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  • 1
    In: Asia-Pacific Journal of Clinical Oncology, Wiley, Vol. 17, No. 2 ( 2021-04)
    Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced non‐small‐cell lung cancer (NSCLC), yet many patients do not benefit from Programmed cell death protein 1 (PD‐1) axis inhibitors, emphasizing the need for additional markers for better patient selection. Our aim was to evaluate the association between tumor volume and response to ICI. Methods This retrospective ethically‐approved study included all consecutive patients with advanced NSCLC who were evaluated with a fluorodeoxyglucose‐positron emission tomography scan, prior to the first administration of a single‐agent ICI between 1/2016 and 6/2017. Tumor burden was calculated based on total body metabolic tumor volume and sum of all measurable lesions (SOML). Results Median SOML was 88 mm, and was inversely and significantly associated with progression‐free survival (PFS) (hazard ratio [HR] 2, CI 1.28‐3.37, P  = .003) and overall survival (OS) (HR 2.36, CI 1.13‐4.94, P  = .02). SOML≤80 mm had a significantly longer PFS compared to patients with a SOML≥80 mm (median PFS 9.7 vs 3.7 months, respectively, HR for progression 2.26, CI 1.1‐4.5, P  = .02). Patients with a SOML≤80 also had longer median OS compared to patients with SOML≥80 (median OS 12 vs 9.8 months, respectively, HR for death 3.1, CI 1.2‐8, P  = .018). Conclusions Low tumor burden was associated with higher response rates (RR), and better PFS and OS in advanced NSCLC patients treated with ICI. These results may improve the selection of patients for treatment with single‐agent ICI, as opposed to the combination with chemotherapy, which might be more appropriate for patients with high tumor burden. Prospective analysis is warranted.
    Type of Medium: Online Resource
    ISSN: 1743-7555 , 1743-7563
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2187409-8
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  • 2
    In: Oncology, S. Karger AG, Vol. 99, No. 9 ( 2021), p. 555-561
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, 〈 i 〉 t 〈 /i 〉 tests, and χ 〈 sup 〉 2 〈 /sup 〉 tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], 〈 i 〉 p 〈 /i 〉 = 0.011, and HR 1.5 [1.08–2.08], 〈 i 〉 p 〈 /i 〉 = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], 〈 i 〉 p 〈 /i 〉 = 0.79, and HR 1.29 [0.69–2.39], 〈 i 〉 p 〈 /i 〉 = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 3
    In: Thoracic Cancer, Wiley, Vol. 14, No. 17 ( 2023-06), p. 1589-1596
    Abstract: Mutations in genes involved in DNA damage repair (DDR), a hallmark of cancer, are associated with increased cancer cell sensitivity to certain therapies. This study sought to evaluate the association of DDR pathogenic variants with treatment efficacy in patients with advanced non‐small cell lung cancer (NSCLC). Methods A retrospective cohort of consecutive patients with advanced NSCLC attending a tertiary medical center who underwent next‐generation sequencing in 01/2015‐8/2020 were clustered according to DDR gene status and compared for overall response rate (ORR), progression‐free survival (PFS) (patients receiving systemic therapy), local PFS (patients receiving definitive radiotherapy), and overall survival (OS) using log‐rank and Cox regression analyses. Results Of 225 patients with a clear tumor status, 42 had a pathogenic/likely pathogenic DDR variant (pDDR), and 183 had no DDR variant (wtDDR). Overall survival was similar in the two groups (24.2 vs. 23.1 months, p  = 0.63). The pDDR group had a higher median local PFS after radiotherapy (median 45 months vs. 9.9 months, respectively; p  = 0.044), a higher ORR (88.9% vs. 36.2%, p  = 0.04), and a longer median PFS (not reached vs. 6.0 months, p  = 0.01) in patients treated with immune checkpoint blockade. There was no difference in ORR, median PFS, and median OS in patients treated with platinum‐based chemotherapy. Conclusion Our retrospective data suggest that in patients with stage 4 NSCLC, pathogenic variants in DDR pathway genes may be associated with higher efficacy of radiotherapy and immune checkpoint inhibitors (ICIs). This should be further explored prospectively.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2559245-2
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