ABSTRACT
This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‒1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‒2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‒1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‒1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‒0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‒0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‒8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‒6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Extracellular Matrix Proteins/genetics , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Treatment OutcomeABSTRACT
Objective To evaluate the efficacy and safety of solifenacin in the treatment of overactive bladder (OAB) syndrome in patients who have undergone transurethral resection of the prostate (TURP). Methods According to the Overactive Bladder Symptom Score (OABSS), 64 cases with OAB symptoms after TURP were randomly assigned into study and control groups with 32 cases in each group. Patients in the study group were treated with solifenacin (5 mg once daily) for a two week period beginning the first day after catheter removal. Patients in the control group were not treated with solifenacin. The mean urgency episodes, micturition episodes, nocturia, urge incontinence, volume voided per micturition, Qmax and OABSS scores were recorded on the 7th and the 14th day after catheter removal. Treatment-emergent adverse events with solifenacin in the study group were recorded and evaluated as well. All cases were followed-up for 8 weeks after catheter removal. Results There were statistically significant differences (P<0.01) in favor of the study group over the control group in the aspect of urgency, micturition episodes, nocturia, urge incontinence, volume voided per micturition and OABSS scores. The incidences of treatment related adverse events were 12.5% (4/32) in the study group with no serious adverse event observed. Conclusions Solifenacin is effective in the treatment of OAB syndrome after TURP and is well tolerated as well. Application of solifenacin should be recommended earlier after TURP.