ESMO SUMMIT RUSSIA 2019
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ESMO SUMMIT RUSSIA 2019 Practice changing trials in pancreatic and liver cancer Pokataev Ilya N/N/ Blokhin Russian Cancer Research Center
Transcript of ESMO SUMMIT RUSSIA 2019
ESMO SUMMIT RUSSIA 2019
Practice changing trials in pancreatic and liver cancer
Pokataev Ilya
N/N/ Blokhin Russian Cancer Research Center
CONFLICT OF INTEREST DISCLOSURE
Sanofi, AstraZeneca, Merck, Биокад – honoraria for educational reports, advisory boards and travel grants
RESECTABILITY CRITERIA FOR NONMETASTATIC PANCREATIC CANCER
NCCN guidelines V. 1.2019 Pancreatic adenocarcinoma
RESECTABILITY CRITERIA FOR NONMETASTATIC PANCREATIC CANCER
NCCN guidelines V. 1.2019 Pancreatic adenocarcinoma
Neoadjuvant chemotherapy ±RT
PREOPANC TRIAL: NEOADJUVANT CRT IN RESECTABLE AND BORDERLINE RESECTABLE PANCREATIC CANCERReduces resection rate but increases overall survival
(Borderline) resectable PC RGem + RTGemcitabine
Gemcitabine х 6 cyclesSurgery
Gem Surgery Gemcitabine х 4 cyclesN=244 patients
Neoadjuvant therapy
Versteijne E. et al. ASCO 2018
Versteijne E. et al. ASCO 2018
Overall survival (all patients - ITT) R0/R1 resections
Р=0.074
(Borderline) resectable PC RGem + RTGemcitabine
Gemcitabine х 6 cyclesSurgery
Gem Surgery Gemcitabine х 4 cyclesN=244 patients
Neoadjuvant therapy
PREOPANC TRIAL: NEOADJUVANT CRT IN RESECTABLE AND BORDERLINE RESECTABLE PANCREATIC CANCERReduces resection rate but increases overall survival
PREP-02/JSAP-05: PREOPERATIVE CHEMOTHERAPY IN RESECTABLE PCIncreases resection rate
Resectable PC R
Gem+ S1
Adjuvant S1Surgery
Surgery
Michiaki Unno et al. ASCO GI 2019
n=180
Adjuvant S1 n=180
Stratification:•Са19-9 level•Center
PREP-02/JSAP-05: PREOPERATIVE CHEMOTHERAPY IN RESECTABLE PCIncreases overall survival
26,7 mo 36,7 mo
Overall survival
Р=0,015
Subgroup analysis
Michiaki Unno et al. ASCO GI 2019
Lancet Gastroenterol Hepatol 2018 in Print
Confirmed PCI-II stages
No SMV, SMA, PV, CA, CHA
KPS>60%
Surgery
PEXG х 3 cyclesSurgery
Gemcitabine х 6 cycles
N=88
Surgery
PEXG х 6 cycles(cisplatin 30 mg/m2, epirubicin 30 mg/m2, gemcitabine800 mg/m2 1, 15 days q4 weeks and capecitabine 1250 mg/m2 1-28 days)
A
B
C PEXG х 3 cycles
PACT15 results (median follow-up 55 months)Overall survival
20,4 26,4 38,2
Lancet Gastroenterol Hepatol 2018 in Print
SWOG S1505 TRIAL: FIRST DATA
Sohal D. et al. ASCO 2019
Findings at central radiology review Adverse events
SWOG S1505 TRIAL: FIRST DATAReasons for not reaching surgery
Sohal D. et al. ASCO 2019
TALE HOME MESSAGE
Preoperative therapy of initially resectable pancreatic cancer increases survival The risk associated with the following:
- time for morphological confirmation, - time for bile duct decompression,- adverse events of preoperative therapy, - progression on the preoperative therapy,
is acceptable.We are awaiting the results of other studies on pre- / perioperative treatment with combination chemotherapy (eg, FOLFIRINOX)
- What is the role of radiation therapy in preoperative treatment?
Adjuvant chemotherapy is the standard of care in pancreatic cancer
ESPAC-1: фторурацил CONCO001: гемцитабин
ESPAC4: GEMCAP
Inclusion criteria : 18 -79 years old ECOG 0 or1 No prior radio- or chemotherapy No postoperative complications Total bilirubin ≤ 1.5 х ULN, creatinine clearance ≥ 50 ml/min
35 54,4 12,8 21,6
Conroy T. et al. N Engl J Med 2018;379:2395-406.
PRODIGE24: THE TOXICITY OF THE ADJUVANT THERAPY FOLFIRINOX AND GEMCITABINE
Conroy T. et al. N Engl J Med 2018;379:2395-406.
•ECOG 0-1•T.bilirubin<1,5 x ULN, creatinine clearance > 50•Central venous access •The possibility of 46-hour 5FU infusion•The possibility of hospitalization in a specialized clinic in case of life-threatening complications
ECOG 2Elderly age
Concomitant pathology
mFOLFIRINOX
Gem or 5FU monotherapy
The adjuvant therapy selection algorithm is based on the patient’s condition
ECOG 3BSC
No chemo
ECOG 0-1,
Selected patients with ECOG 2 GEMCAP
RUSSCO Clinical guidelines 2018
APACT TRIAL: GEMCITABINE+ NAB-PACLITAXELVSGEMCUTABINE IN ADJUVANT CHEMOTHERAPY OF PANCREATIC CANCER
Stratification:•R0/R1•N0/N1•Region: North America, Europe, Australia vs Asia
Tempero M. et al. ASCO 2019
APACT TRIAL: GEMCITABINE+ NAB-PACLITAXELVSGEMCUTABINE IN ADJUVANT CHEMOTHERAPY OF PANCREATIC CANCER
Tempero M. et al. ASCO 2019
Primary end-pointDisease-free survival (independent radiology
review)Disease-free survival (investigator assessed )
APACT TRIAL: GEMCITABINE+ NAB-PACLITAXELVSGEMCUTABINE IN ADJUVANT CHEMOTHERAPY OF PANCREATIC CANCER
Tempero M. et al. ASCO 2019
Secondary end-pointOverall survival
CLINICAL GUIDELINES FOR METASTATIC PANCREATIC CANCER
RUSSCO 2018: in case of germline or somatic deleterious BRCA mutation FOLFIRINOX or platinum + gemcitabine is recommended options
RUSSCO clinical guidelines 2018Ducreux M. et al. Annals of Oncology 26 (Supplement 5): v56–v68, 2015
ESMO 2015
POLO TRIAL: OLAPARIB VS PLACEBO IN IN MAINTENANCE TREATMENT OF BRCA-ASSOCIATED PANCREATIC CANCER
Kindler H. et al. ASCO 2019
38% patients were not randomized due to progression on chemotherapy
POLO TRIAL
Kindler H. et al. ASCO 2019
POLO TRIALResults
Golan T. et al. n engl j med 2019 (in print)
Progression-free survival Overall survival (maturity 46%)
POLO TRIALThe rate of objective responses and their duration
Kindler H. et al. ASCO 2019
There is no benefit in overall survival yet Comparison with placebo (instead of maintenance chemotherapy until progression)
could affect the difference in progression-free survival Not all patients respond to treatment with olaparib Abstract 4132 (ASCO19): MSKCC data
33% patients with pancreatic cancer have monollagenic BRCA mutations in the tumor (germline and somatic)
TAKE HOME MESSAGES FROMPOLO TRIAL
CHOLANGIOCELLULARCANCER
CURRENT ESMO GUIDELINES FOR BILIARY TRACT CANCER
Valle J.W. et al. Annals of Oncology 27 (Supplement 5): v28–v37, 2016
BILCAP: capecitabine is a
standard of adjuvant chemo
•АВС-002: CisPt + Gem– the standard of I line CT (replacement for oxaliplatin in renal impairment)•No standard 2nd line chemotherapy
Slide 3
Presented By Angela Lamarca at 2019 ASCO Annual Meeting
Slide 11
Presented By Angela Lamarca at 2019 ASCO Annual Meeting
Slide 12
Presented By Angela Lamarca at 2019 ASCO Annual Meeting
HEPATOCELLULAR CANCER
Hepatocellular Carcinoma
Presented By Bruno Sangro at 2019 Gastrointestinal Cancer Symposium
RCT Design (from April 2009)
Presented By Namiki Izumi at 2019 ASCO Annual Meeting
Kaplan-Meier estimate of RFS
Presented By Namiki Izumi at 2019 ASCO Annual Meeting
Forest plots of RFS in patient subgroups
Presented By Namiki Izumi at 2019 ASCO Annual Meeting
Adverse Events
Presented By Namiki Izumi at 2019 ASCO Annual Meeting
Conclusion
Presented By Namiki Izumi at 2019 ASCO Annual Meeting
HEPATOCELLULAR CANCER (3 YEARS AGO)
Chemoresistance tumor: - - the response rate on any chemotherapy is less than 10%, there is no data on
the increase in life expectancy -Sorafenib - the standard of first-line treatment of metastatic HCC -Adding chemotherapy to sorafenib does not improve the outcome:
- - sorafenib + doxorubicin vs sorafenib: median OS 8.9 and 10.5 monthsThere was no second line chemotherapy standard
PHASE III STUDY: LENVATINIB VSSORAFENIBNon-inferiority design
Kudo M. et al. Lancet 2018; 391: 1163–73
Progression-free survival Overall survival
THE RESULTS OF PHASE II - III STUDIES IN 2ND LINE SETTING
Regorafenib Cabozantinib Ramucirunab
Bruix et al. Lancet 2017; Abou-Alfa NEJM 2018; Zhu et al. Lanet Oncol 2019; Finn at al. ASCO 2019
Pembrolizumab
Treatment Options for HCC in 2019
Sorafenib1 линия
2 линия
Approved New options with the data for 2018-2019
Lenvatinib
Regorafenib
Pembolizumab
Ramucirumab Cabozantinib
Durvalumab+/- tremelimumab?
Atezolizumab + bevacizumab?
Nivolumab
Nivolumab + ipilimumab?
Pembrolizumab + lenvatinib?
