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
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Oncologia Medica
First Line Therapy
Gastric Cancer
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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
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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
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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
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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
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Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
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Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
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GATSBY Study
45% asiatici
25% non precedente anti-HER2
Yoon-Koo Kang ASCO GI 2016
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Oncologia Medica
GATSBY Study
Yoon-Koo Kang ASCO GI 2016
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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
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GATSBY Study
Yoon-Koo Kang ASCO GI 2016
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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
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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
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Peter C. Enzinger ASCO GI 2016
FOLFOX +/- Aflibercept
Oncologia Medica
Slide 11
Peter C. Enzinger ASCO GI 2016
AIOM post ASCO GI review
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Oncologia Medica
Peter C. Enzinger ASCO GI 2016
Slide 12
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Oncologia Medica
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Peter C. Enzinger ASCO GI 2016
Progression-Free Survival<br />Ziv-aflibercept & HTN <br />
Oncologia Medica
AIOM post ASCO GI review
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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
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Oncologia Medica
Antiangiogenesis for EGA IV
Daniel Catenacci discussion at ASCO GI 2016
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Antiangiogenesis for EGA
Daniel Catenacci discussion at ASCO GI 2016
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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
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Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
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Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
AIOM post ASCO GI review
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Oncologia Medica
Nivolumab
Monotherapy
Dung T.Le
ASCO GI 2016
AIOM post ASCO GI review
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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
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Oncologia Medica
Nivolumab
Monotherapy
Dung T.Le
ASCO GI 2016
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Oncologia Medica
Nivolumab Monotherapy
Dung T.Le ASCO GI 2016
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Oncologia Medica
Immunogenicity in Esophagogastric Cancer
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Oncologia Medica
KEYNOTE-012: Gastric Cancer Cohort
only PD-L1 positive tumors were eligible
Presented By Yung-Jue Bang at 2015 ASCO Annual Meeting
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Oncologia Medica
Presented By Yung-Jue Bang at 2015 ASCO Annual Meeting
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Oncologia Medica
Current Trials for Esophagogastric Cancer
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Oncologia Medica
February 7, 2016
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Oncologia Medica