Pembrolizumab in a Patient with Treatment-Naïve Unresectable
A 69-year-old male presented with a 2-month history of dysphagia, dysphonia, pain in the right neck and right ear, and a ten-pound weight loss. Thyroid function tests were normal. A physical examination revealed a large, right-sided neck mass. Confirmed by a neck ultrasound, the mass was hypoechoic with macrocalcification and ill-defined borders measuring at least 5.5 cm. A fine-needle aspiration (FNA) biopsy at an outside institution revealed malignancy best classified as primary thyroid cancer with high grade and spindle cell origin with suspicion of anaplastic thyroid cancer (ATC). The patient was then referred to our institution for further management. Laryngoscopy revealed right vocal cord paralysis. A CT scan of the neck showed a large, right thyroid lobe mass measuring 7.5×4.1 cm, displacing the larynx and trachea to the left and encasing the internal carotid artery by at least 180°.

A repeat FNA biopsy of the right thyroid mass revealed discohesive atypical pleomorphic tumor cells consistent with ATC (Figure 3). Immunocytochemistry staining of both FNA samples was focally positive for TTF 1, variably positive for thyroglobulin and PAX8, and negative for calcitonin, CEA, SOX-10, and p63. PD-L1 22C3 pharmDx—performed on Dako Autostainer Link 48—was positive for high PD-L1 expression with tumor proportion score (TPS). Molecular testing of the tumor was negative for BRAF (V600/601), KRAS (Exon 2/3/4), and NRAS mutations. Next-generation sequencing of the tumor could not be done due to inadequate tissue. Liquid biopsy revealed no reportable genomic alterations. However, this was performed while the patient was on pembrolizumab treatment and not before its initiation. The tumor was deemed unresectable, and the patient declined chemotherapy and radiation therapy. Given the high PD-L1 expression, off-label intravenous pembrolizumab at 200 mg every three weeks was initiated with patient consent and the absence of a clinical trial accessible to the patient.

One week after the first dose, the patient had significant improvement in dysphagia and resolution of pain in the right neck and ear. Restaging scans after four cycles of treatment (one cycle equaling three weeks) revealed a partial response per RECIST v 1.1 (48% decrease in the size of the tumor). He continues to tolerate the treatment well without adverse events, except for the development of immune-mediated thyroiditis. After an initial thyrotoxic phase, the thyroiditis has progressed toward persistent hypothyroidism and has required thyroid hormone replacement therapy. The patient has received 25 doses of pembrolizumab with continued reduction in the size of the tumor with most recent scans performed showing approximately 66% reduction in tumor from pretherapy. The tumor has become resectable but with remaining significant potential high functional morbidities such as possible laryngopharyngectomy and tracheal and esophageal resection given its location. However, the patient continues to decline surgical therapy.