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      Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database

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          Abstract

          Background

          Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification).

          Methods

          We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan–Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman’s correlation coefficient. Analyses were conducted by tumor subtype.

          Results

          20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8–6.2) for HR-/HER2 − subtype to 13.3 months (36% CI 12.7–14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR − /HER2 − mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies.

          Conclusions

          Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12916-023-02754-5.

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          Most cited references38

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

            This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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              A note on quantifying follow-up in studies of failure time.

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                Author and article information

                Contributors
                C.bellera@bordeaux.unicancer.fr
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                8 March 2023
                8 March 2023
                2023
                : 21
                : 87
                Affiliations
                [1 ]GRID grid.412041.2, ISNI 0000 0001 2106 639X, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Epicene Team, ; UMR 1219, 33000 Bordeaux, France
                [2 ]GRID grid.418189.d, ISNI 0000 0001 2175 1768, Unicancer, ; 101 Rue de Tolbiac, 75654 Paris, France
                [3 ]GRID grid.418189.d, ISNI 0000 0001 2175 1768, Biometrics Unit, Institut du Cancer de Montpellier, ; 208 Rue Des Apothicaires, 34298 Montpellier, France
                [4 ]GRID grid.121334.6, ISNI 0000 0001 2097 0141, University of Montpellier, ; 163 Rue Auguste Broussonnet, 34090 Montpellier, France
                [5 ]GRID grid.418189.d, ISNI 0000 0001 2175 1768, Department of Medical Oncology, , Institut du Cancer de Montpellier, ; 208 Rue Des Apothicaires, 34298 Montpellier, France
                [6 ]GRID grid.488845.d, ISNI 0000 0004 0624 6108, Institut de Recherche en Cancérologie de Montpellier (IRCM) INSERM U1194, ; 208 Rue Des Apothicaires, 34298 Montpellier, France
                [7 ]GRID grid.418596.7, ISNI 0000 0004 0639 6384, Department of Biostatistics, , Institut Curie, ; 35 Rue Dailly, 92210 Saint-Cloud, France
                [8 ]GRID grid.418191.4, ISNI 0000 0000 9437 3027, Department of Medical Information, , Institut de Cancérologie de L’Ouest Nantes & Angers, ; 15 Rue André Boquel, 49055 Angers, France
                [9 ]GRID grid.418113.e, ISNI 0000 0004 1795 1689, Department of Medical Oncology, , Centre Jean Perrin, ; 58 Rue Montalembert, 63011 Clermont Ferrand, France
                [10 ]GRID grid.489940.8, Department of Biometry, , Institut de Cancérologie de Bourgogne, ; 21079 Dijon, France
                [11 ]GRID grid.452351.4, ISNI 0000 0001 0131 6312, Centre Oscar Lambret, ; 3 Rue Frédéric Combemale, 59000 Lille, France
                [12 ]GRID grid.418116.b, ISNI 0000 0001 0200 3174, Department of Biometry, , Centre Léon Bérard, 28 Prom. Léa Et Napoléon Bullukian, ; Lyon, 69008 France
                [13 ]GRID grid.418443.e, ISNI 0000 0004 0598 4440, Institut Paoli-Calmettes, ; SESSTIM UMR912, 232, Boulevard Sainte-Marguerite, 13009 Marseille, France
                [14 ]Aix-Marseille Université, Inserm, IRD, SESSTIM Sciences Économiques Et Sociales de La Santé Et Traitement de L’information Médicale, 13009 Marseille, France
                [15 ]GRID grid.418189.d, ISNI 0000 0001 2175 1768, Department of Medical Oncology, , Centre François Baclesse, ; 3 Avenue du Général Harris, 14000 Caen, France
                [16 ]GRID grid.452436.2, ISNI 0000 0000 8775 4825, Medical Oncology Department, , Institut de Cancérologie de Lorraine, ; 6 Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France
                [17 ]GRID grid.418191.4, ISNI 0000 0000 9437 3027, Department of Pharmacy, , Institut de Cancérologie de L’Ouest Nantes, ; Bd Professeur Jacques Monod, 44800 Saint-Herblain, France
                [18 ]GRID grid.417812.9, ISNI 0000 0004 0639 1794, Department of Biometry, , Centre Antoine Lacassagne, ; 33 Avenue de Valambrose, 06189 Nice, France
                [19 ]GRID grid.418596.7, ISNI 0000 0004 0639 6384, Department of Medical Information, , Institut Curie, ; 26 Rue d’Ulm, 75005 Paris, France
                [20 ]Department of Pharmacy, Institut de Cancérologie Jean-Godinot, 1 Rue du Général Koenig, 51100 Reims, France
                [21 ]GRID grid.417988.b, ISNI 0000 0000 9503 7068, Department of Medical Information, , Centre Eugène Marquis, ; Avenue de La Bataille Flandres-Dunkerque, 35000 Rennes, France
                [22 ]GRID grid.512000.6, Department of Medical Oncology, , Institut de Cancérologie Strasbourg Europe (ICANS), ; 17 Rue Albert Calmette, 67200 Strasbourg, France
                [23 ]GRID grid.417829.1, ISNI 0000 0000 9680 0846, Department of Biometry, , Institut Claudius Regaud – IUCT Oncopole, ; 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France
                [24 ]GRID grid.418189.d, ISNI 0000 0001 2175 1768, Department of Medical Information, , Centre Henri Becquerel, ; Rue d’Amiens, 76000 Rouen, France
                [25 ]GRID grid.476460.7, ISNI 0000 0004 0639 0505, Inserm CIC1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, ; 33000 Bordeaux, France
                [26 ]GRID grid.14925.3b, ISNI 0000 0001 2284 9388, Department of Cancer Medicine, , Gustave Roussy Cancer Campus, ; 114 Rue Edouard Vaillant, 94800 Villejuif, France
                Article
                2754
                10.1186/s12916-023-02754-5
                9993797
                36882736
                ddfde508-95f2-4577-a17c-823623e114ba
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 4 July 2022
                : 25 January 2023
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2023

                Medicine
                real-word data,breast cancer,overall survival,progression-free survival,association,surrogacy
                Medicine
                real-word data, breast cancer, overall survival, progression-free survival, association, surrogacy

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