket, which eventually inhibits tumor growth.[5] However, most EGFR-mutant NSCLC patients will inevitably develop acquired resistance to 1st and 2nd generation EGFR TKI within 10–14 months, which is due to T790M mutations.[6] To overcome this resistance, osimertinib (AZD9291) came into being, which received approval from the China Food and Drug Administration (CFDA) for therapy in the case of locally advanced or metastatic NSCLC patients with targetable EGFR-T790M mutations who have progressed on or after EGFR-TKI therapy in March 2017.[7]

In consideration of genetic similarities to T790M-mutated NSCLC, osimertinib has begun to be used for uveal metastases and effectively facilitated tumor regression. There have been three case reports recording the effectiveness of osimertinib on uveal metastases from T790M-mutated NSCLC, including two about unifocal choroidal metastasis and one about unifocal iris metastasis.[8],[9],[10] Our patient had not only similar results with regression of iris and choroidal mass but also surprising results with resolution of ciliary mass after 41 weeks of osimertinib.


  Conclusion Top


Our case showed the effectiveness of osimertinib monotherapy for multifocal uveal metastases in the case of an NSCLC patient carrying EGFR-T790M mutations. To alleviate the symptom and step down the progression, osimertinib should be early and continuously recommended for uveal metastases in NSCLC patients who are diagnosed with T790M mutation. Further studies are needed to prove if osimertinib has long-term outcomes in uveal metastases of EGFR-T790M mutation-positive NSCLC patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Shah SU, Mashayekhi A, Shields CL, Walia HS, Hubbard GB 3rd, Zhang J, et al. Uveal metastasis from lung cancer: Clinical features, treatment, and outcome in 194 patients. Ophthalmology 2014;121:352-7.  Back to cited text no. 1
    
2.
Konstantinidis L, Damato B. Intraocular metastases--A review. Asia Pac J Ophthalmol (Phila) 2017;6:208-14.  Back to cited text no. 2
    
3.
Suster DI, Mino-Kenudson M. Molecular pathology of primary non-small cell lung cancer. Arch Med Res 2020;51:784-98.  Back to cited text no. 3
    
4.
Nair AG, Asnani HT, Mehta VC, Mehta SV, Pathak RS, Palkar AH, et al. Tyrosine kinase inhibitors in the treatment of choroidal metastases from non-small-cell lung cancer: A case report and review of literature. Ocul Oncol Pathol 2017;3:28-33.  Back to cited text no. 4
    
5.
Nan X, Xie C, Yu X, Liu J. EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Oncotarget 2017;8:75712-26.  Back to cited text no. 5
    
6.
Wu L, Ke L, Zhang Z, Yu J, Meng X. Development of EGFR TKIs and options to manage resistance of third-generation EGFR TKI Osimertinib: Conventional ways and immune checkpoint inhibitors. Front Oncol 2020;10:602762.  Back to cited text no. 6
    
7.
Chinese Society of Lung Cancer, Chinese Anti-Cancer Association. [EGFR-TKI ADR management Chinese expert consensus]. Zhongguo Fei Ai Za Zhi 2019;22:57-81.  Back to cited text no. 7
    
8.
Mariachiara M, Celeste R, Federico F, Nicole B, Antonio C. Choroidal metastasis from non-small-cell lung cancer responsive to Osimertinib: A case report: Efficacy of a third-generation epidermal growth factor tyrosine kinase inhibitor. Int Ophthalmol 2018;38:2669-75.  Back to cited text no. 8
    
9.
Keshwani K, Roelofs KA, Hay G, Lewis R, Plowman N. Treating choroidal metastases and improving vision with Osimertinib in EGFR T790M-mutated lung adenocarcinoma: A case report and review of the literature. Ocul Oncol Pathol 2021;7:26-30.  Back to cited text no. 9
    
10.
Chen KJ, Chao AN, Wang CL. Iris metastasis regression following Osimertinib treatment. JAMA Ophthalmol 2020;138:e202095.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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