GI Tumor Board 3/8/2018. Case #1 IDEA. Case #1 Question #1 What is the next step in management?

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1 GI Tumor Board Edward Kim George Poultsides Naseem Esteghamat Kenzo Hirose May Cho Alan Venook Arta Monjazeb Margaret Tempero George Fisher Andrew Ko Daniel Chang Thomas Semrad Sisi Haraldsdottir Case #1 70yo F without significant PMH presents w/3 months of diarrhea and RLQ abdominal pain CT: cecal mass with mesenteric adenopathy, no distant disease Colonoscopy: partially obstructing tumor in cecum biopsy positive for adenocarcinoma Undergoes right hemicolectomy. Surgical path: 8.5cm low grade adenocarcinoma pt3/pn2a 6/53 LN positive, negative margins, MSI high. Case #1 Question #1 IDEA 1. Test expanded RAS and BRAF 2. Treat with adjuvant FOLFOX for 3 months 3. Treat with adjuvant FOLFOX for 6 months 4. Treat with adjuvant CAPOX for 3 months 5. Treat with adjuvant CAPOX for 6 months 1

2 3m vs 6m Low risk High risk FOLFOX CAPOX Low risk High risk FOLFOX CAPOX 2

3 IDEA Clinical Consensus: Risk-based approach to adjuvant chemotherapy in stage III colon cancer Case #1 Question #2 In this patient with stage III colon cancer, would BRAF status change your approach to adjuvant therapy? 1. Yes 2. No Case #1 continued Patient completed 6 months of adjuvant FOLFOX with discontinuation of oxaliplatin after cycle 9 due to sensory neuropathy CT scan 2 months after completion of adjuvant FOLFOX reveals a 1.8cm liver lesion which on retrospect review may have been faintly present on preoperative imaging Molecular profiling reveals RAS wt, BRAF wt, MSI high Case #1 Question #3 1. Surgical resection of liver metastasis 2. Liver directed therapy (eg SIRT, RFA, SBRT) 3. FOLFIRI 4. PD 1 inhibitor 3

4 Case #1 Take Home Points In patients with T1 T3,N1 disease, consider 3 months of adjuvant therapy. Pre planned subgroup analysis showed non inferiority of 3 vs 6 months of adjuvant therapy. For patients with T4 or N2 disease, discuss risks and benefits of 3 vs 6 months of adjuvant therapy. Non inferiority was not met in this subgroup 3 months confers significantly less neurotoxicity Consider toxicity profiles when deciding between CAPOX AND FOLFOX Case #2 A 62yo M w/no significant PMH presents with 3 month history of epigastric pain with associated anorexia. CT reveals hypodense mass in pancreatic head with >180 0 encasement of the superior mesenteric artery EUS FNA confirms pancreatic adenocarcinoma. Case #2 Question #1 1. Start FOLFIRINOX 2. Start gemcitabine/nab paclitaxel 3. Radiation oncology consultation 4. Surgical oncology consultation 4

5 Case #2 Clinical Course Patient receives 6 months of gemcitabine/nab paclitaxel CT scans after 2 and 4 months of treatment showed stable disease Patient developed grade 3 sensory neuropathy and nab paclitaxel is discontinued during cycle 6 CT scan after 6 th month still showed stable disease and no evidence of distant disease Case #2 Question #2 1. Surgical resection 2. Chemoradiation 3. SBRT 4. Continue chemotherapy with gemcitabine alone 5. Continue chemotherapy but change regimen 6. Treatment break 5

6 LAP07 Assess OS with chemotherapy vs chemoradiotherapy in locally advanced pancreatic cancer with progression free disease after gemcitabine based therapy LAP07 Evaluate effect of Erlotinib on OS in locally advanced pancreatic cancer Gemcitabine vs Gemcitabine + Erlotinib Hammel, P et al JAMA. 315(17); Case #2 Clinical Course Patient elected to take a break from chemotherapy Subsequent imaging about 4 months later shows metastatic progression to the liver and peritoneum He continues to have symptomatic sensory neuropathy Case #2 Question #3 1. FOLFIRNOX 2. FOLFIRI 3. FOLFOX 4. 5FU/nanoliposomal irinotecan 6

7 NAPOLI 1 NAPOLI 1 OS Case #2 Take Home Points There is no standard of care best option for locally advanced pancreatic adenocarcinoma Both frontline regimens of FOLFIRINOX and Gem/nab paclitaxel are reasonable options based on extrapolation from randomized trial data in the metastatic setting Chemoradiotherapy has not been proven to improve OS compared to chemotherapy alone in locally advanced pancreatic cancer following gemcitabine based therapy Nanoliposomal Irinotecan in combination with fluorouracil extends survival in patients with metastatic pancreatic ductal adenocarcinoma who previously received gemcitabine based chemotherapy compared to fluorouracil. Case #3 63yo woman presents with fatigue and jaundice CT scan reveals biliary dilation and mass distally ERCP confirms a CBD stricture and brushings are positive for adenocarcinoma ECOG PS 0 7

8 Case #3 Question #2 1. Chemotherapy gemcitabine and cisplatin 2. Chemoradiation with capecitabine 3. Surgery Case #3 followup Patient undergoes whipple resection Pathology confirms a 2.5cm moderately differentiated extrahepatic cholangiocarcinoma 1/18 Lymph nodes are positive Negative margins Case #3 Question #2 1. Chemotherapy capecitabine 2. Chemotherapy gemcitabine and cisplatin 3. Chemotherapy with gemcitabine/capecitabine > chemoradiation with capecitabine 4. Chemoradiation with capecitabine BILCAP 8

9 BILCAP Future directions ACTICCA 1 adjuvant therapy for resected cholangio or GB cancer original design = gem/cis vs placebo > based on BILCAP > gem/cis vs capecitabine Primary endpoint DFS Case #3 Take Home Points Capecitabine improves median overall survival compared to surveillance in patients with biliary tract cancer following macroscopic complete resection Unclear whether multi drug regimens and incorporation of chemoradiation add benefit in the adjuvant setting Case #4 62 yo woman presents with upper GI bleeding EGD reveals a large ulcerative gastric mass positive for adenocarcinoma EUS reveals T3N1 disease Diagnostic laparoscopic evaluation with cytology of peritoneal washings is negative 9

10 Case #4 Question #1 1. Surgery 2. ECF 3. EOX 4. FOLFOX 5. FLOT 6. chemoradiation MAGIC Trial Perioperative Chemotherapy MAGIC > FLOT FLOT FLTO FTLO FTOL FOLT FOTL TFLO TFOL TLOF TLFO TOLF TOFL OLFT OLTF OTLF OTFL OFLT OFTL LFTO LFOT LTOF LTFO LOTF LOFT 10

11 FLOT4 Toxicity UK OE05 Trial of neoadjuvant chemo UK OE05 Trial of neoadjuvant chemo 11

12 Case #4 Clinical Course Patient received FOLFOX with perioperative intent Repeat imaging shows stable to slight improvement She undergoes surgical resection Pathology reveals a Tumor Regression Score of 3 = Poor response Minimum or no treatment effect; extensive residual cancer cells Case #4 Question #2 1. Adjuvant chemo same regimen as pre operative 2. Adjuvant chemo switch regimen to different from pre operative 3. No adjuvant therapy 4. Chemoradiation Case #4 Take Home Points FLOT chemotherapy is a new peri operative chemotherapy regimen option for gastric cancer Based on toxicity profile select patients carefully True benefit of adjuvant component of perioperative therapy remains unclear 12