Efficacy of pembrolizumab for patients with both high PD-L1 expression and an MET exon 14 skipping mutation: A case report

Abstract

Pembrolizumab has become the standard first-line treatment for non-small cell lung cancer (NSCLC) patients with high PD-L1expression. MET exon 14 skipping is a rare mutation typically found in older, female, and non-smoking patients with NSCLC. Herein, we report the case of a 71-year-old non-smoking woman who was diagnosed with NSCLC in the left lung. EGFR mutation and ALK fusion were not detected. Because the biopsy specimen showed high PD-L1 expression with a tumor proportion score of 95%, pembrolizumab was introduced as first-line therapy, but resulted in no clinical benefit. The patient was subsequently administered chemotherapy with carboplatin and pemetrexed, leading to remarkable tumor shrinkage. A next-generation sequencing panel analysis revealed a MET exon 14 skipping mutation. Thus, pembrolizumab might not be effective for NSCLC patients with MET exon 14 skipping mutations, even if PD-L1 expression is high.

Keywords: MET exon 14 skipping mutation; non-small cell lung cancer; pembrolizumab; pemetrexed; programmed death-ligand 1.

Figure 1

(a) Chest X‐ray on the first visit to our hospital showing a tumor in the left lower lung. (b–d) Computed tomography (CT) of the chest revealed a tumor (30 mm in diameter) in the left S6 with enlargement of the lymph nodes in the hilar and peritracheal regions, as well as a small pulmonary metastasis.

Figure 2

Histopathology of the tumor, showing tumor cells were medium sized and had a polygonal shape with medium cytoplasm and hyperchromatic nuclei (hematoxylin and eosin stain, x20).

Figure 3

(a) Chest X‐ray performed after 38 days of pembrolizumab treatment showing tumor growth and the development of obstructive atelectasis. (b,c) Computed tomography (CT) scan taken on day 25 after the introduction of pembrolizumab, showing that the tumor had increased in size. The patient was re‐hospitalized that day because of dyspnea and acute respiratory failure. (d) Chest X‐ray taken after 19 days of carboplatin and pemetrexed treatment, showing significant reduction of the tumor in the left lung and recovery of the atelectasis. (e,f) A CT scan performed after 43 days of carboplatin and pemetrexed treatment showing further reduction of the tumor in the left lung.