Patients with Metastatic Melanoma Receiving Anticancer Drugs: Changes in Overall Survival, 2010–2017

Immune checkpoint inhibitors and targeted therapies have profoundly altered the management of several cancers over past decade. Metastatic melanoma has been at forefront these changes. We provide here a nationwide overview an assessment changes in survival France. included 10,936 patients receiving systemic treatment for metastatic cutaneous between 2010 2017 using French National Health Insurance database (Système des Données de Santé). Over study period, there was doubling number new treatment. Cytotoxic chemotherapy progressively replaced by therapy immune inhibitors. Patients having initiated first-line since June 2015 gained 46% overall compared with those initiating before 2012. Overall 24 months rose from 21% to 44%. real-world evidence improvement decade among melanoma. Although characteristics treated can vary across periods, this type exhaustive data provides broader populations than clinical trials. recent oncology. For almost 40 years, cytotoxic used had associated median less 12 (Balch et al., 2009Balch C.M. Gershenwald J.E. Soong S.J. Thompson J.F. Atkins M.B. Byrd D.R. al.Final version 2009 AJCC staging classification.J Clin Oncol. 2009; 27: 6199-6206Crossref PubMed Scopus (3529) Google Scholar). The emergence anticancer drugs last 10 years changed strategies, because each demonstrated gains reference randomized controlled trials (RCTs) (Eggermont Robert, 2011Eggermont A.M.M. Robert C. New melanoma: it’s whole world.Eur J Cancer. 2011; 47: 2150-2157Abstract Full Text PDF (155) Scholar; Ugurel 2017Ugurel S. Röhmel J. Ascierto P.A. Flaherty K.T. Grob J.J. Hauschild A. al.Survival advanced impact novel therapies-update 2017.Eur 2017; 83: 247-257Abstract (176) Novel therapeutic approaches (ICIs) therapies. A first wave started 2011 anti–CTLA-4 drug ipilimumab BRAF Since 2015, agents targeting PD-1 combined MAPK/extracellular signal–regulated kinase (MEK) become standards. extent which translated into real world remains be further investigated. insurance identify all who received Our objectives were describe use analyze on (OS) period. Every patient beginning France included. numbers per trimester January December are presented Figure 1. more doubled 910 1,890 2017. Drastic modalities observed whenever became available (Figure 1), leading very distinct profiles our four cohorts. only option cohort 1, entirely subsequent Vemurafenib, inhibitor, starting date 2. Cohort 3 access as additional option. hallmarks 4 availability anti–PD-1 antibodies combination MEK Therefore, cohorts reflected time periods categories options 1c). Age, sex, comorbidities fairly stable (Table 1).Table 1Demographic Characteristics MelanomaCharacteristicCohort 1January 2010–December n = 1,808Cohort 2January 2012–October 2013 2,069Cohort 3November 2013–May 2,334Cohort 4June 2015–December 4,725Sex, (%) Men1,015 (56)1,187 (57)1,369 (59)2,733 (58) Women793 (44)882 (43)965 (41)1,992 (42)Age, y Median (IQR)66 (54–77)65 (53–76)67 (54–76)68 (54–78) Mean (SD)65 (15)64 (15)65 (15)Comorbidities,1Recorded initiation treatment, algorithm developed Bannay al. (2016) Charlson comorbidity index Electronic Care database. Myocardial infarction9 (0.5)17 (0.8)22 (0.9)49 (1.0) Congestive heart failure43 (2)73 (4)66 (3)161 (3) Peripheral vascular disease56 (3)71 (3)66 (3)169 (4) Cerebrovascular disease75 (4)92 (5)100 (4)237 (5) Dementia11 (1)17 (1)15 (1)43 (1) Chronic pulmonary disease137 (8)175 (9)189 (8)432 (9) Connective tissue disease24 (1.3)25 (1.2)20 (0.9)62 (1.3) Ulcer disease14 (0.8)11 (0.5)12 (0.5)21 (0.4) Mild liver disease35 (2)34 (2)31 (1)71 (2) Diabetes148 (8)222 (11)259 (11)556 (12) Diabetes end-organ damage32 (2)36 (2)37 (2)85 Moderate or severe renal disease50 (3)61 (3)171 Hemiplegia58 (3)86 (4)193 disease6 (0.3)3 (0.1)5 (0.2)19 HIV infection2 (0.1)6 (0.3)6 (0.3)7 (0.2)Charlson index2Age-adjusted (Bannay 2016; 1994).,3Minimum score 8 cancer (two points) stage (six points). (IQR)8 (8–9)8 (8–9) (SD)8 (1)9 (1)Metastatic sites,4Identified hospitalization discharge codes after Lymph node994 (55)1,156 (56)1,275 (55)2,452 (52) Lung881 (49)957 (46)982 (42)1,761 (37) Liver549 (30)628 (30)553 (24)1,063 (23) Brain564 (31)674 (33)622 (27)1,081 Bone380 (21)427 (21)409 (18)837 (18)Number sites4Identified (SD)2.9 (1.6)2.8 (1.6)2.6 (1.5)2.5 (1.5)Surgical resection,5Within Lymphadenectomy412 (23)594 (29)713 (31)1,536 (33) Subcutaneous metastases342 (19)403 (20)169 (20)962 (20) Distant metastases6Mainly including brain, digestive, liver, sites.224 (12)224 (11)254 (11)514 (11)Radiotherapy,5Within (%)132 (7)295 (14)271 (12)507 (11)Abbreviation: IQR, interquartile range.Patients broken down successive cohorts, according period they began treatment.1 Recorded 2016Bannay Chaignot Blotière P.O. Basson M. Weill Ricordeau P. al.The best electronic health care predict mortality.Med Care. 54: 188-194Crossref (169) Scholar database.2 Age-adjusted 1994Charlson Szatrowski T.P. Peterson Gold Validation index.J Epidemiol. 1994; 1245-1251Abstract (4138) Scholar).3 Minimum points).4 Identified treatment.5 Within treatment.6 Mainly sites. Open table tab Abbreviation: range. cohort, visual representation vital status lines 6 is These descriptive show how variety impacts trajectories, not treatments but also lines. OS 2, 3, Crude hazard ratios 95% confidence intervals (CIs) 0.93 (0.87–1.00), 0.69 (0.64–0.74), 0.54 (0.50–0.57), respectively. After adjustment age, (congestive failure, cerebrovascular disease, chronic disease), location sites (lymph node, lung, bone), surgical resection distant metastases, radiotherapy (95% CI) 0.92 (0.85–0.98), 0.72 (0.67–0.77), 0.56 (0.52–0.60). Median, 1-year, 2-year results provided Table curves 3. estimated effects characteristics, sites, prior resection, shown Supplementary S1.Table 2Comparative Four Cohorts Melanoma FranceOSCohort 4,725Median OS, mo CI)8.5 (7.9–9.0)8.6 (7.9–9.1)12.5 (11.4–13.5)18.0 (16.8–19.6)12-mo % CI)38.7 (36.4–40.9)39.8 (37.7–41.9)50.5 (48.5–52.5)59.4 (57.8–60.9)24-mo CI)21.2 (19.4–23.1)23.8 (21.9–25.6)36.0 (34.1–38.0)44.4 (42.4–46.3)Abbreviations: CI, interval; survival. Abbreviations: two most widely prescribed within S2). obtained (n 2,605; 22.5 months, CI 19.2–25.7; 24-month 48.4% 45.7–51.1%). 832) 16.3 13.6–18.8) 42.2% 38.8–45.5%). Targeted (which shifted inhibitor monotherapy inhibitors) increasingly better (median 10.6 [9.5–11.8] 2 15.9 [14.9–17.7] 4; 24.4% [21.2–27.5%] 39.6% [36.4–42.8%]). From large level, we report 2010–2017 routinely collected potential important information public perspective (Booth 2019Booth Karim Mackillop W.J. 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