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Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab.

ABSTRACT: Nivolumab improves the prognosis of non-small cell lung cancer (NSCLC) but can cause immune-related adverse events (irAEs). Reports have indicated longer progression-free survivals (PFSs) in patients with irAEs than in those without irAEs. We reported associations between programmed death ligand-1 (PD-L1) single nucleotide polymorphisms (SNPs) and PFS after nivolumab treatment. We hypothesized that adverse events might be associated with the SNPs of PD-L1. We analyzed data from 111 patients with NSCLC treated with nivolumab. The response rate was 14%, and the median PFS was 68 days. We found patients with the adverse event of low free tetraiodothyronine (fT4) had significantly longer PFSs than those without low fT4 (not reached vs 67 days; hazard ratio [HR], 0.297; P?=?0.010). Moreover, median overall survival was longer in patients with low fT4 than those without low fT4 (not reached vs 556 days, HR, 0.139; P?=?0.020). Patients with the T allele of rs1411262 (P?=?0.0073) and with the A allele of rs822339 (P?=?0.0204) developed low fT4. Patients with the T/T genotype had longer PFSs than with those with the C/T and C/C genotypes of rs1411262 (165 vs. 67 days, HR, 1.65; P?=?0.040), and those with the A/A genotype had longer PFSs than those with the A/G and G/G genotypes of rs822339 (182 vs. 67 days, HR, 1.76; P?=?0.025). In the patients with advanced NSCLC, low fT4 after nivolumab treatment was associated with significantly longer PFSs. The SNPs of PD-L1 may be associated with the adverse events of nivolumab.

SUBMITTER: Funazo TY

PROVIDER: S-EPMC6864095 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab.

Funazo Tomoko Yamamoto TY Nomizo Takashi T Ozasa Hiroaki H Tsuji Takahiro T Yasuda Yuto Y Yoshida Hironori H Sakamori Yuichi Y Nagai Hiroki H Hirai Toyohiro T Kim Young Hak YH

Scientific reports 20191119 1

Nivolumab improves the prognosis of non-small cell lung cancer (NSCLC) but can cause immune-related adverse events (irAEs). Reports have indicated longer progression-free survivals (PFSs) in patients with irAEs than in those without irAEs. We reported associations between programmed death ligand-1 (PD-L1) single nucleotide polymorphisms (SNPs) and PFS after nivolumab treatment. We hypothesized that adverse events might be associated with the SNPs of PD-L1. We analyzed data from 111 patients with ...[more]

PMID: 31745135

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Project description:Importance:Nivolumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents. Objective:To determine whether nivolumab increases EGFR-TKI-associated interstitial pneumonitis (IP). Design, Setting, and Participants:A database study of 20 516 participants with NSCLC in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, performed between April 2015 and March 2017. Main Outcomes and Measures:We compared the incidence of EGFR-TKI-associated IP in patients receiving and not receiving nivolumab treatment. Results:The mean (SD) age of participants treated with EGFR-TKI, with and without nivolumab, was 64.4 (15.5) and 68.9 (11.8) years, respectively, and the proportion of men was 40.0% and 53.8%, respectively. Of the 20 516 participants with NSCLC, 985 cases (4.80%; 95% CI, 4.51-5.10) developed IP. Of 5777 patients treated with EGFR-TKI, 265 developed IP (4.59%; 95% CI, 4.06-5.16). Of 70 patients treated with both EGFR-TKI and nivolumab, 18 developed IP (25.7%; 95% CI, 16.0-37.6). The adjusted odds ratio for an interaction between EGFR-TKI and nivolumab was 4.31 (95% CI, 2.37-7.86; P < .001), suggesting the existence of an interaction. When we further stratified the patients by treatment with and without nivolumab, the odds ratio of EGFR-TKI-associated IP in cases with and without nivolumab treatment was 5.09 (95% CI, 2.87-9.03) and 1.22 (95% CI, 1.00-1.47), respectively. Conclusions and Relevance:We found a higher proportion of reports of IP for nivolumab in combination with EGFR-TKI vs treatment with either drug alone. Owing to the limitations of this study, the results warrant further confirmation. However, careful consideration should be given to the possibility of an increased risk of IP when EGFR-TKI is administered in combination with nivolumab, including concomitant and sequential use, and careful monitoring for IP is recommended.

Project description:ImportanceEvidence regarding real-world effectiveness of therapies for patients with advanced non-small cell lung cancer (NSCLC) whose tumors are resistant to platinum-based chemotherapy is lacking.ObjectiveTo compare the effectiveness of the immune checkpoint inhibitors atezolizumab (programmed cell death ligand 1 inhibitor) and nivolumab (programmed cell death 1 inhibitor) and the chemotherapy drug docetaxel in patients with advanced NSCLC resistant to platinum-based chemotherapy.Design, setting, and participantsThis comparative effectiveness study compared patients aged 18 years or older with advanced NSCLC who initiated atezolizumab, docetaxel, or nivolumab and who had previously been exposed to platinum-based chemotherapy using nationally representative real-world data from more than 280 US cancer clinics. Patients were followed-up from May 2011 to March 2020. Data analysis was performed between April and June 2021. Comparisons of interest were between atezolizumab vs docetaxel and atezolizumab vs nivolumab.ExposuresInitiation of atezolizumab, nivolumab, or docetaxel monotherapy.Main outcome and measuresThe main outcome was overall survival (OS).ResultsA total of 3336 patients (mean [SD] age, 67.1 [9.49] years; 1820 [54.6%] men and 1516 [45.4%] women) were assessed in the main analysis, including 206 patients receiving atezolizumab, 500 receiving docetaxel, and 2630 receiving nivolumab. Patients receiving atezolizumab were older than those treated with docetaxel (mean age [SD], 68.3 [9.4] years vs 65.6 [9.5] years), and were more likely to have been treated in an academic setting (39 patients [18.9%]) than those receiving docetaxel (49 patients [9.8%]) and nivolumab (128 patients [4.9%]). After adjustment for baseline characteristics, atezolizumab was associated with a significantly longer OS compared with docetaxel (adjusted hazard ratio [aHR], 0.79; 95% CI, 0.64-0.97). No significant difference in OS was observed between atezolizumab and nivolumab (aHR, 1.07; 95% CI, 0.89-1.28). These findings were consistent across all patient subgroups tested, and robust to plausible deviations from random missingness for Eastern Cooperative Oncology Group performance status in real-world data (eg, the tipping point for loss of a significantly beneficial effect for atezolizumab vs docetaxel was achieved if patients in the docetaxel group missing baseline Eastern Cooperative Oncology Group performance status had a mean performance status of 1.43 higher than expected).Conclusions and relevanceIn this comparative effectiveness study, atezolizumab was superior to docetaxel and matched nivolumab in prolonging OS in a real-world cohort of patients with advanced NSCLC who previously received platinum-based chemotherapy.

Project description:BACKGROUND AND OBJECTIVE:The economic assessment of immuno-oncology agents in Chinese patients is limited despite a need for new therapies. Nivolumab is the first immune checkpoint inhibitor approved for the second-line treatment of non-small cell lung cancer (NSCLC) in China, and it significantly prolongs overall survival. However, considering the high cost of nivolumab, it is urgent to assess its value in China in terms of both efficacy and cost. The objective of this study was to investigate the cost-effectiveness of nivolumab vs docetaxel in the second-line setting for NSCLC patients from the Chinese healthcare system perspective. METHODS:A Markov model consisting of three health states, was designed to evaluate the lifetime cost and effectiveness of nivolumab vs docetaxel in the second-line treatment of NSCLC patients. Clinical data was derived from the CheckMate 078 phase III clinical trial, which included 504 patients predominantly from China. Parametric survival models to fit and extrapolate survival data were chosen based on clinical rationality, visual fit and statistical goodness-of-fit. Lifetime costs and health outcomes were calculated, and US$28,899 and $63,564 per quality-adjusted life-year (QALY) were selected as the willingness-to-pay (WTP) threshold values for general regions and affluent regions, respectively. One-way and probabilistic sensitivity analyses were undertaken to explore the robustness of the model. Additional subgroup analyses were performed. RESULTS:In base case analysis, Nivolumab yielded an additional 0.24 QALYs, at a cost of $93,307 per QALY. Sensitivity analyses suggested that the results to be most sensitive to the price of nivolumab per kg (mean $60.00; range $26.00-$60.00) and the mean patient weight (65 kg, range 52-78 kg). Utility values in progression-free survival state (mean 0.804; range 0.643-0.965) and overall survival hazard ratio (0.68; 97.7% CI 0.52-0.90) had moderate impact on the model results. Subgroup analyses indicated that nivolumab was most cost-effective for patients who were 65 years of age or older ($85,171/QALY), followed by female patients ($85,273/QALY) and patients with tumor PD-L1 expression at least 1% ($90,309/QALY). CONCLUSIONS:Nivolumab is unlikely to be cost-effective compared with docetaxel for patients with previously treated advanced NSCLC in China. Ensuring that nivolumab is included in the National Reimbursement Drug List (NRDL) may be a valid mean of meeting extensive treatment demands in China.

Dataset Information

Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab.

Publications

Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab.

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