Updates and best practices in the management of gastric cancer

Transcription

1 Updates and best practices in the management of gastric cancer Olatunji B. Alese, MD Gastrointestinal Oncology, Winship Cancer Institute of Emory University July 28,

2 Incidence 3rd leading cause of cancer death globally; 723k deaths (lung 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) 2

3 Bad news 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):

4 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 4

5 Molecular subtypes of gastric cancer Cancer Genome Altas Research Network. Nature.2014;513(7517):

6 Perioperative/Adjuvant therapy 6

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

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

9 Baseline characteristics Baseline 1 Al-Batran S-E, et al. J Clin Oncol. 2017;35(suppl): Abstract

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

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

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

13 Advanced/Metastatic 13

14 Targeted Therapies In Advanced Gastric/GEJ Cancer Pathway Agent Clinical Trial Randomization Patients MET HER2 EGFR Angiogenesis Ornartuzumab Rilotumumab Pertuzumab Trastuzumab TDM-1 Lapatinib Panitumumab Cetuximab Ramucirumab Ramucirumab METGASTRIC RILOMET JACOB HELOISE GATSBY TyTAN REAL-3 EXPAND REGARD RAINBOW FOLFOX +/- ornatuzumab ECX +/- rilotumumab XP-T +/- pertuzumab XP-T (standard) vs. XP-T (high dose) TDM-1 vs taxane (2 nd line) Paclitaxel +/- lapatinib (2 nd line) EOX +/- panitumuamb XP +/- cetuximab Ramucirumab vs. BSC (2 nd line) 355 Paclitaxel +/- Ramucirumab (2 nd line) 665 Immune therapy pembrolizumab, avelumab, durvalumab and atezolizumab Multiple early phase trials - - Table courtesy of Manish Shah 14

15 Targeted Therapies In Advanced Gastric/GEJ Cancer Pathway Agent Clinical Trial Randomization Patients MET HER2 EGFR Angiogenesis Ornartuzumab Rilotumumab Pertuzumab Trastuzumab TDM-1 Lapatinib Panitumumab Cetuximab Ramucirumab Ramucirumab METGASTRIC RILOMET JACOB HELOISE GATSBY TyTAN REAL-3 EXPAND REGARD RAINBOW FOLFOX +/- ornatuzumab ECX +/- rilotumumab XP-T +/- pertuzumab XP-T (standard) vs. XP-T (high dose) TDM-1 vs taxane (2 nd line) Paclitaxel +/- lapatinib (2 nd line) EOX +/- panitumuamb XP +/- cetuximab Ramucirumab vs. BSC (2 nd line) 355 Paclitaxel +/- Ramucirumab (2 nd line) 665 Immune therapy pembrolizumab, avelumab, durvalumab and atezolizumab Multiple early phase trials - - Table courtesy of Manish Shah 15

16 ToGA Trial 3803 Pts Screened 810 HER2+ (22.1%) IHC 3+ FISH Pts R a n d o 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): , 16

17 ToGA Trial Median Overall Survival Chemotherapy: 11.1 mos Chemo+traztuzumab: 13.8 mos HR 0.74 ( , p=0.0046) Median Progression Free Survival Chemotherapy: 5.5 months Chemo + traz: 6.7 months HR 0.71( ,p=0.0002) Bang YJ, et al. Lancet. 2010;376(9742): , 17

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

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

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

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

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

23 KEYNOTE-012 Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):

24 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):

25 KEYNOTE-012 Muro K, et al. J Clin Oncol. 2015;33(suppl): Abstract 3. Muro K, et al. Lancet Oncol. 2016;17(6):

26 KEYNOTE-059 Efficacy and safety of pembrolizumab (pembro) monotherapy in previously treated advanced Gastric Cancer (cohort 1) Fuchs CS, et al. ASCO Abstract Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract

27 KEYNOTE-059 Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract

28 KEYNOTE-059 Fuchs CS, et al. J Clin Oncol. 2017;35(suppl): Abstract

29 KEYNOTE-059: Cohort 3 N=31 ORR 25.8% ( ) CR 3.2% Median DOR NR ( ) Median PFS 3.3 mos ( ) 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

30 CheckMate 032 Nivolumab ± Ipilumumab in advanced chemorefractory gastric, esophageal, or GEJ cancer Janjigian YY, et al. J Clin Oncol. 2017;35(suppl): Abstract

31 CheckMate 032 Nivolumab ± Ipilumumab in advanced chemorefractory gastric, esophageal, or GEJ cancer Janjigian YY, et al. J Clin Oncol. 2017;35(suppl): Abstract ORR: 12% vs. 24% vs. 8% PD-L1+: 19% vs. 40% vs. 23% 31

32 Targeted therapy in gastric cancer Wadwa R, et al. Nat Rev Clin Oncol. 2013;10(11):

33 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 33

34 Thank you 34