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Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC.

ABSTRACT: Background:The combination of bevacizumab and chemotherapy is still one of the standard treatments for advanced non-small-cell lung cancer (NSCLC) patients in the new era of targeted therapy. Although a high level of baseline lactate dehydrogenase (LDH) was found to predict survival benefit from bevacizumab in patients with metastatic colorectal cancer, the predictive value of serum level of LDH in NSCLC patients treated with bevacizumab has not been investigated yet. Moreover, dynamic evaluation of serum level of LDH changes may be more informative and promising in predicting patients' prognosis. We thus sought to analyze LDH kinetics and evaluate its predictive role in the response and survival of advanced NSCLC patients treated with bevacizumab. Method:We retrospectively collected and analyzed a total of 161 advanced NSCLC patients who had undergone treatment with bevacizumab. Univariate and multivariate logistic regression analyses of serum level of LDH were used for response analyses, and Cox models for both overall survival (OS) and progression-free survival analyses (PFS). Longitudinal analysis of LDH was performed using a mixed-effect regression model. Results:On multivariate Cox models, increase of serum level of LDH after 4 cycles with bevacizumab (INC4) treatment was shown to be the independent risk factor for OS (hazard ratio =2.17, 95% CI: 1.21-3.90, P=0.009), and the serum level of LDH after 2 cycles (LDH2) and the increase of LDH after 6 cycles with bevacizumab (INC6) treatment were the predictive factors for PFS (hazard ratio =2.33, 95% CI: 1.38-3.93, P=0.001; hazard ratio =1.96, 95% CI: 1.27-3.03, P=0.002, respectively). Patients with increase of serum level of LDH after 2 cycles of treatment with bevacizumab (INC2) (odds ratio =3.75, 95% CI: 1.83-7.68, P<0.001) were more likely to attain stable disease/progressive disease on multivariate logistic regression analyses, while patients with complete response (CR)/partial response (PR) experienced a reduction of serum level of LDH every 2 cycles (Coef =-0.076, std error =0.017, P<0.001) over time. Conclusion:Dynamic changes of LDH were superior to baseline LDH in predicting prognosis of NSCLC patients treated with bevacizumab. Serum level of LDH reducing over time was a potential biomarker for patients to achieve good clinical response (CR/PR) to bevacizumab.

SUBMITTER: Li B

PROVIDER: S-EPMC6166744 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC.

Li Butuo B Li Cheng C Guo Meiying M Shang Shuheng S Li Xiaogang X Xie Peng P Sun Xindong X Yu Jinming J Wang Linlin L

OncoTargets and therapy 20180927

<h4>Background</h4>The combination of bevacizumab and chemotherapy is still one of the standard treatments for advanced non-small-cell lung cancer (NSCLC) patients in the new era of targeted therapy. Although a high level of baseline lactate dehydrogenase (LDH) was found to predict survival benefit from bevacizumab in patients with metastatic colorectal cancer, the predictive value of serum level of LDH in NSCLC patients treated with bevacizumab has not been investigated yet. Moreover, dynamic e ...[more]

PMID: 30310292

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Project description:Previous studies have suggested that a variety of tumor driver genetic alterations affected the treatment efficacy of chemotherapy and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the tumor genetic alteration landscape and the treatment outcome of first-line chemotherapy and EGFR-TKIs in advanced NSCLC. A total of 94 patients with advanced NSCLC were recruited. All patients received first-line chemotherapy and/or EGFR-TKIs (either first- or second-generation EGFR-TKI, or third-generation EGFR-TKI) alone or sequentially. Prior to chemotherapy and/or EGFR-TKI treatment, plasma, effusion and/or tumor tissues from the included patients were subjected to next-generation sequencing, targeting 59 genes. The results indicated that the positive genetic alteration status prior to first-line chemotherapy was associated with prolonged progression-free survival (PFS) time compared with the negative status [9.1 vs. 4.0 months; hazard ratio (HR)=6.68; 95% CI, 2.25-19.82; P=0.001). Furthermore, patients with EGFR activating mutation harboring concomitant alterations exhibited a shorter PFS (11.1 vs. 7.4 months; HR=2.14; 95% CI, 1.03-4.44; P=0.04) and overall survival (OS) time [not reached (NR) vs. 32.8 months; HR=4.30; 95% CI, 1.41-13.16; P=0.01] than those without concomitant alterations, with first- and second-generation EGFR-TKI treatment. Similarly, patients with T79M mutation harboring concomitant alterations exhibited a shorter PFS (15.6 vs. 3.6 months; HR=9.48; 95% CI, 2.29-39.28; P=0.002) and OS time (NR vs. 32.8 months; HR=4.85; 95% CI, 1.16-20.29; P=0.03) with osimertinib treatment. Taken together, the results demonstrated that positive genetic alteration status predicted greater efficacy of first-line chemotherapy, while concomitant genetic alterations were associated with poor treatment outcome for first- or second-generation EGFR-TKI and third-generation EGFR-TKI treatment.

Project description:BackgroundVascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.MethodsUsing a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important.ResultsGroups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan-paclitaxel was not superior to cisplatin-paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P=0.004 in a one-sided test) and higher response rates (48% vs. 36%, P=0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).ConclusionsThe addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.).

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Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC.

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Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC.

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