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      Association of PD-L1 expression and clinical outcomes in ROS1 - rearranged advanced non-small cell lung cancer treated with crizotinib

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          Abstract

          Background

          Programmed cell death ligand 1 (PD-L1) is more readily expressed in ROS proto-oncogene 1 (ROS1) rearranged non-small cell lung cancer (NSCLC) compared to NSCLC cases lacking driver gene mutations. Prior research has established a link between PD-L1 expression and reduced effectiveness of EGFR or ALK inhibitors in EGFR or ALK-positive NSCLC. Nonetheless, the relationship between initial PD-L1 levels and the clinical impact of first-line crizotinib therapy in ROS1-rearranged NSCLC is still uncertain.

          Methods

          From January 2016 to December 2021, a total of 246 patients with ROS1 positive tumors were collected. Out of these, 82 patients with advanced ROS1-rearranged NSCLC, who were treated with crizotinib as their initial therapy, were selected for the study. The study aimed primarily to evaluate the objective response rate (ORR) and progression-free survival (PFS), and secondarily to assess disease control rate (DCR) and overall survival (OS).

          Results

          Of the 82 advanced ROS1-rearranged NSCLC patients, 38 exhibited PD-L1 positivity, subdivided into 11 with high and 27 with low expression levels, while the remaining 44 showed no PD-L1 expression. The ORR for all included patients was 80.5%. No statistically significant variance in ORR was observed among ROS1-rearranged NSCLC patients across differing PD-L1 expression statuses. However, there was a statistically significant difference in DCR between PD-L1 negative group (100%) and high expression group (90.9%) (p=0.04). The median PFS spanned 26.4 months for the PD-L1 negative group, 16.6 for the low expression group, and 13.7 for the high expression group (p=0.001). Additionally, a notable statistical disparity was also observed in median PFS between the PD-L1 negative and positive groups (p=0.02). For the entire study population, the median OS was 53.0 months (95% CI 43.8 - 62.2). In the PD-L1-negative group, the median OS reached 57.2 months, compared to 53.0 months in the PD-L1-positive group, a difference lacking statistical significance (p=0.43).

          Conclusions

          Our results suggest that for ROS1-positive NSCLC patients receiving crizotinib as first-line therapy, PD-L1 expression may serve as a negative prognostic marker for PFS rather than OS.

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          Most cited references45

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          Cancer statistics, 2023

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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            Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

            Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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              Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer

              Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2692820Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1963948Role: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1411636Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role: Role: Role: Role:
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                21 May 2024
                2024
                : 14
                : 1405683
                Affiliations
                [1] 1 Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, China
                [2] 2 Department of Emergency Medicine, The Fifth Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, China
                Author notes

                Edited by: Myrto K. Moutafi, University General Hospital Attikon, Greece

                Reviewed by: Evangelos Zazas, University General Hospital Attikon, Greece

                Anastasios Pantazopoulos, University General Hospital Attikon, Greece

                Georgia Gomatou, National and Kapodistrian University of Athens, Greece

                *Correspondence: Xingya Li, lixingya0905@ 123456vip.163.com ; Ningning Yan, yanningrj@ 123456163.com
                Article
                10.3389/fonc.2024.1405683
                11148223
                38835380
                600a544a-10ca-49ba-9157-f0d35780c105
                Copyright © 2024 Zhang, Zhang, Yan and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 March 2024
                : 30 April 2024
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 45, Pages: 9, Words: 3921
                Funding
                Funded by: Henan Provincial Science and Technology Research Project , doi 10.13039/501100017700;
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by a grant of the Henan Provincial Science and Technology Research Project (Grant N. 2008020081).
                Categories
                Oncology
                Original Research
                Custom metadata
                Thoracic Oncology

                Oncology & Radiotherapy
                pd-l1,clinical outcomes,ros1,nsclc,crizotinib
                Oncology & Radiotherapy
                pd-l1, clinical outcomes, ros1, nsclc, crizotinib

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