Rak trzustki cele terapeutyczne. Sekwencja leczenia.

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1 Rak trzustki cele terapeutyczne. Sekwencja leczenia. Leszek Kraj Klinika Hematologii, Onkologii i Chorób Wewnętrznych Warszawski Uniwersytet Medyczny Samodzielny Publiczny Centralny Szpital Kliniczny W Warszawie

2 Rak trzustki: 5- letnie przeżycia na tle innych nowotworówycia na tle innych nowotworów 1. SEER cancer statistics. Accessed August, 2013.

3 Rak trzustki zaawansowanie w momencie rozpoznania 1. SEER cancer statistics.

4 Holland-Frei 9 th Edition

5 Podstawy diagnostyki wytyczne ESMO Annals of Oncology 26 (Supplement 5): v56 v68,

6 Chirurgia Radioterapia Leczenie Systemowe

7 Ewolucja leczenia systemowego mpc 7

8 1997 Pancreatic Cancer:..the era of «therapeutic nihilism» 5 FU.lepsze niż nic..???

9 Gemcytabina ( ) Primary endpoint: Clinical Benefit Secondary endpoint: weight change Other endpoints: ORR, survival, time to progressive disease Burris III HA, et al. J Clin Oncol. 1997;15:

10 Gemcytabina ( ) Burris III HA, et al. J Clin Oncol. 1997;15:

11 Gemcytabina : badania kliniczne

12 Rok 2011 PRODIGE 4 /ACCORD 11 Phase III Primary endpoint: OS Secondary endpoints: PFS, tumor response, safety, quality of life Conroy T, et al. N Engl J Med. 2011;364:

13 Rok 2011 PRODIGE 4 /ACCORD 11 Conroy T, et al. N Engl J Med. 2011;364:

14 Rok 2013 badanie MPACT Von Hoff DD, et al. N Engl J Med. 2013;369:

15 Badanie MPACT - OS Von Hoff DD, et al. N Engl J Med Oct 16 15

16 Badanie MPACT Nab-paclitaxel + gemcitabine (n=431) Gemcitabine (n=430) 6 months months months months months 3 0 Survival rates, % Goldstein D, et al. ASCO GI 2014 (abstract 178) 16

17 Zalecenia ESMO Leczenie 1st-line treatment PS 0-1 Bilirubin <1.5 ULN FOLFIRINOX (IA) Nab-paclitaxel + gemcitabine (IA) 1st-line treatment PS 2 Bilirubin >1.5 ULN Gemcitabine (IA) 1st-line treatment Selected patients with PS 2 due to heavy tumour burden* Nab-paclitaxel + gemcitabine (IIB) 1st-line treatment PS 3/4 Symptomatic treatment 2nd-line treatment Good PS MM FU/LV (IIB) Ducreux et al. Ann Oncol 2015;26:v56-68

18 PROGRAM LEKOWY MZ

19 Fit pts: Young PS 0-1 No comorbidities No biliary stent (?) Very committed I linia leczenia mpc spektrum pacjentów FOLFIRINOX GEM mono Fit and relatively fit pts: PS 0-2 Few comorbidities Biliary stent Relatively committed Giordano G. unpublished The unfit pt: Elderly PS 2/3 Comorbidities Wants treatment, but not toxicity nab-p/gem The truly unfit pt: Old elderly PS 3/4 Jaundice not amenable to biliary drainage SUPPORTIVE CARE

20 I linia leczenia doświadczenia grupy niemieckiej (n=1174) Top 5 najczęściej wybieranych schematów Hegewisch Becker S. et al. International Journal of Cancer. July 2018 Becker S. et al. International Journal of Cancer. July

21 Rozsiany rak trzustki czy jesteśmy gotowi na leczenie sekwencyjne II, III linia leczenia???. 40% pacjentów kwalifikuje się do leczenia II linii 21

22 II/III linia leczenia doświadczenia grupy niemieckiej (n=1174) Hegewisch Becker S. et al. International Journal of Cancer. July 2018 Becker S. et al. International Journal of Cancer. July

23 Zalecenia ESMO Leczenie 1st-line treatment PS 0-1 Bilirubin <1.5 ULN FOLFIRINOX (IA) Nab-paclitaxel + gemcitabine (IA) 1st-line treatment PS 2 Bilirubin >1.5 ULN Gemcitabine (IA) 1st-line treatment Selected patients with PS 2 due to heavy tumour burden* Nab-paclitaxel + gemcitabine (IIB) 1st-line treatment PS 3/4 Symptomatic treatment 2nd-line treatment Good PS MM FU/LV (IIB) Ducreux et al. Ann Oncol 2015;26:v56-68

24 MM FU/LV II linia leczenia (NAPOLI-1) Primary endpoint: OS Secondary endpoints: PFS, ORR, CA19-9 response, safety MM FU/LV 6.1 months (95% CI ) 5-FU/LV 4.2 months (95% CI ) 1:1:1 MM-398 (120 mg/m2 Q3W) n=151 MPC Received prior gemcitabinebased therapy N=417 R A N D O MI Z E HR=0.67 ( ) p= FU/LV (2000 mg/m2 over 24 h / 200 mg/m2 weekly Q6W) n=149 MM FU/LV (80 mg/m mg/ m2 over 46 h / 400 mg/ m2 Q2W) n= Time (months) Single-agent MM-398 did not improve OS or PFS Stratification: Albumin, KPS, ethnicity Wang-Gillam et al. Lancet 2015.

25 Treatment sequencing after 1st-line nab-paclitaxel + gemcitabine: Italian real-life experience Overall survival according to 2nd-line treatment received 1.0 2nd-line schedule A: XELOX/FOLFOX B: FOLFIRI C: FOLFIRINOX D: BSC Probability of survival Median OS: 13.8 months (95% CI ) 0.2 Median OS: 6.8 months Median OS: 12.9 months (95% CI ) Median OS: 13.2 months (95% CI ) Overall 0 survival (months) Significant difference in OS for 2nd-line treatment vs BSC; no difference in OS between 2nd-line treatments Giordano et al. ASCO 2016

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28 Microsatellite instability (MSI/MSH) 28

29 Microsatellite instability (MSI/MSH) Hu et al. Clinical Cancer Research; March

30 Kryteria amsterdamskie rozpoznania HNPCC 30