Osimertinib Induced Rapid Regression of Large Metastatic Tumor to the Pituitary in a Patient with Lung Adenocarcinoma

 

Introduction: Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) approved for treatment of non-small cell lung cancer (NSCLC) harboring an epithelial growth factor receptor (EGFR) mutation. Metastatic NSCLC to the pituitary (NSCLC-PitM) presents unique challenges, as treatment paradigms must balance local mass effect with systemic disease. Surgical intervention has been prioritized when clinical evidence of mass effect on optic nerves and chiasm are present for fear of worsening or irreversible damage. We present a case of a NSCLC-PitM with significant compression of the optic chiasm that was treated with osimertinib resulting in complete regression of pituitary tumor burden in four weeks and resolution of symptoms.

Case Description: A 43-year-old male nonsmoker presented with pleuritic chest pain and decreased vision. Chest CT revealed a right upper lobe lung mass with biopsy consistent with NSCLC. Molecular testing demonstrated EGFR exon-19 deletion. MRI brain revealed a large sellar and suprasellar mass with compression of the optic chiasm ([Fig. 1A and B]). Ophthalmologic evaluation demonstrated associated visual field deficit ([Fig. 2A and B]).

Multidisciplinary discussion considered the differential diagnosis of pituitary macroadenoma versus NSCLC-PitM. The patient was initiated on osimertinib therapy with a plan for close monitoring of symptomatic worsening and re-imaging at 4 to 6 weeks to evaluate for response and surgical resection of the pituitary lesion at that time if necessary.

MRI at 4 weeks after osimertinib initiation demonstrated complete resolution of the pituitary lesion ([Fig. 1C and D]). Repeat visual field testing found improvement in the previous deficit ([Fig. 2C and D]).

Discussion: In individuals with NSCLC containing mutations in the gene coding for EGFR, EGFR-TKIs are able to block cellular signal cascades from initiating. Osimertinib is a third-generation EGFR-TKI that has shown improved survival as a first line treatment over first- and second-generation EGFR-TKIs and as second-line treatment when resistance to first- and second-generation EGFR-TKIs develops. Importantly, this benefit extended to those with central nervous system involvement as well. Despite this, the local effects of NSCLC-PitM can make its treatment challenging with 49% of patients with NSCLC-PitM presenting with visual symptoms. Surgical decompression has been favored over systemic therapy over fears of irreversible deficits caused by continued local mass effect. As a result, little is known about NSCLC-PitM's response to EGFR-TKIs and, in particular, visual outcomes. In this case, by initiating EGFR-TKI therapy, we were able to address his systemic disease and potentially the pituitary lesion. Should the pituitary lesion be an adenoma, early initiation of therapy, and reduction of systemic tumor burden potentially minimizes perioperative morbidity for subsequent resection. On the other hand, if it is an NSCLC-PitM, which it ultimately proved to be, it may be treated concomitantly obviating the need for surgical intervention. While limited to one case, this report may serve as a framework for treating patients with EGFR-mutated NSCLC-PitM who present with optic nerve or chiasm compression and visual symptoms. We believe that it is reasonable to initiate EGFR-TKIs with close monitoring for progression of symptoms and follow-up imaging at 4 weeks.

Publication History

Article published online:
12 February 2021

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