RESUMO
BACKGROUND: With the current wide use of checkpoint inhibitors in the treatment of solid tumors, some patients who initially respond to immunotherapy have been shown to develop acquired resistance. However, the manifestation and underlying mechanisms are currently poorly understood. This is the first reported case of acquired resistance and pleural metastasis with uncontrolled massive bloody pleural effusion after immunotherapy. CASE DESCRIPTION: Case 1, a 54-year-old man, was treated with erlotinib for advanced lung adenocarcinoma due to deletion mutations in exon 19 of epidermal growth factor receptor (EGFR). After disease progression, he received pembrolizumab. The best efficacy evaluation during the period was partial response (PR). After 12 cycles of treatment, the patient exhibited rapid disease progression characterized by bloody pleural effusion. Pembrolizumab treatment was discontinued and an attempt was made to inject bevacizumab into the chest cavity; however, the bloody pleural effusion remained difficult to control. The patient experienced a rapid disease progression and died. Case 2, a 71-year-old man, with advanced hepatocellular carcinoma who had previously undergone right hepatectomy, and subsequently received pembrolizumab treatment after disease progression. During the treatment period, his best efficacy evaluation also reached PR. After 23 cycles of treatment, he developed a massive bloody pleural effusion in the chest cavity. He continued to use pembrolizumab for 2 cycles, and anti-angiogenic drugs were injected into the chest cavity, while taking lenvatinib orally; however, the bloody pleural effusion remained difficult to control. The patient eventually died of tumor progression. After the emergence of resistance, we subjected the pleural effusion of the 2 patients to next-generation sequencing (NGS), and preliminarily analyzed the relevant biomarkers. CONCLUSIONS: We found fibroblast growth factor (FGF) family gene mutations in pleural fluid obtained from two patients after immunotherapy resistance. It may suggest that the FGF family may be involved in the development of pembrolizumab resistance. And the combination of fibroblast growth factor receptor (FGFR) inhibitors and immune checkpoint inhibitors (ICIs) may be a promising option for cancer patients.
