A lung adenocarcinoma patient with ROS1 fusion and NBN germline mutation achieves long progression-free survival from sintilimab combined with niraparib after failure of ROS1 inhibitors: a case report

Abstract

Background: Lung cancer is a malignant tumor with high morbidity and mortality worldwide. At present, the main treatment methods for patients with advanced non-small cell lung cancer (NSCLC) include molecular targeted therapy and immunotherapy. The efficacy rate of immune checkpoint inhibitor (ICI) monotherapy is relatively low. Studies have confirmed that some combination therapies have better anti-tumor efficacy and higher response rates, such as PD-1/PD-L1 inhibitors combined with chemotherapy or targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors have become a new line of cancer therapy in ovarian and breast cancer, but it's not approved in lung cancer. Some reports show that homologous recombination repair (HRR) gene variants may be potential biomarkers for immunotherapy. However, whether lung cancer with HRR gene variants can be benefit from ICIs combined with PARP inhibitors is unknown.Case Description: We present a case of a 30-year-old man who was admitted to hospital with several months of cough and the chest computed tomography (CT) scan showed a mass about 2.6 cm × 2.1 cm in the left lung. Then he was diagnosed with lung adenocarcinoma (LUAD). Next generation sequencing (NGS) revealed that he harbors ROS1 fusion and NBN germline mutation. So, he received platinum-based chemotherapy and ROS1 inhibitors, but the disease continued to progress. Ultimately, the patient was switched to sintilimab combined with niraparib and the efficacy was evaluated as stable disease (SD), with a progression-free survival (PFS) of more than 12 months, and the overall survival (OS) is 23 months up to now. During the treatment, the major adverse events (AEs) observed were lymphopenia, nausea, vomiting, and edema. The AEs were tolerable.Conclusions: This case shows that the combination of small-molecule inhibitors and immunotherapy may improve survival in NSCLC patients with driver genes, and sintilimab combined with niraparib provides a successful clinical case for the treatment of refractory tumors HRR gene mutation, which can be used as a reference for personalized treatment. Of course, more clinical trials are needed to confirm this combination treatment strategy.

Efficacy of chemoimmunotherapy in a lung adenocarcinoma patient with mutations in the KRAS and STK11

“…Assumably, combining PARP inhibitors and immunotherapy would be a way to intensify this effect. Such a strategy is being investigated in some patients, and Xu et al [22] described a case of ROS1and NBN-mutated patient with long-term response to an ICI -sintilimab (anti-PD-1 antibody) in combination with PARP inhibitor -niraparib after the failure of ROS1 inhibitor therapy.…”