Fatal toxic effects related to EGFR tyrosine kinase inhibitors based on 53 cohorts with 9,569 participants.

BACKGROUND: To estimate the incidence and susceptible factors of fatal toxic effects related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). METHODS: PubMed and Embase were thoroughly searched for clinical trials based on the following terms and corresponding Medical Subject Heading ones: "erlotinib", "gefitinib", "afatinib", "dacomitinib", "osimertinib", and "non-small-cell lung cancer (NSCLC)". A total of 53 eligible cohorts with 9,569 participants were collected. RESULTS: A total of 105 cases of fatal toxic effects related to EGFR-TKIs occurred in 53 cohorts. The overall incidence was 1.33% [95% confidence interval (CI): 1.08-1.63%]. The odds and incidence were apparently higher in Japanese group (compared with non-East Asian group) [2.72 vs. 1.30, P=0.015; odds ratio (OR): 2.26, 95% CI: 1.17-4.37, P=0.015], in first-line treatment group (compared with EGFR-TKI retreatment group) (1.54 vs. 0.69, P=0.028; OR: 2.41, 95% CI: 1.10-5.26, P=0.028), and in the trial phase II (compared with trial phase III) (1.82% vs. 1.11%, P=0.009; OR: 1.73, 95% CI: 1.15-2.62, P=0.009). Notably, the Japanese group was higher than non-East Asian group after controlling for the treatment-line and trial phase (OR: 2.16, 95% CI: 1.12-4.16, P=0.022). Interstitial lung disease (ILD) was predominant in 29 fatal causes followed by pneumonia, respiratory failure and diarrhea. CONCLUSIONS: The overall incidence of fatal toxic effects related to EGFR-TKIs was 1.33%, and the major fatal cause was ILD, followed by pneumonia, respiratory failure and diarrhea. The susceptible factor of fatal toxic effects related to EGFR-TKIs was the Japanese group. This study provided a capability for clinicians to predict and detect high-risk populations of fatal toxic effects.

Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio in Outcome of Immune Checkpoint Inhibitors.

A meta-analysis of 14 studies (16 cohorts) incorporating 1751 participants was performed to evaluate the correlation between baseline neutrophil-to-lymphocyte ratio (NLR) and outcome of immune checkpoint inhibitors (ICI). The pooled hazard ratio (HR) suggested elevated pretreatment NLR was associated with poor OS (HR: 2.61, 95% confidence intervals (CI): 1.77-3.86, p < 0.00001) and PFS (HR: 1.74, 95% CI: 1.34-2.27, p < 0.0001). Stratified analyses on tumor types, ICI agents, the cutoff value of NLR and study regions exhibited the similar outcomes. This study demonstrated that elevated NLR was a predictor of poor OS and PFS for ICI.

Predictive value of positron emission tomography for the prognosis of molecularly targeted therapy in solid tumors.

OBJECTIVE: This study aimed at comprehensively exploring the value applying positron emission tomography (PET) to predict the effect of molecularly targeted therapy in solid tumors. MATERIALS AND METHODS: A systematic search was performed for potentially relevant studies from the time of inception to February 2017. The primary endpoints were progression-free survival (PFS), overall survival (OS), and time to progression (TTP). The results were analyzed by Review Manager version 5.3 (RevMan 5.3) statistical software. Subgroup analyses were implemented based on the type of molecularly targeted agents (monoclonal antibodies arm and small molecular targeted agents arm), mechanism (erlotinib/gefitinib arm and bevacizumab arm), radioactive tracers, type of tumor, and reevaluated PET timing. RESULTS: Twenty-six studies incorporating 865 individuals were eligible. Compared with PET nonresponse group, PET response group displayed a decrease in maximal standard uptake value (SUVmax), which was associated with a significantly prolonged PFS (HR =0.41, 95% CI [0.29, 0.59]; P<0.00001), OS (HR =0.52, 95% CI [0.40, 0.67]; P<0.00001), and TTP (HR =0.30, 95% CI [0.14, 0.66]; P=0.003). Similar results were obtained in the subgroup analyses of PFS in erlotinib/gefitinib arm and small molecular targeted agents arm; and OS in lung cancer arm, erlotinib/gefitinib arm, bevacizumab arm, small molecular targeted agents arm, monoclonal antibodies arm, 18F-fluorodeoxythymidine (18F-FLT) arm, 18F-fluorodeoxyglucose (18F-FDG) arm, and early PET timing arm. CONCLUSION: Our study demonstrated that PET was a favorable approach to predict the prognosis of molecularly targeted therapy for solid tumors. PET assessment within 2 weeks could be useful to predict clinical outcome.