Leszek Kraj
Klinika Hematologii, Onkologii i Chorób Wewnętrznych
Warszawski Uniwersytet MedycznySamodzielny Publiczny Centralny Szpital Kliniczny
W Warszawie
Rak trzustki – cele terapeutyczne. Sekwencja leczenia.
Rak trzustki: 5- letnie prze ycia na tle innych nowotworówżycia na tle innych nowotworów
1. SEER cancer statistics. http://seer.cancer.gov/statfacts/html/pancreas.html. Accessed August, 2013.
1. SEER cancer statistics. http://seer.cancer.gov/statfacts/html/pancreas.html.
Rak trzustki – zaawansowanie w momencie rozpoznania
Holland-Frei 9 th Edition
Podstawy diagnostyki – wytyczne ESMO
5Annals of Oncology 26 (Supplement 5): v56–v68, 2015
ChirurgiaRadioterapiaLeczenie Systemowe
Ewolucja leczenia systemowego mPC …
7
… 1997 Pancreatic Cancer:…..the era of «therapeutic nihilism»
5 FU….lepsze niż nic…..???
Gemcytabina (1997-2011)
9
Primary endpoint: Clinical BenefitSecondary endpoint: weight changeOther endpoints: ORR, survival, time to progressive disease
Burris III HA, et al. J Clin Oncol. 1997;15:2403-2413.
10
Gemcytabina (1997-2011)
Burris III HA, et al. J Clin Oncol. 1997;15:2403-2413.
Gemcytabina : badania kliniczne 2000-2010
11
12
• Phase III– Primary endpoint: OS– Secondary endpoints: PFS, tumor response, safety, quality of life
Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
Rok 2011 – PRODIGE 4 /ACCORD 11
13
Rok 2011 – PRODIGE 4 /ACCORD 11
Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
14
Rok 2013 – badanie MPACT
Von Hoff DD, et al. N Engl J Med. 2013;369:1691-1703.
Badanie MPACT - OS
15Von Hoff DD, et al. N Engl J Med. 2013 Oct 16
Badanie MPACT
16
Survival rates, %
Nab-paclitaxel + gemcitabine
(n=431)Gemcitabine
(n=430)
6 months 66 55
12 months 35 22
24 months 10 5
36 months 4 0
42 months 3 0
Goldstein D, et al. ASCO GI 2014 (abstract 178)
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-398 + 5-FU/LV (IIB)
Zalecenia ESMO
Ducreux et al. Ann Oncol 2015;26:v56-68
18
PROGRAM LEKOWY MZ – 01.2017
I linia leczenia mPC
spektrum pacjentów…
Fit pts:YoungPS 0-1
No comorbiditiesNo biliary stent (?)
Very committed
FOLFIRINOX
The unfit pt:ElderlyPS 2/3
ComorbiditiesWants treatment,
but not toxicity
GEM mono
The truly unfit pt:Old elderly
PS 3/4Jaundice not
amenable to biliary drainage
SUPPORTIVE CARE
Fit and relatively fit pts:PS 0-2
Few comorbiditiesBiliary stent
Relatively committed
nab-P/GemGiordano G. unpublished
I linia leczenia doświadczenia grupy niemieckiej (n=1174) – Top 5 najczęściej wybieranych schematów
20
Hegewisch Becker S. et al. International Journal of Cancer. July 2018 ‐Becker S. et al. International Journal of Cancer. July 2018
21
Rozsiany rak trzustki – czy jesteśmy gotowi na leczenie sekwencyjne – II , III linia leczenia ??? ….
40% pacjentów kwalifikuje się do leczenia II linii…
II/III linia leczenia doświadczenia grupy niemieckiej (n=1174)
22Hegewisch Becker S. et al. International Journal of Cancer. July 2018 ‐Becker S. et al. International Journal of Cancer. July 2018
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-398 + 5-FU/LV (IIB)
Zalecenia ESMO
Ducreux et al. Ann Oncol 2015;26:v56-68
MM-398 + 5-FU/LV – II linia leczenia (NAPOLI-1)
MM-398(120 mg/m2 Q3W)
n=151
MM-398 + 5-FU/LV
(80 mg/m2 + 2400 mg/m2 over 46 h / 400 mg/
m2 Q2W)n=117
1:1:1
Primary endpoint: OSSecondary endpoints: PFS, ORR, CA19-9 response, safety
• MPC
• Received prior gemcitabine-based therapy
• N=417
Wang-Gillam et al. Lancet 2015.
5-FU/LV(2000 mg/m2 over 24 h /
200 mg/m2 weekly Q6W) n=149
Stratification: Albumin, KPS, ethnicity
Single-agent MM-398 did not improve OS or PFS
MM-398+5-FU/LV 6.1 months (95% CI 4.8–8.9)
5-FU/LV 4.2 months (95% CI 3.3–5.3)
HR=0.67 (0.49–0.92) p=0.012
180 6 12 153 9
RANDOMIZE
117 51 8 097 20118 34 6 168 11
Time (months)01
Overall survival according to 2nd-line treatment received
Pro
babi
lity
of s
urvi
val
Overall survival (months)
48.00.0
12.0
24.0 36.0
42.06.0
18.0
30.0
0.0
0.2
0.4
0.6
0.8
1.0
A: XELOX/FOLFOXB: FOLFIRIC: FOLFIRINOXD: BSC
2nd-line schedule
Median OS: 13.8 months (95% CI 11.069-16.531)
Median OS: 12.9 months (95% CI 11.772-14.028)Median OS: 6.8 months
Median OS: 13.2 months (95% CI 10.909-15.491)
Significant difference in OS for 2nd-line treatment vs BSC; no difference in OS between 2nd-line treatments
Giordano et al. ASCO 2016
Treatment sequencing after 1st-line nab-paclitaxel + gemcitabine: Italian real-life experience
26
27
Microsatellite instability (MSI/MSH)
28
29
Hu et al. Clinical Cancer Research; March 2018
Microsatellite instability (MSI/MSH)
Kryteria amsterdamskie rozpoznania HNPCC
30
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