Management of Metastatic Pancreatic Neuroendocrine Tumors Jonathan - - PowerPoint PPT Presentation

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Nov 06, 2022 332 likes •546 views

Management of Metastatic Pancreatic Neuroendocrine Tumors Jonathan R Strosberg, M.D. Associate Professor H. Lee Moffitt Cancer Center Amr Mohamed, M.D. Assistant Professor H. Lee Moffitt Cancer Center November, 2018 Case: Patient with

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Management of Metastatic Pancreatic Neuroendocrine Tumors

Jonathan R Strosberg, M.D. Associate Professor

H. Lee Moffitt Cancer Center

Amr Mohamed, M.D. Assistant Professor

H. Lee Moffitt Cancer Center

November, 2018

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Case: Patient with metastatic well-differentiated pancreatic neuroendocrine tumor

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Presenting symptoms

§ 73 year old male w presented with right hip pain, mild weight loss and difficulty controlled his blood sugars last December 2017 § X-ray was negative and MRI showed right labrum tear with multiple lytic lesions § CT scan performed

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CT CAP

Ø Pancreatic body and tail: solid mass measuring 6.5 cm Ø Liver: innumerable enhancing lesions Ø RP: extensive retroperitoneal lymphadenopathy Ø Bone: sclerotic lesions throughout the axial and proximal appendicular skeleton and lytic lesions L1, Rt femoral neck

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FDG-PET scan: Low level of hypermetabolic

activity throughout the known lesions

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GA-68

GA-68 showed strong somatostatin expression throughout the multiple known lesions

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Liver Biopsy (Rt Lobe)

§Neuroendocrine tumor (Positive synaptophysin, and Chromogranin) §Well differentiated, grade 2 §Ki-67: 8% (Intermediate grade=grade2) §Low Mitotic Index

Grade 2

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Diagnosis

§Metastatic pancreatic neuroendocrine tumor likely a glucagonoma (Elevated baseline glucagon level: 832)

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What is the next step of treatment?

(A) Debulking surgery (B) Embolization of liver lesions (C) Watchful waiting (D) Somatostatin analog

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Treatment

§ Pt was started treatment on started on Octerotide LAR 30 mg IM monthly § Disease remains stable x almost 2 years § Patient remains asymptomatic § Recent scans demonstrate stable pancreatic and bone lesions but increase in size of existing liver lesions and new liver lesions , bone lesions

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Follow up Scans:

§ Pancreatic mass relatively stable § Progressive of liver and bone metastases

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What is the next step?

(A) Embolization of liver lesions (B) Switch to another Somatostatin analog (lanreotide) (C) Everolimus (D) Sunitinib (E) Capecitabine/Temozolomide (F) 177Lutetium-dotatate

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Treatment Everolimus Sunitinib Temozolomide +Capecitabine

Phase III (RADIANT 3) III II (E2211) Patients # 207 86 144 Control arm Placebo Placebo Temozolomide alone Median PFS (mos) 11 vs 4.6 11·4 vs 5.5 22.7 vs. 14.4 Overall survival (mos) 44 vs 37.7 (HR 0.94; 95% CI, 0.73-1.2; P = 0.30) Not reached for either group (High number of censored events) Not reached vs. 38.0 (HR 0.41; 95% 0.21-0.82; P=0.01) Response rate (ORR) 5% 9% 33% Most common side effect Hyperglycemia Stomatitis, Diarrhea Rash HTN Nausea & vomiting Diarrhea Cytopenia Nausea & vomiting Diarrhea

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Sunitinib vs. Everolimus in pancreatic NETs

Comorbidity Favors sunitinib Favors everolimus

Hypertension

Cardiovascular disease

Bleeding diathesis

Risk of perforation/fistula

Diabetes

Underlying lung disease

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Role of Peptide Receptor Radiotherapy (PRRT) in Pancreatic NETs

§Approved both by EMA and FDA for advanced GEP-NETs §Phase 3 randomized data only in midgut NETs. §Advantages: Limited treatment course, long PFS, relatively low toxicity §Somatostatin-receptor (SSTR) expression is a predictive marker. §Early phase data suggesting higher response rates in non-midgut NETs (esp. pancreatic). §Consider as 2nd line therapy in patients with strong SSTR expression.

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The Rotterdam Experience 2000-2013

Brabander et al. Clin Cancer Res 2017;23:4617-4624

Median follow-up 78 months

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Objective Responses, PFS and OS

Primary site Total N PR +CR SD PD Median PFS and OS (mo’s) N N % N % N %

Midgut NET Non-PD PD

181 32 94 57 10 29 31 31 31 99 18 50 55 56 53 16 3 9 9 9 10 30 24 29 60 82 50

Pancreatic NET Non-PD PD

138 21 66 72 10 38 55 48 58 40 10 15 30 48 23 17 1 10 13 5 15 30 31 31 71 ND 71

Hindgut

12 4 33 6 50 1 8 29 ND

Bronchial

23 7 30 7 30 6 26 20 52

Other foregut

12 5 42 5 42 2 17 25 ND

Unknown primary

82 29 35 35 43 11 13 29 53

Total

443 174 39 192 43 53 12 29 63