Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice

Abstract

Purpose Immune checkpoint inhibitors (ICI) have shown marked responses in patients with non-small cell lung cancer (NSCLC) in clinical trials. However, because such trials comprise cohorts selected based on specific criteria, it is unclear if their results represent routine clinical practice. Methods We examined 155 patients with advanced NSCLC who were administered either nivolumab or pembrolizumab at Yonsei Cancer Center, Korea between March 2014 and January 2019. Patient characteristics, EGFR / ALK mutation status, metastatic locations, response to ICIs, and adverse events were retrospectively analyzed. Results The median age was 64 years and 72.9% of patients were male; former or current smokers constituted 67.1% of the subjects. Adenocarcinoma was predominant (67.7%), and 50.3% of the patients underwent ≥ 2 previous treatments. Twenty-three patients (14.8%) were EGFR mutation- or ALK rearrangement-positive. The objective response rate (ORR) was 23.9% [95% confidence interval (CI) 17.4–31.4%]; the median progression-free survival (PFS) and overall survival (OS) were 3.06 (95% CI 1.893–4.21) and 10.25 (95% CI 5.39–15.11) months, respectively. Multivariate analysis identified ECOG performance status, EGFR mutation/ ALK rearrangement status, liver metastasis and PD-L1 proportion as independent predictors of OS. Furthermore, 61.9% of the patients had adverse events of any grade; 38.1% had immune-related adverse events that were associated with PFS and OS on multivariate analysis. Conclusions The real-world ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials despite the patients’ different baseline characteristics. Our findings can aid in establishing effective immunotherapeutic management of NSCLC in routine clinical practice. Electronic supplementary material The online version of this article (10.1007/s00432-019-02899-y) contains supplementary material, which is available to authorized users.

Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis

“…Conventional treatment of liver metastases consists of systematic and palliative therapy (39). With the advent of immunotherapy with revolutionary efficacy, however, several studies have demonstrated liver metastases as an independent poor prognostic factor of immunotherapy for NSCLC (11)(12)(13). Patients with liver metastases exhibited significantly shorter OS (mOS, 3.12 months) and PFS (mPFS, 1.35 months) compared with those without liver metastases (mOS, 11.37 months; mPFS, 3.75 months) in a retrospective study, with an overall response rate (ORR) of 22.5% (40).…”

“…In a real-world cohort investigating the efficacy of nivolumab in patients with NSCLC, the presence of liver metastases predicted worse overall survival (4.0 vs. 9.0 months, p < 0.001), while pulmonary metastasis conferred a better outcome (8.8 vs. 5.6 months, p = 0.004) (10). Among different metastatic sites, bone, brain, and liver metastases were generally regarded as independent poor prognostic factors for ICI therapies (11)(12)(13)(14). However, these results did not compare the efficacy of ICIs with other conventional treatments.…”

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

“…A number of recent studies has supported this hypothesis by showing favorable outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma who developed various irAEs in response to immune checkpoint inhibition [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, a definite conclusion has not been drawn based on the findings from each single study, as contradictory results exist [23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer

“…Remarkably, monoclonal antibodies such as pembrolizumab and nivolumab targeting the programmed death 1 (PD-1) receptor and its ligand programmed death-ligand 1 (PD-L1), facilitate a patient’s own T cells to kill tumors, resulting in remarkable antitumor activity in NSCLC patients 5 , 6 . Recent clinical trials 7 – 11 and real-world data 12 – 14 have shown that anti-PD-1/PD-L1 immunotherapy results in robust disease control, long-term survival, and improved quality of life in advanced NSCLC patients. Unfortunately, immunotherapy can only benefit a subgroup of patients, and demonstrates response rates of only 17%–21% 15 .…”