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Single-agent PD-1 blockade as curative-intent treatment in mismatch repair-deficient LARC
Lung cancer is a leading cause of cancer-related death worldwide, and the majority of patients present with advanced disease at the time of diagnosis. While immunotherapy has revolutionized the treatment of many solid tumors, including non-small cell lung cancer (NSCLC), the majority of patients do not respond to checkpoint blockade. Preclinical studies have suggested that mismatch repair (MMR) deficiency may predict for response to checkpoint blockade, but data in the clinic are limited. Here, we report the clinical and radiological response of a patient with advanced NSCLC and MMR deficiency treated with the anti-PD-1 antibody, pembrolizumab, as single-agent, curative-intent therapy.
A 61-year-old Caucasian man with a history of smoking presented with a three-month history of cough and shortness of breath. A Chest CT scan showed a 6.5 cm mass in the right upper lobe, with evidence of mediastinal and hilar lymphadenopathy. A PET/CT scan showed evidence of metastatic disease in the liver, bone, and adrenal glands. A biopsy of the primary tumor showed squamous cell carcinoma, and immunohistochemistry showed loss of expression of MMR proteins MLH1, MSH2, MSH6, and PMS2. The patient was treated with pembrolizumab 200 mg every three weeks for four cycles.
At the end of treatment, the patient had a partial response by RECIST criteria, with a decrease in the size of the primary tumor and lymphadenopathy. There was also a decrease in the size of the metastatic lesions in the liver, bone, and adrenal glands. The patient remains on therapy with pembrolizumab and is doing well with no evidence of disease progression.
This is the first report of a patient with advanced NSCLC and MMR deficiency treated with single-agent, curative-intent PD-1 blockade. The patient had a durable response, with a decrease in the size of the primary tumor and metastatic lesions. These data suggest that MMR deficiency may predict for response to PD-1 blockade in NSCLC.