- Email: [email protected]
New evidences of chemotherapy in biliary tract cancer
Annals of Oncology 30 (Supplement 6): vi30, 2019 doi:10.1093/annonc/mdz348
SY4 1
New evidences of chemotherapy in biliary tract cancer
Do-Youn Oh Medical Oncology, Seoul National University Hospital, Korea There are huge unmet medical needs in biliary tract cancer. Biliary tract cancer is nonrare cancer in Asia especially in Korea. As a 1st-line chemotherapy, gemcitabine/cisplatin is current standard of care, and in 2nd-line setting, FOLFOX improved overall survival compared with best supportive care. Biliary tract cancer is a heterogenous group not only in primary origin but also molecular characteristics. Somatic alterations in the KRAS, TP53, CDKN2A, SMAD4, BAP1, ARID1A, PBRM1 and IDH1/2 have been reported. In recent study, 38.9% of biliary tract cancer cases harbor potentially targetable genetic alteration including FGFR1, FGFR2, FGFR3, PIK3CA, ALK, EGFR, ERBB2, BRAF, AKTS, IDH1, IDH2, CCND1, CCND3, MDM2, BRCA1 and BRCA. Targeting those molecular alterations are now being tried in clinical trials. Among them, targeting FGFR alteration especially FGFR2 fusion is far advanced in its clinical development, which is being followed by targeting mutant IDH1. This is era of immunotherapy in cancers. Mutant IDH inhibits HNF-4a to block hepatocyte differentiation and promote biliary cancer. A vaccine targeting mutant IDH1 induces antitumor immunity. Cholangiocarcinoma which harbor neoantigen by oncogene mutation could be candidate for adoptive transfer for TIL containing mutationspecific T cell. Anti-PD1 or PDL1 antibody has shown the promising antitumor efficacy in biliary tract cancer. PD1/PDL1 inhibitor with CTLA4 inhibitor or chemotherapy in combination with PD1/PDL1 inhibitor are under investigation. New drug development strategy including targeted agents and immuno-oncology might be enormously tested in biliary tract cancer. The integration of precision medicine might be one of key factors for the success of new drug development including targeted agents and immuno-oncology agents.
SY4 2
Precision Oncology for Pancreatic Cancer across the United States: R experience the Know Your Tumor V
Lynn M. Matrisian1, Edik M Blais2, Emily Lyons1, Cassadie Moravek1, Patricia Dearbeloa2, Subha Madhavan2,3, Jonathan R Brody4, Emanuel Petricoin2,5, Michael J Pishvaian2,6 1 Pancreatic Cancer Action Network, United States, 2Perthera, Inc, 3Georgetown University, 4Thomas Jefferson University, 5George Mason University, 6M.D.Anderson Cancer Center The Know Your Tumor initiative identifies pancreatic cancer patients across the USA eligible for molecular testing through the Pancreatic Cancer Action Network call center. Perthera, Inc obtains patient consent, coordinates molecular testing, convenes a virtual molecular tumor board, prepares a report with a ranked list of therapy options, and collects outcomes. More than 1800 patients have been enrolled from 49 states and more than 1100 reports have been delivered. DNA testing was primarily with the Foundation
Medicine panel of 324 genes and includes microsatellite instability (MSI). Therapy options include clinical trials, off-label treatments, or standard-of-care chemotherapy. Approximately one quarter (26%) of patients were identified with highly actionable (HA) alterations defined as molecular alterations for which a targeted therapy is indicated based on data in any cancer type. HA alterations include mutations in BRCA1/2, ATM, PALB2 and other DNA damage-repair genes indicating treatment with a PARP inhibitor, MSI-High with a PD-1 inhibitor, and alterations in RET, NTRK, BRAF, ALK, ROS, CDK4/6, FGF, and ROS with specific targeted agents. Patients treated in the advanced setting with HA alterations who received a molecularly-matched therapy (n ¼ 46) had a significant 1-year improvement in overall survival compared to those with HA alterations who had no molecularly-matched therapies (HR ¼ 0.42, p¼.0004, n ¼ 143) or those with no HA alterations (HR ¼ 0.34, p¼.000002, n ¼ 488). Progression-free survival for those receiving a molecular matched therapy as 2nd line or greater therapy (10.93 mos, n ¼ 38) was 2.4-fold greater than those with HA alterations and their best unmatched therapy (4.53 mos, p ¼ 0.01, n ¼ 84) and 2-fold greater than those without HA alterations (5.37 mos, p ¼ 0.01, n ¼ 288). These results provide evidence in a real-world setting that support the recent change in NCCN guidelines recommending tumor profiling for patients with advanced pancreatic cancer.
SY4 5
Second line chemotherapy for advanced pancreatic cancer patients in Japan
Tatsuya Ioka Dept of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute I would introduce the second-line chemotherapy for metastatic pancreatic cancer (mPC) in Japan recently. We have two standards of care for mPC patients with good performance status as the first-line chemotherapy. One is FOLFIRINOX or modified FOLFIRINOX (mFFX), and another is Gemcitabine (Gem) plus nab-paclitaxel (GnP). We usually choose GnP or Gem monotherapy for FOLFIRINOX or mFFX refractory patients, and we usually choose mFFX or S-1 monotherapy for GnP refractory patients as the second-line chemotherapy, because TAS-118 could not prove the superiority in overall survival time compared to S-1 monotherapy in GRAPE trial which was studied in Japan and Korea a few years ago. At this present, the superiority of the two major standard treatments is not clear, and so we conduct phase II trial (JCOG1407) which is compared GnP and mFFX for locally advanced PC and phase III trial (JCOG1611) which is compared GnP, mFFX and S-1/ OX/IRI for mPC. If the first line chemotherapy changes, the secondary treatment changes naturally. On the other hand, if a promising secondary chemotherapy emerges, the primary treatment will naturally be determined. With the good result of NAPOLI-1 study, we conducted the randomized phase II study which was compared nal-IRI/5FU/LV and 5FU/LV in Japanese populations. We will discuss the impression of nal-IRI for Asian patients together.
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz348/5583179 by Merck KGaA / Scientific Information Centre user on 26 October 2019
SYMPOSIUM 4 : NEW EVIDENCES OF CHEMOTHERAPY IN BILIARY TRACT AND PANCREATIC CANCERS AND INTRODUCTION THEM TO THE PRACTICE
SY4 1
New evidences of chemotherapy in biliary tract cancer
Do-Youn Oh Medical Oncology, Seoul National University Hospital, Korea There are huge unmet medical needs in biliary tract cancer. Biliary tract cancer is nonrare cancer in Asia especially in Korea. As a 1st-line chemotherapy, gemcitabine/cisplatin is current standard of care, and in 2nd-line setting, FOLFOX improved overall survival compared with best supportive care. Biliary tract cancer is a heterogenous group not only in primary origin but also molecular characteristics. Somatic alterations in the KRAS, TP53, CDKN2A, SMAD4, BAP1, ARID1A, PBRM1 and IDH1/2 have been reported. In recent study, 38.9% of biliary tract cancer cases harbor potentially targetable genetic alteration including FGFR1, FGFR2, FGFR3, PIK3CA, ALK, EGFR, ERBB2, BRAF, AKTS, IDH1, IDH2, CCND1, CCND3, MDM2, BRCA1 and BRCA. Targeting those molecular alterations are now being tried in clinical trials. Among them, targeting FGFR alteration especially FGFR2 fusion is far advanced in its clinical development, which is being followed by targeting mutant IDH1. This is era of immunotherapy in cancers. Mutant IDH inhibits HNF-4a to block hepatocyte differentiation and promote biliary cancer. A vaccine targeting mutant IDH1 induces antitumor immunity. Cholangiocarcinoma which harbor neoantigen by oncogene mutation could be candidate for adoptive transfer for TIL containing mutationspecific T cell. Anti-PD1 or PDL1 antibody has shown the promising antitumor efficacy in biliary tract cancer. PD1/PDL1 inhibitor with CTLA4 inhibitor or chemotherapy in combination with PD1/PDL1 inhibitor are under investigation. New drug development strategy including targeted agents and immuno-oncology might be enormously tested in biliary tract cancer. The integration of precision medicine might be one of key factors for the success of new drug development including targeted agents and immuno-oncology agents.
SY4 2
Precision Oncology for Pancreatic Cancer across the United States: R experience the Know Your Tumor V
Lynn M. Matrisian1, Edik M Blais2, Emily Lyons1, Cassadie Moravek1, Patricia Dearbeloa2, Subha Madhavan2,3, Jonathan R Brody4, Emanuel Petricoin2,5, Michael J Pishvaian2,6 1 Pancreatic Cancer Action Network, United States, 2Perthera, Inc, 3Georgetown University, 4Thomas Jefferson University, 5George Mason University, 6M.D.Anderson Cancer Center The Know Your Tumor initiative identifies pancreatic cancer patients across the USA eligible for molecular testing through the Pancreatic Cancer Action Network call center. Perthera, Inc obtains patient consent, coordinates molecular testing, convenes a virtual molecular tumor board, prepares a report with a ranked list of therapy options, and collects outcomes. More than 1800 patients have been enrolled from 49 states and more than 1100 reports have been delivered. DNA testing was primarily with the Foundation
Medicine panel of 324 genes and includes microsatellite instability (MSI). Therapy options include clinical trials, off-label treatments, or standard-of-care chemotherapy. Approximately one quarter (26%) of patients were identified with highly actionable (HA) alterations defined as molecular alterations for which a targeted therapy is indicated based on data in any cancer type. HA alterations include mutations in BRCA1/2, ATM, PALB2 and other DNA damage-repair genes indicating treatment with a PARP inhibitor, MSI-High with a PD-1 inhibitor, and alterations in RET, NTRK, BRAF, ALK, ROS, CDK4/6, FGF, and ROS with specific targeted agents. Patients treated in the advanced setting with HA alterations who received a molecularly-matched therapy (n ¼ 46) had a significant 1-year improvement in overall survival compared to those with HA alterations who had no molecularly-matched therapies (HR ¼ 0.42, p¼.0004, n ¼ 143) or those with no HA alterations (HR ¼ 0.34, p¼.000002, n ¼ 488). Progression-free survival for those receiving a molecular matched therapy as 2nd line or greater therapy (10.93 mos, n ¼ 38) was 2.4-fold greater than those with HA alterations and their best unmatched therapy (4.53 mos, p ¼ 0.01, n ¼ 84) and 2-fold greater than those without HA alterations (5.37 mos, p ¼ 0.01, n ¼ 288). These results provide evidence in a real-world setting that support the recent change in NCCN guidelines recommending tumor profiling for patients with advanced pancreatic cancer.
SY4 5
Second line chemotherapy for advanced pancreatic cancer patients in Japan
Tatsuya Ioka Dept of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute I would introduce the second-line chemotherapy for metastatic pancreatic cancer (mPC) in Japan recently. We have two standards of care for mPC patients with good performance status as the first-line chemotherapy. One is FOLFIRINOX or modified FOLFIRINOX (mFFX), and another is Gemcitabine (Gem) plus nab-paclitaxel (GnP). We usually choose GnP or Gem monotherapy for FOLFIRINOX or mFFX refractory patients, and we usually choose mFFX or S-1 monotherapy for GnP refractory patients as the second-line chemotherapy, because TAS-118 could not prove the superiority in overall survival time compared to S-1 monotherapy in GRAPE trial which was studied in Japan and Korea a few years ago. At this present, the superiority of the two major standard treatments is not clear, and so we conduct phase II trial (JCOG1407) which is compared GnP and mFFX for locally advanced PC and phase III trial (JCOG1611) which is compared GnP, mFFX and S-1/ OX/IRI for mPC. If the first line chemotherapy changes, the secondary treatment changes naturally. On the other hand, if a promising secondary chemotherapy emerges, the primary treatment will naturally be determined. With the good result of NAPOLI-1 study, we conducted the randomized phase II study which was compared nal-IRI/5FU/LV and 5FU/LV in Japanese populations. We will discuss the impression of nal-IRI for Asian patients together.
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz348/5583179 by Merck KGaA / Scientific Information Centre user on 26 October 2019
SYMPOSIUM 4 : NEW EVIDENCES OF CHEMOTHERAPY IN BILIARY TRACT AND PANCREATIC CANCERS AND INTRODUCTION THEM TO THE PRACTICE