Management Of Patients With Metastatic Colorectal Cancer in Lebanese Hospitals and Associated Direct Cost: A Multicenter Cohort Study

Transcription

1 Management Of Patients With Metastatic Colorectal Cancer in Lebanese Hospitals and Associated Direct Cost: A Multicenter Cohort Study Henaine AM; Chahine G; Massoud M; Salameh P; Awada S; Lahoud N; El Kak A ; Salem M; Ballout S; Hartmann D; Aulagner G; Armoiry X

2 Introduction *Cytotoxic agents clinically and costeffective treatments Recently, monoclonal antibodies *2 d in females and the 4 th in males [average of 630 individuals annually in Lebanon in 2012] No vital statistics in terms of morbidity or mortality but its incidence rate, per , by colon and rectum sites, in 2015, was 17.6 and 7.5 respectively Mortality rates Advances in technology and colonoscopy examination, screening, diagnosis and improved surgery + adjuvant chemotherapy and palliative care survival benefits + symptom control and palliation *Henaine AM, Chahine G, Salameh P, Elias E, Massoud M, Hartmann D, Aulagner G, Armoiry X. Management of metastatic colorectal cancer: current treatment and new therapies. Journal Médical Libanais, 2015; 63(4): Henaine Ana Maria declare to meeting attendees that there are no financial relationships with any for-profit companies that are 06/12/2017 directly or indirectly related to the subject of my presentation 2

3 Metastatic Colorectal Cancer : Introduction mcrc Liver, lungs, peritoneum.. Colon TNM Treatment Rectum Mutations (KRAS/NRAS/BRAF) Cytotoxic Therapy (5FU/LV, Oxaliplatin, Irinotecan) Targeted Therapy (Bevacizumab/Cetuximab) 06/12/2017 Henaine Ana Maria declare to meeting attendees that there are no financial relationships with any for-profit companies that are directly or indirectly related to the subject of my presentation 3

4 Objectives The way those novel therapies are used and positioned in daily routine practice + their related effectiveness and costs not well documented in Lebanon Evaluate the management of patients with mcrc in 2 Specialized Oncologic Lebanese Hospitals Compare effectiveness of cytotoxic agents and targeted therapy along with their estimated direct cost 06/12/2017 4

5 Pattern Of Care of Lebanese Patients Free-Of-Charge OUT No coverage Hospitalization 85% Spécial for laboratory tests, imaging, physician consultations MH Lebanese Army All members of the Intern Force and Lebanese Army with their families are covered :100% et 75% respectively All People, taxi-drivers, students Paye 90% medical ressource consumption, 85% in general chemotherapy NSSF and Insurances Cooperative All members and families 90% hospitalization costs, 75% out costs. Cieling level in paiement 06/12/2017 5

6 Patients and Methods Prospective cohort study 2 Lebanese Hospitals ( ) Medical therapy, OS, total costs Selection Criteria Histologically confirmed adenocarcinoma of the colo-rectum, With one or more metastases and No previous chemotherapy for metastatic disease. Non-selection Criteria Death from non-oncologic reason or other co-morbidities Known allergy to monoclonal antibodies Cytotoxic or conventional Targeted or biological 06/12/2017 6

7 Costs For Every Single Treatment (Tarifs 2013) Drug Administration Price/Injection Cost/Dose Cost/Cycle (2 weeks) Bevacizumab 100 mg= 718$ 5 mg/kg/d/2 weeks 2443$ 7329 $ 400 mg = 2443$ Cetuximab LD: 400 mg/m 2 5mg/ml (20 ml) = 351 $ MD: 250 mg/ m 2 5mg/ml (100ml) = 1467$ 2520$ 3573 $ XELOX (Cycle of 21d) Oxaliplatin : 1481 $ Capecitabine : 428 $ FOLFOX-6 (Cycle of 14d) Oxaliplatin:1139 $ Leucovorin : 76 $ 5-FU (Bolus) : 2,5 $ 5-FU (Perfusion) : 14.9$ FOLFOX-4 (Cycle of 14d) Oxaliplatin: 969 $ Leucovorin: 76 $ 5-FU (Bolus) : 2,5$ 5-FU (Perfusion): 3.71 $ FOLFIRI (Cycle of 14d) Irinotécan : 518 $ Leucovorin : 76 $ 5-FU (Bolus) : 2,5 $ 5-FU (Perfusion) : 3,71$ Total = 1909 $ Total = 1233 $ Total = 1051 $ Total = 600 $ 06/12/2017 7

8 Effectiveness/End points Effectiveness OS Mean time from diagnosis to death (or date of last followup at time of data collection) Primary End points Overall Survival (OS), Progression-Free-Survival (PFS), RECIST (PD, TRR, RR, DP) and Costs Costs analysis: Lebanese Sickness Fund perspective using tariffs from 2013 in US dollars ($) Direct costs, only for chemotherapy medications (and biotherapy), costs/treatment-cycle and total costs /patient. We did not include the cost of administration, supportive medications, physician consultations or treatment of complications Indirect costs (transportation costs, surgery, imaging tests) have not been taken into account due to difficulties in accessing administrative medical records 06/12/2017 8

9 Characteristics Total (%) Cytotoxic group (N/%) Cytotoxic + Targeted General Baseline Characteristics Of The 179 Patients group (N/%) Arms of treatment (26.8%) 131 (73.2%) - Age at diagnosis, years Range Mean¹ 26-89y 60.5 y ± y 63y ± y 59.5y ± 12.9 p-value Males / Females 103 (57.5%)/76 (42.5%) 28 (58%) /20 (42%) 75 (57%) / 56 (43%) Colorectal Rectal Liver only Liver and others Non liver 1 2 Wild KRAS Mutated KRAS CEA only Ca19.9 only Both increased Neither increased 152 (84.9%) 27 (15.1%) 50 (28%) 76 (43%) 53 (29%) 92 (52%) 86 (48%) 93 (52%) 27 (15.1%) 55 (31%) 11 (6%) 50 (28%) 63 (35%) 38 (79%) 10 (21%) 21 (44%) 8 (17%) 19 (39%) 40 (85%) 7 (15%) 11 (23%) 2 (4%) 10 (21%) 3 (6%) 7 (15%) 28 (58%) (87%) (13%) 29 (22%) 68 (52%) (26%) 52 (40%) (60%) 82 (63%) 25 (19%) (34%) 8 (6%) 43 (33%) 35 (27%) 06/12/

10 Cytotoxic and Targeted Chemotherapy Applied In The 3 Lines Of Treatment (After Relapse) Treatment 1 rst line 2 nd line 3 rd line p-value Conventional (chemotherapy) Targeted 154 (86%) 25 (14%) 72 (42%) 99 (58%) 11 (11%) 88 (89%) <0.001 Treatment strategies Targeted (associated to chemotherapy): Cetuximab Bevacizumab Conventional chemotherapy: 5FULV XELOX FOLFOX FOLFIRI FOLFOXIRI XELIRI 1,1% 13,0% 36,3% 25,7% 38,6% 1,1% % 47,3% 0,6% 37,4% 43,3% 12,9% 16,4% 4,7% 15,6% 84,4% 8,3% 24,0% 47,0% 5,2% 1,1% 34,4% NS 06/12/

11 Outcomes Tumor Assessment Responses And Effectiveness (all protocols confused) Cytotoxic (N=153) 1 rst line Targeted + Cytotoxic (N=25) *p Cytotoxic (N=71) 2 nd line Targeted+ Cytotoxic (N=99) *p Cytotoxic (N=11) 3 rd line Targeted+ Cytotoxic (N=88) TRR CR 6(4%) 1(4%) 18(25%) 7(7%) 1(9%) 6(7%) PR 20(13%) 3(12%) 12(17%) 4(4%) 1(9%) 6(7%) Stability 67(44%) 10(40%) 21(29%) 42(43%) 0(0%) 17(19%) Progression 60(40%) 11(44%) (29%) 46(46%) (82%) 59(67%) 0.5 DCR (%) RR (%) PD (%) PFS (months) /12/ *p

12 ahr=0.76, 95% CI= ; p=0.379 ahr=1.14, 95% CI= ; p =0.572 Cox Survival curves showing the differences on survival between the 2 groups and 3 lines of therapy respectively (sensitivity analysis NS) ahr =0.84, 95% CI= ; p =0.576 ahr=1.94, 95% CI= ; p =0.079 The median of survival in the whole population was 20.8 months (CI 95%= 10.7 month-30.9 month) and 49.7% still alive 06/12/

13 Average Overall Total Cost ($) /Arms Of Treatment 1 rst line 2 nd line 3 rd line Total p-value Cytotoxic group ($) Mean ± St dev 7961 ± ± ± ± Minimum <0.05 Maximum Median Targeted +Cytotoxic group ($) Mean ± St dev ± ± ± ± Minimum <0.05 Maximum Median Global Cost ($) Mean ± St dev ± ± ± ± Minimum <0.05 Maximum Median 06/12/

14 Box-Plot Diagram Of The Total Global Costs Total cost of treatment Conventional treatment Addition of targeted therapy to conventional treatment 06/12/

15