Barrett's Esophagus Icd 9 Code, Barrett's Esophagus Classification, Barrett's Esophagus Reversal
Esophagus cancer Critical review -...
Transcript of Esophagus cancer Critical review -...
Roma, 5 Febbraio 2016
Esophagus cancer Critical review
Fernando De Vita Oncologia Medica Seconda Università di Napoli
Esophagus cancer Hot topics from ASCO GI 2016
•INDUCTION CT BEFORE CRT (NEOSCOPE TRIAL) • CT+/-AFLIBERCEPT (MEGA TRIAL) • SCOPE-1 TRIAL UPDATE • NIVOLUMAB (CHECKMATE-32) • PEMBROLIZUMAB (KEYNOTE-28 TRIAL) • NIVOLUMAB (ONO-4538-07)
Esophageal and GEJ adenocarcinoma are different diseases from GC
EA GEJA GC
I II III
Etiology
GERD
H. pylori
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-
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-
+
+/-
+/-
+
-
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Lymphatic
Spread
Tumor heterogeneity Location Etiology Histology Geography Treatment Molecular characteristics
Dulak AM , Cancer Res 2012 TCGA ,2014 Nature
Esophagus cancer Induction CT before CRT
NEOSCOPE TRIAL
Study EA+EGJ
(%) Treatment R0
HR for OS
CROSS 75 Preop CRT 0.73
MAGIC 26 Perioperative CT 0.75
FFCD9703 75 Perioperative CT 0.69
Sjoquist na Preop CT 0.83
Sjoquist na Preop CRT 0.75
DATA FROM PHASE III TRIALS AND META-ANALYSIS
Esophageal adenocarcinoma The therapeutic scenario
pCR: periop CT: 2-7%; preop CRT: 20-25%
MAGIC vs CROSS
PRIMARY ENDPOINT: OS (3yrs)
592 pts
ESOPHAGEAL
EGJ I-III
ECF
TP+RT
S
S
ECF
ICORG 10-14/Neo-AEGIS Perioperative CT vs preop CRT
Perioperative CT or preoperative CRT?
Esophagus cancer Induction CT before CRT
Rapid start of treatment Fast improvement of dysphagia Increase of compliance of the following CRT Downstage: increase R0 and pCR ? Early treatment of systemic disease
RATIONALE FOR INDUCTION CT
Esophagus cancer Induction CT before CRT
pCR as surrogate endpoint
Baseline pts characteristics by study group
pCR 80%
No pCR 17.4%
Esophagus cancer Induction CT before CRT
The clinical scenario
Studies PZ INDUCTION CT PRIMARY
ENDPOINT
De Vita, BJC 2011
41 FOLFOX-4+
CETUXIMAB/ CETUXIMAB+RT
pCR
Ilson, Cancer 2012
55 IRI+CDDP/
IRI+CDDP+RT
pCR
Ajani, Ann Oncol 2013
126 FOLFOX-4+RT
FOLFOX-4/FOLFOX-4+RT pCR
Alberts, ASCO 2013
42 FOLFOX-4+RT
DOC/FOLFOX-4+RT pCR
Mukherjee, ASCO GI 2016
43 OX+CAP/OX+CAP+RT
OX+CAP/TP+RT pCR
Esophagus cancer Induction CT before CRT
NEOSCOPE TRIAL: pCR
Esophagus cancer Induction CT before CRT
The clinical scenario
Studies PZ INDUCTION CT PRIMARY
ENDPOINT pCR R0
De Vita, BJC 2011
41 FOLFOX-4+
CETUXIMAB/ CETUXIMAB+RT
pCR 27 80
Ilson, Cancer 2012
55 IRI+CDDP/
IRI+CDDP+RT
pCR 16 69
Ajani, Ann Oncol 2013
126 FOLFOX-4+RT
FOLFOX-4/FOLFOX-4+RT pCR
13 26
83 93
Alberts, ASCO 2013
42 FOLFOX-4+RT
DOC/FOLFOX-4+RT pCR
50 41
100 94
Mukherjee, ASCO GI 2016
43 OX+CAP/OX+CAP+RT
OX+CAP/TP+RT pCR
11.9 27.9
72 81
Esophagus cancer Induction CT before CRT
Ajani J A, Ann Oncol 2013
Esophagus cancer Induction CT before CRT
Ajani J A, Ann Oncol 2013
Esophagus cancer Induction CT before CRT
Toxicities: NEOSCOPE vs CROSS
Induction CT in esophagus cancer More is better?
NEOSCOPE Small underpowered explorative trial Imbalanced for N+ disease and site of tumor Higher than expected hematological toxicity
Esophagus cancer Which news from targeted therapy?
Woo J, Gastroenterol Rep 2015
Antiangiogenesis for esophagus cancer Is there a role?
VEGF negative
VEGF positive
VEGF predicts poor outcome in esophageal cancer
Shih CH, Clin Cancer Res 2000
Antiangiogenesis for esophagus cancer Is there a role?
MEGA TRIAL
Antiangiogenesis for esophagus cancer Is there a role?
Antiangiogenesis for esophagus cancer Is there a role?
Antiangiogenesis for esophagus cancer Is there a role?
Are these results unexpected?
Antiangiogenesis for esophagus cancer Is there a role?
Yoon HH, ASCO 2014
TRIAL I4T-MC-JVBT (NCT01246960)
Antiangiogenesis for esophagus cancer Is there a role?
Yoon HH, ASCO 2014
TRIAL I4T-MC-JVBT (NCT01246960)
Should adenocarcinoma of the esophagus and GEJ be treated in the same way?
Should adenocarcinoma of the esophagus and GEJ be treated in the same way?
GEJ
E
Pohl H, JNCI 2005
Dikken JL, EJC 2012
Should adenocarcinoma of the esophagus and GEJ be treated in the same way?
Dulak AM, Nature Genetics 2013
More A>C transversions at AA sites in genome of EAC vs GEJ
HER2 positivity more common in esophageal vs. GEJ/cardia tumors
Yoon HH, Clin Cancer Res 2012
Cunningham D, NEJM 2006
Treatment effect according to tumor site in MAGIC
Ychou M, JCO 2011
Treatment effect according to tumor site in FFCD 9703
Should adenocarcinoma of the esophagus and GEJ be treated in the same way?
Treatment effect by primary site
Antiangiogenesis for esophagus cancer Is there a role?
The therapeutic scenario
Anti-EGFR for esophagus cancer Is there a role?
Anti-EGFR for esophagus cancer Is there a role?
Anti-EGFR for esophagus cancer Is there a role?
REAL-3 EXPAND
Toxicity and treatment intensity Interaction of cetuximab with backbone regimen Lack of valid biomarker/inclusion of unselected pts
TREATMENT NIVOLUMAB
(CHECKMATE-32) NIVOLUMAB
(ONO-4538-07) PEMBROLIZUMAB
(KEINOTE-28)
E/GE/G (%) 15/53/31 100/0/0
(SCC) 100/0/0
(SCC+AD)
PD-L1 + not mandatory not mandatory mandatory
(44% PD-L1+)
TREATMENT LINES mostly 3rd line
mostly 3rd line
mostly 3rd line
GRADE ¾ AE (%) 17 29.2 17
ORR (%) 14 17.2 30
MED. DURATION OR (mo)
7.6 3 nr
MED.TIME TO RESPONSE (mo)
1.6 1.5 3.7
OS 36%
(12-mo) 12.1 mo ---
Early signals of immunotherapy efficacy in EC
Immunohistochemical staining for PD-L1 in human esophageal cancer
Overall survival of pts with esophageal cancer according to PD-L1 status
Ohigashi Y, Clin Cancer 2005
PD-L1 + PD-L1 -
PD-L1 positive pts have a poorer outcome than negative pts
Immune Checkpoint Inhibitors in EC Who Will Benefit?
PD-L1 as a prognostic marker
Immune Checkpoint Inhibitors in EC Who Will Benefit?
Intratumoral PD-L1 as a Predictive Marker
Setting Treatment Objective Response Rate, %
Unselected PD-L1+ PD-L1–
Solid tumors (n = 42) Nivo 21 36 0
Melanoma (n = 44) Nivo 32 67 19
Melanoma (n = 34) Nivo 29 44 17
Melanoma (n = 113) Pembro 40 49 13
NSCLC (n = 129) Pembro 19 37 11
HNSCC (n = 55) Pembro 18 46 11
Melanoma (n = 411) Pembro 40 49 13
CHECKMATE-032 TRIAL
Immune Checkpoint Inhibitors in EC Who Will Benefit?
Immune Checkpoint Inhibitors in EC Who Will Benefit?
Immune Checkpoint Inhibitors in EC Who Will Benefit?
Early signals of immunotherapy efficacy in EC: the therapeutic scenario
TREATMENT PZ (n) ORR (%) Med.TTP (mo) Med.OS (mo)
DOCETAXEL 49 16 2.5 8.3
FOLFIRI 38 29 3.7 6.4
IRINOTECAN 37 20 2.6 5.2
IRINOTECAN/ DOCETAXEL
49 20 2.7 8.9
PACLITAXEL 38 24 2.1 5.0
Second-line CT in advanced EC
TREATMENT NIVOLUMAB
(CHECKMATE-32) NIVOLUMAB
(ONO-4538-07) PEMBROLIZUMAB
(KEINOTE-28)
ORR (%) 14 17.2 30
MED. DURATION OR (mo)
7.6 3 nr
MED.TIME TO RESPONSE (mo)
1.6 1.5 3.7
OS 36%
(12-mo) 12.1 mo ---
Early signals of immunotherapy efficacy in EC: the therapeutic scenario
Can immunotherapy fulfill an unmet need in EC?
Can immunotherapy fulfill an unmet need in EC?
“A Journey of a Thousand Miles Begins with a Single Step”
Lau Tzu,6th century BC
Thank you for your attention