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)

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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

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Rok 2011 – PRODIGE 4 /ACCORD 11

Conroy T, et al. N Engl J Med. 2011;364:1817-1825.

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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

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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

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Hegewisch Becker S. et al. International Journal of Cancer. July 2018 ‐Becker S. et al. International Journal of Cancer. July 2018 

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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)

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29

Hu et al. Clinical Cancer Research; March 2018

Microsatellite instability (MSI/MSH)

Kryteria amsterdamskie rozpoznania HNPCC

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