Gastrico

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Elisa Giommoni

NOVITÀ E SEQUENZE

TERAPEUTICHE NELLE NEOPLASIE DEL TRATTO GASTROENTERICO SUPERIORE

Carcinoma Gastrico

Pisa, 20 settembre 2019

SODc Oncologia Medica AOU Careggi

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What’s new

1. Esophageal and GEJ Cancers (anoher disease) 2. Metastatic disease: Immunotherapy

3. Perioperative CT in operable GC (Not New!)

4. Patient’s selection for early stage

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Phase 3 KEYNOTE-181 Study (NCT02564263)

Presented By Takashi Kojima at 2019 Gastrointestinal Cancer Symposium

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Overall Survival (ITT)

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Summary and Conclusions

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Presented By Hirva Mamdani at 2019 Gastrointestinal Cancer Symposium

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Adapted by Salati, ESMO OPEN 2017

TAS-102

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First-line pembrolizumab, trastuzumab, capecitabine and oxaliplatin in HER2-positive metastatic <br />esophagogastric adenocarcinoma <br />Abstract #62

Presented By Yelena Janjigian at 2019 Gastrointestinal Cancer Symposium

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Slide 13

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Slide 16

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Pembrolizumab in G/GEJ Cancer

Presented By Josep Tabernero at 2019 ASCO Annual Meeting

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Combined positive score: number of PDL-1 positive

cells ( tumor, lymphocytes and macrophages) in relation to total tumor cells

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KEYNOTE-062: P+C vs C

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OS, ORR, and DOR for MSI-H Tumorsa

Presented By Yelena Janjigian at 2019 ASCO Annual Meeting

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CONCLUSIONS & FUTURE DIRECTIONS

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Regorafenib plus nivolumab in patients with advanced colorectal (CRC) or gastric cancer (GC): an open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO,

EPOC1603)

Study objective

To investigate the efficacy and safety of regorafenib + nivolumab in patients with advanced gastric or colorectal cancer

Hara H, et al. Ann Oncol 2019;30(suppl):abstr SO- 007

Regorafenib 80 mg/day (3-weeks on/1-week off) +

nivolumab 3 mg/kg q2w Key patient inclusion criteria

• Advanced gastric or colorectal cancer

• Previously treated (n=50)

3+3 design Regorafenib 80–160 mg/day (3-weeks on/1-week off) +

nivolumab 3 mg/kg q2w

Dose escalation Dose expansion

PRIMARY ENDPOINT

• DLT

SECONDARY ENDPOINTS

• PFS according to PD-L1 and TMB

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Key results

Hara H, et al. Ann Oncol 2019;30(suppl):abstr SO- 007

Regorafenib plus nivolumab in patients with advanced colorectal (CRC) or gastric cancer (GC): an open- label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603)

Gastric cancer Colorectal cancer

PD-L1 CPS ≥1 (n=10): mPFS 8.6 months PD-L1 CPS <1 (n=12): mPFS 2.9 months

HR 0.42 (95%CI 0.13, 1.42)

Time, months

PFS, %

100

80

60

40

20

0

0 3 6 9 12

Objective response rate 60% in CPS ≥1 vs. 42% in CPS <1

Time, months

PFS, %

100

80

60

40

20

0

0 3 6 9 12 15

PD-L1 CPS ≥1 (n=8): mPFS 4.6 months PD-L1 CPS <1 (n=14): mPFS 6.3 months

HR 1.01 (95%CI 0.29, 3.45)

Objective response rate 25% in CPS ≥1 vs. 36% in CPS <1

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*Top quarter (measured by oncomine tumour mutation load assay)

Key results (cont.)

Conclusion

In patients with advanced CRC or gastric cancer, combining regorafenib with nivolumab provided promising antitumor activity regardless of PD-L1 expression or TMB

Hara H, et al. Ann Oncol 2019

TMB (≥12.51* (n=6): NR

TMB (<12.51, (n=16): mPFS 5.77 months HR 0.49 (95%CI 0.11, 2.28)

Time, months

PFS, %

100

80

60

40

20

0

0 3 6 9 12

Objective response rate 83% in TMB-high vs. 38% in TMB-low

Time, months

PFS, %

100

80

60

40

20

0

0 3 6 9 12 15

TMB (≥20.11* (n=5): mPFS 4.6 months TMB (<20.11 (n=12): mPFS 5.4 months HR 0.82 (95%CI 0.17, 3.85)

Objective response rate 40% in TMB-high vs. 21% in TMB-low

Gastric cancer Colorectal cancer

Regorafenib plus nivolumab in patients with advanced colorectal (CRC) or gastric cancer (GC): an open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO,

EPOC1603)

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OPERABLE GASTRIC CANCER

ESMO Guideline

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PERIOPERATIVE CHEMOTHERAPY

MAGIC ECF-Surgery- ECF

5-yrs OS: 36%

FFCD-CF ECF-Surgery- ECF

5-yrs OS: 38%

AIO-FLOT

ECF-Surgery-ECF 5-yrs OS: 45%

2006 2011 2019

SURGERY alone

5-yrs OS: 23%

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Presented By Salah-Eddin Al-Batran at 2018 Gastrointestinal Cancers Symposium

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Presented By Se Hoon Park at 2019 ASCO Annual Meeting

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Interim results of a phase III trial involving adjuvant chemotherapy and/or chemoradiotherapy after D2- gastrectomy in stage II/III gastric cancer (GC)

Key results

DFS

Park SH, et al. J Clin Oncol

DFS probability

Time, months 1.00

0.75

0.50

0.25 0 0

180 180 178

6

170 175 172

12

161 159 156

18

149 151 146

24

137 145 140

30

130 142 137

36

124 140 135

42

118 135 134

48

116 133 132 S-1

SOX SOXRT

Median follow-up: 37 mo DFS events, n (%): 161 (30)

Test for superiority

S-1 vs. SOX HR 0.617, p=0.0157 S-1 vs. SOXRT HR 0.686, p=0.0572 Test for futility

Boundaries > –0.1774

Null hypothesis of HR=1 rejected

No. at risk

3-yr DFS rate, %

S-1 64

SOX 78

SOXRT 73

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Presented By Se Hoon Park at 2019 ASCO Annual Meeting

In patients with stage II/III node-positive, D2-resected gastric cancer, adjuvant SOX and SOXRT demonstrated longer DFS than S-1 alone

No additional benefit from CTRT

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ADJUVANT SETTING

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Study objective

To assess the prognostic and predictive impact of MSI in patients with gastric cancer

Methods

Data for patients with resectable gastric cancer (n=1522) were pooled from 4 clinical trials – MAGIC, CLASSIC, ARTIST and ITACA-S

The following data were collected: patient demographics (age, sex, and race), primary site (stomach vs. junctional), histotype (intestinal vs. other), T/N stage (7th TNM), treatment received (multimodal therapy vs. surgery alone) and MSI

Univariate and multivariate associations with DFS and OS were assessed

The predictive role of MSI according to treatment received was assessed overall and in the 2 clinical trials with a surgery alone arm (MAGIC and CLASSIC)

Pietrantonio F, et al. J Clin Oncol 2019

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Patients with MSI-high GC represent up to 10% of operable GC Elderly patients were diagnosed more frequently with MSI-high GC

MSI-high tumors are more often found in the stomach rather than the gastroesophageal junction, and in intestinal subtype

12-month SAR in MSI-high versus MSS/MSI-low subgroups: no differences - 33.0% and 35.9%, respectively (HR,1.01; 95% CI, 0.68 to 1.50; P = .947

Positive prognostic effect of MSI status was more pronounced in Asian than European patients (HR for DFS and OS, 2.83 and 2.97 v 1.26 and 1.15, respectively)

Pietrantonio F, et al. J Clin Oncol 2019

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In patients with resectable gastric cancer, MSI is an independent prognostic marker and should be considered as a stratification factor in future trials

Pietrantonio F, et al. J Clin Oncol 2019

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