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Highlights
UPDATES and NEWS
from the Gastrointestinal
Cancers Symposium
in San Francisco, CA, USA
Stomach
cancer
Highlights
Giordano D. Beretta
Oncologia Medica
Humanitas Gavazzeni Bergamo
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
First Line Therapy
Gastric Cancer
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Second Line
Trial
Treatment
OS (mo)
HR
Delta (mo)
AIO
2010
Irinotecan
BSC
4.0
2.4
0.48
+ 1.6
Kang et al
2012
Irinotecan/Docetaxel
BSC
5.3
3.8
0.65
+ 1.5
Cougar-2
2013
Docetaxel
BSC
5.2
3.6
0.67
+ 1.6
REGARD
2013
Ramucirumab
BSC
5.2
3.8
0.77
+ 1.4
Ramucirumab + Paclitaxel
Paclitaxel
9.6
7.3
0.80
+ 2.3
Apatinib
BSC
6.5
4.6
0.71
+2.1
Regorafenib
BSC
5.8
4.5
0.74
+ 1.3
RAINBOW
2014
Quin
2014
INTEGRATE
2015
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
ASCO GI 2016
ABS 01: Feng Bi et al
Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in
advanced gastric adenocarcinoma: A chinese Western Cooperative
Gastrointestinal Oncology Group study
Abs 4: Peter C. Enginger et al
Multicenter double-blind randomized phase II: FOLFOX + zivaflibercept/placebo for patients (pts) with chemo-naive metastatic
esophagogastric adenocarcinoma (MEGA)
ABS 05: Yoon-Koo Kang et al
A randomizefd, open-label, multicenter, adaptive phase 2/3 study of
trastuzumab emtansine (T-DM1) versus a taxane (TAX) in patients
(pts) with previously treated Her-2-positive locally advanced or
metastatic gastric/gastroesophageal junction adenocarcinoma
(LA/MGC/GEJC)
Abs 06: Dung T.Le et al
Safety and activity of nivolumab monotherapy in advanced and
metastatic (A/M) gastric or gastroesophageal junction cancer
(GC/GEC): results from the CheckMate-032 study
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
FOLFIRI vs FOLFOX7
Feng Bi ASCO GI 2016
Endpoint PFS
mFOLFIRI
n°54
mFOLFOX
n° 74
P-value
Med PFS
2.9 mos
4.2 mos
0.109
Med OS
9.9 mos
12.0 mos
0.431
DCR
59%
66.3%
0.850
Med OS*
11.0 mos
20.2 mos
0.030
*subgroup analysis of the pts who completed
both treatment lines per protocol (13 vs 17)
Conclusion: Ther was no significant difference in the PFS or DCR.
However, mFOLFOX followed by mFOLFIRI might have a better OS
Limitations
 Lack of funding: no sponsor, no CRO
 Small sample size, due to slow partecipation, early dropout and lost follow up
 More like a real clinical practice instead of clinical trial
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
ABS 01: Feng Bi et al
Prospective randomized phase II study of FOLFIRI versus
FOLFOX7 in advanced gastric adenocarcinoma: A chinese
Western Cooperative Gastrointestinal Oncology Group study
Abs 4: Peter C. Enginger et al
Multicenter double-blind randomized phase II: FOLFOX + zivaflibercept/placebo for patients (pts) with chemo-naive
metastatic esophagogastric adenocarcinoma (MEGA)
ABS 05: Yoon-Koo Kang et al
A randomizefd, open-label, multicenter, adaptive phase 2/3
study of trastuzumab emtansine (T-DM1) versus a taxane
(TAX) in patients (pts) with previously treated Her-2-positive
locally advanced or metastatic gastric/gastroesophageal junction
adenocarcinoma (LA/MGC/GEJC)
Abs 06: Dung T.Le et al
Safety and activity of nivolumab monotherapy in advanced and
metastatic (A/M) gastric or gastroesophageal junction cancer
(GC/GEC): results from the CheckMate-032 study
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Rationale for GATSBY study design
Trastuzumab +
capecitabine/Fluorouracil +
cisplatin
Standard of care for 1L
HER2-positive MGC/GEJC
based on the ToGA study
No established HER2targeted 2L regimen for
MGC/GEJC
T-DM1
Statistical considerations
Significantly improved OS
for patients with HER2positive MBC previously
treated with trastuzumab +
taxane
Preclinical activity in HER2positive GC models (both cell
lines and xenograft model)
OS (primary endpoint)
Assumption of 9 months median OS with T-DM1
vs 6 months with taxane
82% power for target HR=0.67
All T-DM1 2,4 mg/kg qw data were analyzed
T-DM1 3,6 mg/kg q3w will be analyzed
separately
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
45% asiatici
25% non precedente anti-HER2
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY
Study
Yoon-Koo Kang
ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Yoon-Koo Kang ASCO GI 2016
GATSBY
Study
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
GATSBY Study Conclusions
T-DM1 2.4 mg/kg qw did not show an efficacy
benefit over taxane for HER2-positive locally
advanced or metastatic GC or GEJC
No improvement in OS, PFS, ORR, or DoR with TDM1 in the ITT population or subgroups
T-DM1 was well tolerated
Rates of grade >3 were numerically lower with TDM1 vs taxane
Rates of AES, SAEs, fatal AES, and treatment
discontinuations due to AES were comparable
between arms
Yoon-Koo Kang ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Anti-HER2 Therapy for EGA IV
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Failures after Toga: why?
Is systemic chemo+T > targeted T-DM1?
Systemic chemo take care of low-level and
HER2- clones?
HER2 heterogenity?
Concomitant genomic events (eg MET amp,
PI3CA mt, RAS mut etc)
Combination targeted therapy?
Protein expression level
IHC3+/ISH+ vs IHC3+/ISH-?
Clonal evolution/selection/downregulation post 1L
therapy?
HER2 amlification LOSS after 1L therapy
Up to 35% lost HER2++ status after 1L
Daniel Catenacci discussion at ASCO GI 2016 Modified
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
ABS 01: Feng Bi et al
Prospective randomized phase II study of FOLFIRI versus
FOLFOX7 in advanced gastric adenocarcinoma: A chinese
Western Cooperative Gastrointestinal Oncology Group study
Abs 4: Peter C. Enginger et al
Multicenter double-blind randomized phase II: FOLFOX + zivaflibercept/placebo for patients (pts) with chemo-naive
metastatic esophagogastric adenocarcinoma (MEGA)
ABS 05: Yoon-Koo Kang et al
A randomizefd, open-label, multicenter, adaptive phase 2/3
study of trastuzumab emtansine (T-DM1) versus a taxane
(TAX) in patients (pts) with previously treated Her-2-positive
locally advanced or metastatic gastric/gastroesophageal junction
adenocarcinoma (LA/MGC/GEJC)
Abs 06: Dung T.Le et al
Safety and activity of nivolumab monotherapy in advanced and
metastatic (A/M) gastric or gastroesophageal junction cancer
(GC/GEC): results from the CheckMate-032 study
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
FOLFOX+/Aflibercept
Primary end-point PFS at 6
months
64 pts: 42-22
+ Esofagi 49 vs 24%
- Giunzioni 19 vs 48%
Inclusion criteria:
Histologically confirmed,
unresectable esophageal, GE
junction or gastric adenocarcinoma
PS<2
Exclusion criteria:
Prior chemotherapy (except perioperative or adjuvant completed
more than 1 year)
Squamous carcinoma
Peter C. Enzinger ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
N= 64
Arm A (N= 43)
Ziv aflibercept
Arm B (N21)
Placebo
P value
6-mos PFS
60.5 +/- 7.5%
57.1 +/- 10.8%
0.80
1-r OS
58.7 +/- 8.0%
55.1 +/- 11.3%
0.79
N=52
Major RR
22/36 (61.1%)
12/16 (75%)
0.33
95% CI 43.5-76.9
95% CI 47.6-92.7
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Peter C. Enzinger ASCO GI 2016
FOLFOX +/- Aflibercept
Oncologia Medica
Slide 11
Peter C. Enzinger ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Peter C. Enzinger ASCO GI 2016
Slide 12
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Peter C. Enzinger ASCO GI 2016
Progression-Free Survival<br />Ziv-aflibercept & HTN <br />
Oncologia Medica
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Peter C. Enzinger ASCO GI 2016
Overall Survival<br />Ziv-aflibercept & HTN
Oncologia Medica
Conclusions:
Peter C. Enzinger ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Antiangiogenesis for EGA IV
Daniel Catenacci discussion at ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Antiangiogenesis for EGA
Daniel Catenacci discussion at ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
ABS 01: Feng Bi et al
Prospective randomized phase II study of FOLFIRI versus
FOLFOX7 in advanced gastric adenocarcinoma: A chinese
Western Cooperative Gastrointestinal Oncology Group study
Abs 4: Peter C. Enginger et al
Multicenter double-blind randomized phase II: FOLFOX + zivaflibercept/placebo for patients (pts) with chemo-naive
metastatic esophagogastric adenocarcinoma (MEGA)
ABS 05: Yoon-Koo Kang et al
A randomizefd, open-label, multicenter, adaptive phase 2/3
study of trastuzumab emtansine (T-DM1) versus a taxane
(TAX) in patients (pts) with previously treated Her-2-positive
locally advanced or metastatic gastric/gastroesophageal junction
adenocarcinoma (LA/MGC/GEJC)
Abs 06: Dung T.Le et al
Safety and activity of nivolumab monotherapy in advanced and
metastatic (A/M) gastric or gastroesophageal junction cancer
(GC/GEC): results from the CheckMate-032 study
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab
Monotherapy
59 pts
Endpoint ORR
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab
Monotherapy
Dung T.Le
ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab
Monotherapy
Dung T.Le
ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab
Monotherapy
Dung T.Le
ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Immunogenicity in Esophagogastric Cancer
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
KEYNOTE-012: Gastric Cancer Cohort
only PD-L1 positive tumors were eligible
Presented By Yung-Jue Bang at 2015 ASCO Annual Meeting
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Presented By Yung-Jue Bang at 2015 ASCO Annual Meeting
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
Current Trials for Esophagogastric Cancer
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
February 7, 2016
AIOM post ASCO GI review
Roma 5-6 febbraio 2016
Oncologia Medica
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