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      Octogenarians with EGFR-mutated non-small cell lung cancer treated by tyrosine-kinase inhibitor: a multicentric real-world study assessing tolerance and efficacy (OCTOMUT study)

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          Abstract

          Objective

          To assess efficacy and tolerance of EGFR tyrosine-kinase inhibitors (TKIs) for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in octogenarians.

          Patients and methods

          Patients aged 80 years or older with EGFR-mutated NSCLC treated by EGFR TKI between January 2011 and March 2015 whatever the line of treatment were retrospectively selected.

          Results

          20 centers retrospectively included 114 patients (women, 77.2%; Caucasians, 98.3%; mean age, 83.9 years). A performance status of 0–1 or 2–3 at diagnosis was reported for 71.6% and 28.4% of patients, respectively. Overall, 95.6% of patients had adenocarcinomas and histological stage at diagnosis was stage IV for 79.8% of patients. EGFR mutations were identified mainly on exon 19 (46.5%) and exon 21 (40.4%). A geriatric assessment was performed in 35.1% of patients. TKI treatment was administered to 97.3% of patients as first or second line of treatment. Overall response rate and disease control rate were 63.3% (69/109) and 78.9% (86/109), respectively. Median progression-free survival was 11.9 months (95% confidence interval [CI], 8.6–14.7) and median overall survival was 20.9 months (95% CI, 14.3–27.1). After progression, 36/95 (37.9%) patients received a new line of chemotherapy. Main toxicities were cutaneous for 66.7% of patients (grade 3–4, 10%), diarrhea for 56.0% (grade 3–4, 15%; grade 5, 2%) and others for 25.7% (grade 3–4, 41%).

          Conclusions

          Octogenarians with EGFR-mutated NSCLC treated by EGFR TKI had clinical outcomes and toxicity profile comparable to younger patients. Geriatric assessment appeared to be underused in this population.

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          Most cited references16

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          First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy.

          This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and >or= 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P or= PS 3 at baseline to
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            Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

            Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study.

              Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                2 February 2018
                2 January 2018
                : 9
                : 9
                : 8253-8262
                Affiliations
                1 Department of Pneumology, CHU Pontchaillou, Rennes, France
                2 Pneumo-Oncology Department, Centre Francois Baclesse, Caen, France
                3 Pneumology Department, CHU Hôpitaux de Rouen-Charles Nicolle, Rouen, France
                4 Oncology Department, Institut Paoli-Calmette, Marseille, France
                5 Pneumology Department, CH Intercommunal de Créteil, Créteil, France
                6 Oncology Department, CH Sud-Bretagne, Lorient, France
                7 Pneumology Department, Hôpital René-Dubos, Pontoise, France
                8 Pneumo-Oncology Department, Hôpital Sainte-Marguerite, Assistance Publique-Hôpitaux de Marseille, Marseille, France
                9 Pneumology Department, Hôpital Foch, Suresnes, France
                10 Cancerology Institute, CHU Brest, Brest, France
                11 Pneumology Department, CH François Quesnay, Mantes La Jolie, France
                12 UMR INSERM U1242-COSS, Rennes University, Rennes, France
                Author notes
                Correspondence to: Romain Corre, romain.corre@ 123456chu-rennes.fr
                Article
                23836
                10.18632/oncotarget.23836
                5823568
                29492192
                58aa0ebe-f7bf-47ae-b31c-7df7d6f4d70d
                Copyright: © 2018 Corre et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribut3ion, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 September 2017
                : 13 November 2017
                Categories
                Research Paper: Gerotarget (Focus on Aging)

                Oncology & Radiotherapy
                targeted therapies,tyrosine-kinase inhibitors,non-small cell lung cancer,egfr,elderly,gerotarget

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