Analysis Of Efficacy And Prognosis Of Immune Checkpoint Inhibitors In Patient With Driver-negative Advanced Non-small Cell Lung Cancer After Previous Systemic Treatment Failure

Objective: To evaluate the efficacy and prognosis of Immune checkpoint inhibitors in patients with driver-negative advanced non-small cell lung cancer after previous systemic treatment failure,and to explore the optimal strategy of posterior line immunotherapy and the dominant population.Methods: We retrospectively analyzed the efficacy of patients with driver-negative advanced non-small cell lung cancer after previous systemic treatment failure who received immunotherapy and visited the First Affiliated Hospital of China Medical University from January 2018 to December 2022.Clinicopathological characteristics,treatment information,and survival information were collected from the patients,and differences between groups in categorical variables were analyzed by chi-square test and logistic regression.Survival curves were plotted using the Kaplan-Meier method and compared by the Log-Rank test,variables identified in univariate analysis(P < 0.20)were included in Cox proportional hazards regression models,and multivariate analysis identified independent predictors(P < 0.05).Finally,Nomogram models are constructed and evaluated.Results: A total of 149 patients were included,with a median follow-up time of 22.03(3.73-57.40)months.The overall response rate(ORR)and disease control rate(DCR)were 27.1% and 70.0% respectively.Median progression-free survival(PFS)was 6.10months(95%CI: 4.69-7.51)and median overall survival(OS)was 23.30 months(17.03-28.76).Binary logistic regression analysis suggested that patients who developed immune-related adverse reactions(ir AEs)(41.1% vs 17.9%;P = 0.017)and increased lymphocyte-monocyte ratio(LMR)after 2 cycles of treatment(38.9% vs 16.9%;P =0.032)had a higher ORR.Immunochemotherapy(78.9% vs.56.4%;P<0.001),ir AEs(87.5% vs.58.3%;P < 0.001),family history of malignancy(78.3% vs.66.0%;P=0.046),GGT decreased after two cycles of treatment(79.0% vs.61.8%;P=0.009)showed significant improvement in DCR.Multivariate COX regression analysis showed that immunochemotherapy(HR=0.464,95%CI: 0.276-0.779;P=0.004),no bone metastasis(HR=0.597,95%CI:0.370-0.962;P=0.034),ir AEs(HR=0.508,95%CI:0.328-0.788;P=0.002),low baseline GGT level(HR=0.556,95%CI:0.347-0.890;P=0.015),and elevated LMR after 2 cycles of treatment(HR=0.491,95%CI:0.297-0.813;P=0.006)were independent predictors of PFS prolongation in patients with driver-negative treatment-experienced advanced non-small cell lung cancer receiving immunotherapy.No liver metastasis(HR=0.408,95%CI:0.207-0.804;P=0.010),low baseline ANC level(HR=0.415,95%CI: 0.66-0.833;P=0.013),low baseline GGT level(HR=0.411,95%CI:0.232-0.727;P=0.002),decreased ANC(HR=0.486,95%CI:0.268-0.883;P=0.018)and increased LMR(HR=0.548,95%CI:0.321-0.935;P=0.027)after 2 cycles of treatment were independent predictors of OS prolongation.Finally,Nomogram models were constructed to predict progression-free survival at 3 months,6 months and 12 months,and survival at 1 year,1.5 years,2 years,and calibration curves were drawn.The results indicated that both models had good predictive efficacy.Conclusions: Patients with low baseline GGT levels had higher ORR and DCR,and lower GGT levels after 2 cycles of treatment were significantly associated with improvements in DCR.Immunochemotherapy,absence of bone metastasis,occurrence of ir AEs,low baseline GGT level,and increased LMR after 2 cycles of treatment were independent predictors of prolonged PFS in patients with driver-negative advanced non-small cell lung cancer after previous systemic treatment failure.No liver metastasis,low baseline ANC level,low baseline GGT level,reduced ANC and elevated LMR after2 cycles of treatment were independent predictors of prolonged OS.