Updates and best practices in the management of gastric cancer - - PowerPoint PPT Presentation

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Updates and best practices in the management of gastric cancer - - PowerPoint PPT Presentation

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Updates and best practices in the management of gastric cancer Olatunji B. Alese, MD Gastrointestinal Oncology, Winship Cancer Institute of Emory University July 28, 2017 1 Incidence 3rd leading cause of cancer death globally; 723k

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Updates and best practices in the management of gastric cancer

Olatunji B. Alese, MD Gastrointestinal Oncology, Winship Cancer Institute of Emory University July 28, 2017

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Incidence

  • 3rd leading cause of cancer death globally; 723k deaths (lung - 1.59

million deaths, liver - 745k deaths)

  • Estimated 28,000 diagnoses (17,750 in men and 10,250 in women) in

2017

  • About 10,960 deaths (6,720 men and 4,240 women)
  • 1/3 arise in proximal stomach (cardia, GEJ)
  • Average age of onset – 55years

Globocan 2012 (IARC), Cancer facts and figures 2017 (ACS)

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Bad new s…

  • EGJ adenoCa has been increasing at 5-10% incidence annually since

the mid-1970s

  • Most rapidly increasing cancer in many Western countries
  • 5-6x increase in incidence of gastric cardia cancers in the US
  • optimal multimodality treatment for EGJ adenoCa has been difficult e.g.

lack of trials that focus on the EGJ

  • Etiology
  • Gastric tumors - H. pylori infection, chronic gastritis, and low acid production
  • EGJ tumors - obesity, high acid production, GERD, inversely associated with H.

pylori

Blot WJ, et al. JAMA. 1991;265(10):1287-1289.

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  • D1 Dissection
  • pericardial or perigastric LN
  • D2 Dissection
  • Celiac
  • Left gastric artery
  • Splenic artery
  • Hepatic artery
  • D3 Dissection
  • Para-Aortic/Iliac nodes

Minimum of 15 LNs required for staging

Anatomy

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Molecular subtypes of gastric cancer

Cancer Genome Altas Research Network. Nature.2014;513(7517):202-209.

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Perioperative/Adjuvant therapy…

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Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004.

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Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004.

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Baseline 1

Baseline characteristics

Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004.

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Chemotherapy related Toxicity

Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004.

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Chemotherapy related Toxicity

Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004.

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Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004.

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Advanced/Metastatic…

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Targeted Therapies In Advanced Gastric/GEJ Cancer

Pathway Agent Clinical Trial Randomization Patients MET Ornartuzumab METGASTRIC FOLFOX +/- ornatuzumab 800 Rilotumumab RILOMET ECX +/- rilotumumab 450 HER2 Pertuzumab JACOB XP-T +/- pertuzumab 780 Trastuzumab HELOISE XP-T (standard) vs. XP-T (high dose) 400 TDM-1 GATSBY TDM-1 vs taxane (2nd line) 412 Lapatinib TyTAN Paclitaxel +/- lapatinib (2nd line) 261 EGFR Panitumumab REAL-3 EOX +/- panitumuamb 574 Cetuximab EXPAND XP +/- cetuximab 904 Angiogenesis Ramucirumab REGARD Ramucirumab vs. BSC (2nd line) 355 Ramucirumab RAINBOW Paclitaxel +/- Ramucirumab (2nd line) 665 Immune therapy pembrolizumab, avelumab, durvalumab and atezolizumab Multiple early phase trials

  • Table courtesy of Manish Shah
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Targeted Therapies In Advanced Gastric/GEJ Cancer

Pathway Agent Clinical Trial Randomization Patients MET Ornartuzumab METGASTRIC FOLFOX +/- ornatuzumab 800 Rilotumumab RILOMET ECX +/- rilotumumab 450 HER2 Pertuzumab JACOB XP-T +/- pertuzumab 780 Trastuzumab HELOISE XP-T (standard) vs. XP-T (high dose) 400 TDM-1 GATSBY TDM-1 vs taxane (2nd line) 412 Lapatinib TyTAN Paclitaxel +/- lapatinib (2nd line) 261 EGFR Panitumumab REAL-3 EOX +/- panitumuamb 574 Cetuximab EXPAND XP +/- cetuximab 904 Angiogenesis Ramucirumab REGARD Ramucirumab vs. BSC (2nd line) 355 Ramucirumab RAINBOW Paclitaxel +/- Ramucirumab (2nd line) 665 Immune therapy pembrolizumab, avelumab, durvalumab and atezolizumab Multiple early phase trials

  • Table courtesy of Manish Shah
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ToGA Trial

3803 Pts Screened 810 HER2+ (22.1%)

  • IHC 3+
  • FISH +

594 Pts R a n d

  • m

i z e d 5FU or capecitabine + Cisplatin (n=290) 5FU or capecitabine + Cisplatin + trastuzumab (n=294)

Bang YJ, et al. Lancet. 2010;376(9742):687-697,

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ToGA Trial

  • Median Overall Survival
  • Chemotherapy: 11.1 mos
  • Chemo+traztuzumab: 13.8

mos

  • HR 0.74 (0.6-0.91, p=0.0046)
  • Median Progression Free Survival
  • Chemotherapy: 5.5 months
  • Chemo + traz: 6.7 months
  • HR 0.71(0.59-0.85,p=0.0002)

Bang YJ, et al. Lancet. 2010;376(9742):687-697,

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Beyond progression…

Makiyama A, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 93.

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Makiyama A, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 93.

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Palle J, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 94.

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Palle J, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 94.

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Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):717-726.

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KEYNOTE-012

Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):717-726.

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Best Overall Response, RECIST v1.1

KEYNOTE-012: Best Overall Response

Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):717-726.

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KEYNOTE-012

Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):717-726.

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Efficacy and safety of pembrolizumab (pembro) monotherapy in previously treated advanced Gastric Cancer (cohort 1)

Fuchs CS, et al. ASCO 2017. Abstract 4003.

KEYNOTE-059

Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003.

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KEYNOTE-059

Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003.

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KEYNOTE-059

Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003.

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KEYNOTE-059: Cohort 3

N=31 ORR 25.8% (11.9 – 44.6) CR 3.2% Median DOR NR (2.1 – 13.7+) Median PFS 3.3 mos (2.0 – 6.0) Median OS NR (9.2 – NE) 6 mo OS 72.9% 12 mo OS 61.7%

Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003.

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Nivolumab ± Ipilumumab in advanced chemo- refractory gastric, esophageal, or GEJ cancer

CheckMate 032

Janjigian YY, et al. J Clin Oncol. 2017;35(suppl): Abstract 2014.

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Nivolumab ± Ipilumumab in advanced chemo- refractory gastric, esophageal, or GEJ cancer

CheckMate 032

ORR: 12% vs. 24% vs. 8% PD-L1+: 19% vs. 40% vs. 23%

Janjigian YY, et al. J Clin Oncol. 2017;35(suppl): Abstract 2014.

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Targeted therapy in gastric cancer

Wadwa R, et al. Nat Rev Clin Oncol. 2013;10(11):643-655.

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Conclusions

  • Platinum-5FU backbone as frontline gastric/GEJ tumors; FLOT as new

standard of perioperative care

  • Trastuzumab is indicated in patients with HER-2 overexpression;

benefit in continuation beyond progression?

  • Promising activity for PD-1/PDL-1 inhibitors
  • Role of PDL-1 as biomarker is evolving
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Thank you