Sun Young Rha, MD, PhDYonsei Cancer Center, Institute for Cancer Research, Yonsei University College of Medicine

Chemotherapy for metastatic gastric cancer

ESMO Asia GI Preceptorship 2018

Disclosures

• I have nothing to disclose for this presentation.

StomachColon and

rectumLung Liver Prostate Thyroid Bladder Pancreas Kidney

Gallbladder etc.

‘93-‘95 43.0 55.3 10.4 9.9 55.9 87.2 70.0 8.8 60.8 16.6

‘96-‘00 46.9 59.0 11.6 12.9 67.2 89.5 74.8 7.3 64.4 20.3

‘01-‘05 58.4 68.5 15.0 20.1 80.1 95.8 77.3 8.0 72.8 23.3

‘07-‘11 70.1 75.8 18.3 28.5 92.0 100.1 77.4 8.1 78.4 29.0

difference* 27.1 20.5 7.9 18.6 36.1 12.9 7.4 -0.7 17.6 12.4

0

20

40

60

80

100‘93-‘95 ‘96-‘00 ‘01-‘05 ‘07-‘11

%

Difference in global outcome:Five-year survival of major cancer sites in Korean: Male 1

1) Major cancer sites selected based on 2011 crude rates * difference in the cancer survival probability between '93~'95 and '07~'11, 2) Howlader N, Noone AM, et alSEER Cancer Statistics Review, 1975-2011, National

Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014, 3) Canadian Cancer Society, Statistics Canada and

Provincial/Territorial Cancer Registry. Canadian Cancer Statistics 2014, 4) Center for Cancer Control and Information Services, National Cancer Center, Monitoring of Cancer Incidence in Japan - Survival 2003-2005

report 2013, 5) Kyu-Won Jung, Young-Joo Won et al.. Cancer Res Treat 2015:47(2):127-141

5 year survival

USA (‘04-’10 )2 28.3%

Canada (‘06-’08)3 25.0%

Japan (‘03-’05)4 63.3%

Korea (‘08-’12)5 71.5%

GC

Mortality – to - incidence ratio

Most of countries: > 0.8

USA 0.66

Japan 0.43

Korea 0.35

Stage-oriented therapeutic strategy at Yonsei Cancer Center

Overall Survival 73.0%

• 5 year survival rate of Gastric Cancer Clinic• Year 1987 – 2007 (n= 10,620 resected cases)

Stage 1: 95.3%

Stage 2: 79.8%

Stage 3: 48.2%

Stage 4: 12.4%Systemic CTx

Suppportive care

EMR/ESD,minimal surgery

Stage II: S1 for 1year Stage III: Xelox for 6 M

pro

ba

bili

ty

Overall survival (months)

• Increasing EGC from national screening program• 61% EGC at 2015 (1922/3150)

Survival vs QoLNew drugs/Tx

QoL;minimal surgery

Improve survival; Neo/adjuvant Tx

Goals of palliative chemotherapy

� QoL maintenance: better PS

� Survival prolongation: longer PFS

� Conversion to surgery in oligometastasis: chance

for cure

Factors affecting outcomes: Difference between East vs West -> affects clinical trial outcome

1) Tumor characteristics -> affects statistical power

2) Host characteristics including pharmacogenetics/

pharmacogenomics and tumor microenvironment

-> toxicity profiles

3) Treatment and practice pattern

4) Cultural(Pts, Drs), regulatory and political issues

-> Careful interpretation of global clinical trials

-> Rational application in the clinical practice

Current trend in palliative treatment

Asia

(5-FU analogue + platinum doublet)

Europe

(ECF)

North America

(5-FU/cisplatin, DCF)

Adding trastuzumab in Her-2 + patients(1st line)

2nd line Tx with angiogenesis inhibitor

More doublet! No more epirubicin!

5-fluorouracil/platinum

(+/- docetaxel) 5-7 Mo

Paclitaxel or Irinotecan (3-5

Mo)

+ Trastuzumab in Her-2 + + Ramucirumab

Current treatment of metastatic GC (median 16-18months)

90 % 60-65% 30-40%

Supportive2nd line Tx (3rd - 4th line Tx)1st line Tx

Chemotherapy

Apatinib?

Pembrolizumab in

MSI-H/dMMR

� Ethnic differences: Asians vs Westerns

� Chemotherapy is the main Tx

� Doublet vs triplet

� Various doublets are similar

� Sequential treatment improved survival

� Angiogenesis inhibitor showed benefit in 2nd line and more

� Role of molecular targeted agents?

� IO showed the potential benefit

� New strategy: Conversion surgery, IP chemotherapy

Nivolumab,

Pembrolizumab in PD-L1 +

Monotherapy < Doublet << Triplet

Chemotherapeutics

+ Trastuzumab(2010)

+ Ramucirumab(2015)

Targeted/immune agents

Nivolumab/Pembrolizumab

(2017)

DocetaxelPaclitaxel

Doxorubicin/EpirubicinIrinotecan

Approved/available agents for mGC

5-FUS-1

Capecitabine

CisplatinOxaliplatin

Increasing efficacy

Increasing toxicity & decreasing

tolerability

1st line Tx

� Are there any superior regimens?

� Is the more the better?

� Any role of targeted agents? IO?

TherapyTarget molecule

Compound Study

1st line HER2 Trastuzumab ToGA （（（（Bang et al., 2010））））

VEGF Bevacizumab AVAGAST （（（（Ohtsu et al., 2011））））

HER2 Lapatinib LOGiC （（（（Hecht et al., 2013））））

EGFR Panitumumab REAL 3 （（（（Waddell et al., 2013））））

EGFR Cetuximab EXPAND （（（（Lordick et al., 2013））））

VEGF Bevacizumab AVATAR （（（（Shen et al., 2015））））

HGF Rilotumumab RILOMET-1 （（（（Cunningham et al., 2015））））

Met Onarutuzumab MET Gastric （（（（Shah et al., 2015））））

HER2 Perutuzumab JACOB（（（（Tabernero et al., ESMO2017））））

2nd , 3rd line HER2 Lapatinib TyTAN （（（（Bang et al., 2012））））

mTOR Everolimus GRANITE-1 （（（（Ohtsu et al., 2013））））

HER2 TDM-1 GATSBY （（（（Kang YK, et al., ASCO-GI 2016））））

PARP Olaparib GOLD （（（（Yung-Jue Bang et al., ESMO 2016））））

STAT3 BBI-608 BRIGHTHER

EGFR Nimotuxumab ENRICH

VEGFR Ramucirumab REGARD, RAINBOW

VEGFR Apatinib Li et al, ASCO 2015

Revised from Lordick F, et al: Cancer Treatment Reviews 40:692-700, 2014 Table2

positive

negative

positive

Trials with molecular targeted agents in mGC

Kim (2001)

FP (≤ F, ≤FAM)

FLAGS (2010)

FP (≤ SP)

AIO (2008)

FP (≤ FOLFIRI)

V325 (2005)

DCF (>FP)

ML17032 (2009)

XP (≈FP)

START (2014)

S1 (≤S1+DOC)

G-SOX (2016)

SOX (≈ SP>S1)

REAL2 (2008)/FLOT4(2017)

EOX≈ECF < FLOT

mDCF

FP

FOLFOX

SOX

XELOX

FOLFOX

SP

XP

FP

ECF

EOX

FLOT

JCOG 9912 (2009)

S1 (≈F, ≤CPT+P)

JCOG 9205 (2003)

F (≤ FP, ≤UTFM)

SPIRIT (2009)

SP (>S1)

GC0301/TOP002 (2011)

S1 (≤S1+CPT-11)

Evolving regimen based on Phase III Trials

> 1

2m

on

ths fo

r mG

C!!

ABSTRAT

JL Lee et al. Brit J Cancer (2008), 1–7

G3/4

ANC 6.8% 4.8%

Asthenia 9.1% 7.1%

Anorexia 6.8% 9.5%

Darrhoea 2.3% 0%

HFS 6.8% 0%

capecitabine S-1

• Randomised multicentre phase II study

• elderly (>or=65 years) chemo-naive

• Capecitabine (n=46) 1250 mg/m bid, D1-14,

q 3 weeks

or S-1 (n=45) 40mg/m bid D1-28, q 6 weeks

• ORR: 27.2% vs 28.9%

• Median TTP : 4.7 vs 4.2 months

• Median OS: 9.5 vs 8.2 months• Similar toxicities,

but RDI decreasing in capecitabine arm

S-1 vs. capecitabine

Trial Arm RR（％） PFS（Ｍ） OS（Ｍ）

ML17032 FP 5.0 9.3

Korean XP 5.6 10.5

Japanese XP 43.2 5.8 13.8

Retrospective SP 50 5.2 13.5

G-SOX SP 52.2 5.4 13.1

YamadaY et al

Ann Oncol 2014 SOX(100) 55.7 5.5 14.1

Korean RPII SOX(130) 40 6.2 12.4Kim GM, et al.

Eur J Cancer 2012 CapOX(130) 44 7.2 13.3

Shitara et al. Int J Clin Oncol 2012, YamadaY et al Ann Oncol 2014, Kim GM, et al.

Kim GM, et al. Kim GM, et al.

Kim GM, et al. Eur

EurEur

Eur J Cancer

J Cancer J Cancer

J Cancer 2012

20122012

2012

� Similar toxicity (more G1/2 HFS in Capecitabine containing arm)

Doublet is tolerable and better than monotherapy

Various combinations of platinum and 5-FU analogues are similar

� 5-FU ci -> oral 5-FU analogue

� FP -> SP/XP

� Cisplatin -> oxaliplatin

� Role of Taxanes

Doublets: FP = XP = SP = SOX = CapOX(Xelox)

ABSTRAT

Not published

• Her-2 negative mGC

• 2007-2016

• 1st line doublet Tx

• With efficacy information (PFS, OS)

• Retrospective analysis

• N=841

Comparing doublets in Yonsei Cancer Center (I)

Group Total Death Censored

mOS

(95% CI)

FOLFOX

169

(20.10%)

150

19

(11.24%)

19.600

(13.933, 24.467)

XELOX

286

(34.01%)

222

64

(22.38%)

19.700

(17.833, 22.833)

SP

321

(38.17%)

274

47

(14.64%)

20.733

(17.567, 22.967)

XP

65

(7.73%)

56

9

(13.85%)

16.267

(12.267, 22.500)

P-value = 0.4349

Oxaliplatin based(n=372, mOS 19.7m)

= Cisplatin based (n= 386, mOS 19.8m)

• Single center, randomized phase II study (NCT01283204)

Metastatic or

recurrent

gastric cancer

Metastatic or

recurrent

gastric cancerR

SP (S-1/Cisplatin)SP (S-1/Cisplatin)

FOLFOX6FOLFOX6

DF (Docetaxel/5FU)DF (Docetaxel/5FU)

TF (Paclitaxel/5FU)TF (Paclitaxel/5FU)

1

1

1

1

Stratification factor• Use of adjuvant platinum (Yes vs. No)

• ECOG performance status (0-1 vs. 2)

Comparing doublets (II): Taxane vs platinum

S-1 80mg/m2 bid D1-D14

Cisplatin 60mg/m2 D1

q3wks

S-1 80mg/m2 bid D1-D14

Cisplatin 60mg/m2 D1

q3wks

Oxaliplatin 100mg/m2 D1

5-FU 400mg/m2 bolus D1

5-FU 1200mg/m2 CI D1-2

LV 20mg/m2 D1

q2wks

Oxaliplatin 100mg/m2 D1

5-FU 400mg/m2 bolus D1

5-FU 1200mg/m2 CI D1-2

LV 20mg/m2 D1

q2wks

Docetaxel 75mg/m2 D1

5FU 1000mg/m2 D1-3

q3wks

Docetaxel 75mg/m2 D1

5FU 1000mg/m2 D1-3

q3wks

Paclitaxel 175mg/m2 D1

5FU 1000mg/m2 D1-3

q3wks

Paclitaxel 175mg/m2 D1

5FU 1000mg/m2 D1-3

q3wks

SP regimenSP regimen FOLFOX6 regimenFOLFOX6 regimen

DF regimenDF regimen TF regimenTF regimen

Study regimen

Study Profile

179 patients

randomized

179 patients

randomized

45 patients to

SP arm

45 patients to

SP arm

45 patients to

FOLFOX arm

45 patients to

FOLFOX arm

45 patients to

DF arm

45 patients to

DF arm

44 patients to

TF arm

44 patients to

TF arm

45 received

treatment

44 received

treatment

45 received

treatment

43 received

treatment

1 did notstart chemo

1 did notstart chemo

• Accrual period: Mar 2010 – May 2015(Discontinued due to poor accrual)

• Data cut-off: Dec 31 2015• Median follow-up duration: 12.4 months

Survival AnalysisIntent-to-treat analysis

SP: 14.7 (10.9-18.5)

FOLFOX: 11.3 (7.1-15.5)

5FU/DCT: 11.7 (9.1-14.3)

5FU/PCT: 10.8 (7.5-14.1)

OS

0 12 24 36 48 600

20

40

60

80

100

Surv

ivin

g (

%)

P=0.143

Time (months)

OS

Su

rviv

ing

(%

)P=0.431

Time (months)

0 12 24 36 48 600

20

40

60

80

100

Platinum 1st: 13.3 moTaxane 1st: 11.7 mo

All patients

0 12 24 36 48 600

20

40

60

80

100

Su

rviv

ing

(%

)

Time (months)

P=0.473

Platinum 1st: 13.3 moTaxane 1st: 14.4 mo

OS

Patients received

Both platinum and taxane

• Optimal sequence of chemotherapy was not known• Routine sequence: fluoropyrimidine and platinum � taxanes

• Reverse sequence: similar OSKim et al. In revision

Disease status

Treatment goal

Patient’s tolerability

Availability of treatment

Convenience: schedule

Things to consider in selecting optimal CTx

Log-rank p <0.001Hazard ratio: 1.47 (95% CI: 1.19−1.83)

Risk reduction: 32%

0

0

10

20

30

40

50

60

70

80

90

100

DCFCF

3 6 9 12 15 18 21 24

Pro

babili

ty (

%)

TTP DCF CF

Median (mo) 5.6 3.7

95% CI 4.9−5.9 3.4−4.5

Time (months)

Phase III, DCF vs. CF (V325): TTP

Van Cutsem, et al. J Clin Oncol 2006;24:4991-4997

1.9 mo ↑

Doublet vs Triplet

DCF q3w (n=221)

Docetaxel 75 mg/m2, D1

Cisplatin 75 mg/m2, D1

5-FU 750 mg/m2/day, D1-5

CF q4w (n=224)

Cisplatin 100 mg/m2, D1

5-FU 1000 mg/m2/day, D 1-5

OS DCF CF

Median (mo) 9.2 8.6

95% CI 8.4–10.6 7.2–9.5

1-year (%) 40.2 31.6

2-year (%) 18.4 8.8

Log-rank p=0.02Hazard ratio: 1.29 (95% CI: 1.04–1.61)

Risk reduction: 22.7%

0 3 6 9 12 15 18 21 24 27 30 33 360

10

20

30

40

50

60

70

80

90

100

DCFCF

Time (months)

Pro

babili

ty (

%)

Time (months)

DCF vs. CF (V325): OS

Van Cutsem, et al. J Clin Oncol 2006;24:4991-4997

0.6 mo ↑

0

20

40

60

80

100

Patients (%)

DCF (n=221)

CF (n=224)

*p<0.05*

* * *

DCF vs. CF (V325): G3/4 AEs

Roughly half of the pts were taken off treatment either due to treatment refusal or toxicity

Van Cutsem, et al. J Clin Oncol 2006;24:4991-4997

N ORR PFS/TTP OS

Docetaxel/irinotecan/oxaliplatin1 40 50% 6.5 mo 11.5 mo

Paclitaxel/cisplatin/5-FU2 45 51.2% 6.9 mo 12.7 mo

Docetaxel/cisplatin/S-13 34 87.1% 7.4 mo 22.6 mo

Docetaxel/cisplatin/5-FU/LV4 46 61% 8.9 mo 17.63 mo

Docetaxel/oxaliplatin/5-FU5 89 46.6% 7.66 mo 14.59 mo

Docetaxel/oxaliplatin/capecitabine5 86 25.6% 5.55 mo 11.30 mo

Docetaxel/cisplatin/5-FU6 31 33% 6.5 mo 12.6 mo

Modified DCF6 54 49% 9.7 mo 18.8 mo

Irinotecan/oxaliplatin/5-FU/LV7 63 33% 7.5 mo 12.1 mo

Paclitaxel/cisplatin/S-18 44 59.1% 9.4 mo 11.2 mo

Irinotecan/oxaliplatin/S-19 44 75% 10.2 mo 17.6 mo

Docetaxel/cisplatin/S-110 49 81% 8.7 mo 18.5 mo

Docetaxel/oxaliplatin/capecitabine11 55 43% 6.9 mo 13 mo

Docetaxel/oxaliplatin/S-112 44 54.5% 7.6 mo 12.0 mo

1Di Lauro L et al, Br J Cancer 2007;97:593, 2Hwang J et al, J Korean Med Sci 2008;23:586, 3Sato Y et al, Cancer Chemother Pharmacol 2010;66:721, 4Tomasello G et al, Gastric Cancer 2014;17:711, 5Van Cutsem et al, Ann Oncol 2015;26:149, 6Shah MA, et al, J Clin Oncol 2015;33:3874, 7Comella P, et al, Cancer Chemother Pharmacol 2009;64:893, 8Kim JY, et al, Cancer

Chemother Pharmacol 2011;67:527, 9Park SR, Ann Oncol 2011;22:890, 10Koizumi, W et al, Cancer Chemother Pharmacol 2014;69:407, 11Stein A et al, Acta Oncol 2014;53:39212Kim HS, et al. Gastric Cancer 2016;19:579,

Phase II Studies of Triplet Regimens

FLOT4 Study Design

Presented By Salah-Eddin Al-Batran at 2017 ASCO Annual Meeting

Doublet is preferred based on benefit-risk ratio

• For palliation– Symptom control in patients with severe symptoms

associated with high tumor burden

• For prolongation of survival – Patients with rapidly progressing disease

• For cure– Locally advanced unresectable or borderline

resectable disease

– Metastatic disease with the possibility of conversion

surgery

When needs high antitumor activity

Sequential Tx improves outcome!

Not overlapping MoA

No cumulative toxicity

Phase III Korean Study: Salvage Chemo + vs. BSC Alone

• Primary endpoint: OS

Patients with

metastatic gastric

cancer, 1-2 previous

chemo* regimens,

ECOG PS 0-1

(N = 202)

Treatment Treatment Treatment Treatment

continued until continued until continued until continued until

progression, progression, progression, progression,

toxicity, or toxicity, or toxicity, or toxicity, or

withdrawalwithdrawalwithdrawalwithdrawal

Docetaxel 60 mg/m2 on Day 1 q3w or

Irinotecan 150 mg/m2 q2w

(n = 133)

Best Supportive Care†

(n = 69)

Kang JH, et al. J Clin Oncol. 2012;30:1513-1518.

*Fluoropyrimidines and/or platinum agents.†Including analgesics, paracentesis, psychosocial care, nutritional support, blood transfusion, palliative radiotherapy, or nonprotocol BSC measures.

Phase III UK trial (COUGAR-02)• Primary endpoint: OS

Patients with

metastatic esophagus,

EGJ, or gastric

cancer, 1 previous

chemo regimens,

ECOG PS 0-2

(N = 168)

Treatment Treatment Treatment Treatment

continued until continued until continued until continued until

progression, progression, progression, progression,

toxicity, or toxicity, or toxicity, or toxicity, or

withdrawalwithdrawalwithdrawalwithdrawal

DocetaxelDocetaxelDocetaxelDocetaxel 75 mg/m2

on Day 1 q3w(n = 84)

BSC

(n=84)

Lancet Oncol 2014; 15: 78–86

Phase III Japan trial (WJOG 4007)Paclitaxel vs. Irinotecan

• Primary endpoint: OS

Patients with

metastatic gastric

cancer, 1 previous

chemo regimens,

ECOG PS 0-2

(N = 223)

Treatment Treatment Treatment Treatment

continued until continued until continued until continued until

progression, progression, progression, progression,

toxicity, or toxicity, or toxicity, or toxicity, or

withdrawalwithdrawalwithdrawalwithdrawal

Paclitaxel 80 mg/m2

on Day 1,8, 15 q 4wks

(n = 108)

irinotecan 150 mg/m2

on days 1 and 15, q 4 wks

(n=111)

J Clin Oncol. 2013;31:4438-4444.

� Types and frequency of toxicity

� Dose/exposure-toxicity/response relationship

� Monitoring and management of toxicity

Interstitial lung disease by gefitinib

ILD 3.2 ~ 5.8% vs 0.36%

Mortality 1.3 ~ 2.5% vs 0.06%

Safety issues

Ethnic differences Novel drug related toxicity profiles

20th century: predictable, common toxicities

20th centuryunpredictable, drug specific and

individualized toxicities

need special concerns and educationEsp. Immune-related toxicities

Toxicity from sunitinib in mRCC

Thrombocytopenia 32~37% vs 6.5~8%

HFS/stomatitis 11 ~ 13% vs 2~5%

HER2 negative

HER2 positive

5FU analogue +/-platinum

Irinotecan

5-FU analogue +/- platinum

XP/FP (SP)+Trastuzumab

Gastric cancer treatment guideline ver. 4. 2014 (additional information)

1st-line 2nd-line 3rd-line

90-95% 60-70% 40-50%

Paclitaxel/Docetaxel

Irinotecan

Ramucirumab

Paclitaxel+Ramucirumab

Palliative sequential treatments in Asia

Paclitaxel/Docetaxel

5-FU analogue +/- platinum

� Oral fluoropyrimidine monotherapy for elderly or poor PS

• Trifluridine/tipiracil (Lonsurf): trifluridine(a nucleoside analog) + tipiracil

(thymidine phosphorylase inhibitor, prevents rapid metabolism of trifluridine)

• approved by the U.S. FDA (Sep 2015) and EMA (April 2016) for refractory CRC

Recent trial with new chemotherapeutics in mGC

TAGS: a phase 3, randomised, double-blind study of trifluridine/ tipiracil (TAS-102) versus placebo in patients with refractory mGC

• PRIMARY ENDPOINT : OS

• SECONDARY ENDPOINTS: PFS, ORR, DCR, QoL, time to ECOG PS ≥2, safety

R

PD

Stratification

• ECOG PS (0 vs. 1)

• Region (Japan vs. rest of world)

• Prior ramucirumab (yes vs. no)

TFD/TPI (TAS-102) + BSC35 mg/m2 bid orally on D1–5 and 8–12

of each 28-day cycle

(n=337)

Key patient inclusion criteria

• Metastatic gastric/GEJ cancer

• ≥2 prior regimens

• Age ≥18 years (≥20 years in

Japan)

• ECOG PS 0/1

(n=507)PD

Placebo + BSC bid orally on D1–5 and 8–12

of each 28-day cycle

(n=170)

J Tabenero et al. WGIC 2018, Arkenau H, et al. ESMO 2018

LBA25: TAGS: a phase 3, randomised, double-blind study of trifluridine/ tipiracil (TAS-102) versus placebo in patients with refractory mGC

aITT population; bstratified log-rank testArkenau H, et al. Ann Oncol 2018;29(suppl 5):abstr LBA25

TFD/TPI(n=337)a

Placebo(n=170)a

Events, n (%) 244 (72) 140 (82)

mOS, months 5.7 3.6

HR (95%CI) 0.69 (0.56, 0.85)

One-sided p-valueb 0.0003

Two-sided p-valueb 0.0006

OS100

Time, months

0

0

80

60

40

20

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

337

170

328

158

282

131

240

101

201

71

161

60

124

47

102

40

80

34

66

29

51

17

40

12

31

10

22

9

16

7

11

5

9

2

7

2

7

0

7

0

4

0

4

0

4

0

3

0

1

0

0

0

12-month OS: 21%

12-month OS: 13%

OS

, %

No. at risk

TFD/TPI

Placebo

S-1/CDDP

IP PTX + S-1/PTX

Gastric cancer with

peritoneal metastasisR

1

2

Key Eligibility Criteria• No or <2mo prior chemo.

• No other distant metastasis

• No prior gastrectomy

• No frequent ascites drainage

Stratification• Institution

• Prior chemo. +/-

• Peritoneal meta.

P1/P2-3

Primary Endpoint• Overall survival

Secondary Endpoints• Response rate

• Safety

• Hironori Ishigami Japan intraperitoneal chemotherapy study group (JIPG), Cancer 2013, ASCO 2016

Phase III study of intraperitoneal paclitaxel plus S-1/paclitaxel compared with S-1/cisplatin in GC pts with peritoneal metastasis: PHOENIX-GC trial

Efficacy

Surv

ival R

ate

Time (Months)

HR=0.72 (95% CI: 0.49–1.04) P=0.081

Median OS, months (95% CI)

IP : 17.7 (14.7–21.5)

SP : 15.2 (12.8–21.8)

Disappeared Decreased No change IncreasedMantel

test

IP (n=38) 15 (39%) 18 (47%) 3 (8%) 2 (5%)P=0.001

SP (n=7) 0 (0%) 2 (29%) 3 (43%) 2 (29%)

• Evaluation of ascites by CT

� Slightly increased neutropenia, diarrhea and neuropathy

• Cytotoxic chemotherapy has a significant role in treatment

of mGC, including combination partner with MTA or IOs

• Proper subgroup selection might increase risk/benefit ratio:

clinical or molecular subgroups – not yet

• No homogeneous Tx: Ethnicity-based diverse strategy

• More understanding of host characteristics (PK/TME) for

personalized treatment

Summary