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 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) Winship Cancer Institute | Emory University 2
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. Winship Cancer Institute | Emory University 3
Anatomy Minimum of 15 LNs required for staging •D1 Dissection •pericardial or perigastric LN •D2 Dissection •Celiac •Left gastric artery •Splenic artery •Hepatic artery •D3 Dissection •Para-Aortic/Iliac nodes Winship Cancer Institute | Emory University 4
Molecular subtypes of gastric cancer Cancer Genome Altas Research Network. Nature. 2014;513(7517):202-209. Winship Cancer Institute | Emory University 5
Perioperative/Adjuvant therapy… Winship Cancer Institute | Emory University 6
Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004. Winship Cancer Institute | Emory University 7
Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004. Winship Cancer Institute | Emory University 8
Baseline characteristics Baseline 1 Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004. Winship Cancer Institute | Emory University 9
Chemotherapy related Toxicity Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004. Winship Cancer Institute | Emory University 10
Chemotherapy related Toxicity Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004. Winship Cancer Institute | Emory University 11
Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract 4004. Winship Cancer Institute | Emory University 12
Advanced/Metastatic… Winship Cancer Institute | Emory University 13
Targeted Therapies In Advanced Gastric/GEJ Cancer Pathway Agent Clinical Trial Randomization Patients FOLFOX +/- ornatuzumab Ornartuzumab METGASTRIC 800 MET ECX +/- rilotumumab Rilotumumab RILOMET 450 XP-T +/- pertuzumab Pertuzumab JACOB 780 XP-T (standard) vs. Trastuzumab HELOISE 400 XP-T (high dose) HER2 TDM-1 vs taxane TDM-1 GATSBY 412 (2 nd line) Paclitaxel +/- lapatinib Lapatinib TyTAN 261 (2 nd line) EOX +/- panitumuamb Panitumumab REAL-3 574 EGFR XP +/- cetuximab Cetuximab EXPAND 904 Ramucirumab vs. BSC (2 nd line) Ramucirumab REGARD 355 Angiogenesis Paclitaxel +/- Ramucirumab (2 nd line) Ramucirumab RAINBOW 665 pembrolizumab, avelumab, Multiple early - Immune therapy - durvalumab and atezolizumab phase trials Table courtesy of Manish Shah Winship Cancer Institute | Emory University 14
Targeted Therapies In Advanced Gastric/GEJ Cancer Pathway Agent Clinical Trial Randomization Patients FOLFOX +/- ornatuzumab Ornartuzumab METGASTRIC 800 MET ECX +/- rilotumumab Rilotumumab RILOMET 450 XP-T +/- pertuzumab Pertuzumab JACOB 780 XP-T (standard) vs. Trastuzumab HELOISE 400 XP-T (high dose) HER2 TDM-1 vs taxane TDM-1 GATSBY 412 (2 nd line) Paclitaxel +/- lapatinib Lapatinib TyTAN 261 (2 nd line) EOX +/- panitumuamb Panitumumab REAL-3 574 EGFR XP +/- cetuximab Cetuximab EXPAND 904 Ramucirumab vs. BSC (2 nd line) Ramucirumab REGARD 355 Angiogenesis Paclitaxel +/- Ramucirumab (2 nd line) Ramucirumab RAINBOW 665 pembrolizumab, avelumab, Multiple early - Immune therapy - durvalumab and atezolizumab phase trials Table courtesy of Manish Shah Winship Cancer Institute | Emory University 15
ToGA Trial 3803 Pts Screened 5FU or capecitabine R + a Cisplatin 810 HER2+ (22.1%) n (n=290) • IHC 3+ d • FISH + o 5FU or capecitabine m + i Cisplatin z + e trastuzumab (n=294) d 594 Pts Bang YJ, et al. Lancet. 2010;376(9742):687-697, Winship Cancer Institute | Emory University 16
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, Winship Cancer Institute | Emory University 17
Beyond progression… Makiyama A, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 93. Winship Cancer Institute | Emory University 18
Makiyama A, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 93. Winship Cancer Institute | Emory University 19
Palle J, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 94. Winship Cancer Institute | Emory University 20
Palle J, et al. J Clin Oncol. 2017;35(suppl 4): Abstract 94. Winship Cancer Institute | Emory University 21
Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):717-726. Winship Cancer Institute | Emory University 22
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. Winship Cancer Institute | Emory University 23
KEYNOTE-012: Best Overall Response Best Overall Response, RECIST v1.1 Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):717-726. Winship Cancer Institute | Emory University 24
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. Winship Cancer Institute | Emory University 25
KEYNOTE-059 Efficacy and safety of pembrolizumab (pembro) monotherapy in previously treated advanced Gastric Cancer (cohort 1) Fuchs CS, et al. ASCO 2017. Abstract 4003. Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003. Winship Cancer Institute | Emory University 26
KEYNOTE-059 Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003. Winship Cancer Institute | Emory University 27
KEYNOTE-059 Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract 4003. Winship Cancer Institute | Emory University 28
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. Winship Cancer Institute | Emory University 29
CheckMate 032 Nivolumab ± Ipilumumab in advanced chemo- refractory gastric, esophageal, or GEJ cancer Janjigian YY, et al. J Clin Oncol. 2017;35(suppl): Abstract 2014. Winship Cancer Institute | Emory University 30
CheckMate 032 Nivolumab ± Ipilumumab in advanced chemo- refractory gastric, esophageal, or GEJ cancer 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. Winship Cancer Institute | Emory University 31
Targeted therapy in gastric cancer Wadwa R, et al. Nat Rev Clin Oncol. 2013;10(11):643-655. Winship Cancer Institute | Emory University 32
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 Winship Cancer Institute | Emory University 33
Thank you 34
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