Episode # 3 • 17 Jan 2025
Beyond First-Line Therapy: Treatment Strategies for Advanced Neuroendocrine Tumors
Few oncologists know neuroendocrine tumors from both sides of the exam table: first as a patient diagnosed during training, and now as the doctor treating them. This physician brings both perspectives to one pressing question: when a tumor progresses on a somatostatin analog, what comes next? On this episode of BackTable Tumor Board, Dr. Aman Chauhan, a medical oncologist at UCSF, interviews Dr. Mark Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, about treatment strategies for advanced neuroendocrine tumors beyond first-line therapy. They start with what progression on a somatostatin analog really means, how grade, Ki-67, primary site, and the pace of liver disease shape the next step, and why observation is sometimes the right call. Dr. Lewis explains how he sets expectations for PRRT after NETTER-1 and NETTER-2, including the small but real risk of secondary myelodysplasia and leukemia.
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Timestamps
00:00 - Introduction
02:22 - Progression on a Somatostatin Analog
05:34 - Tumor Biology, Grade, and Observation
12:51 - Somatostatin Analogs and Carcinoid Syndrome
18:50 - PRRT After NETTER-1 and NETTER-2
25:56 - Chemotherapy Versus Targeted Therapy
32:35 - The CABINET Trial and Cabozantinib
38:39 - Dosing and Toxicity of Oral Therapy
43:57 - Liver-Directed Therapy and Rebiopsy
48:08 - Future Trials and Alpha Emitters
50:47 - When to Stop Somatostatin Analogs
54:27 - Practice-Changing Trials and Sequencing Lessons
59:25 - Closing Remarks
Resources
- Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors (CABINET). N Engl J Med. 2025
- FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET (March 2025)
- Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors (NETTER-1). N Engl J Med. 2017
- Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide in newly diagnosed, advanced grade 2-3, well-differentiated GEP-NETs (NETTER-2). Lancet. 2024
- Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE). Lancet. 2026
- Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211). J Clin Oncol. 2023
- Everolimus for Advanced Pancreatic Neuroendocrine Tumors (RADIANT-3). N Engl J Med. 2011
- Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med. 2011
- Treatment of the Malignant Carcinoid Syndrome: Evaluation of a Long-Acting Somatostatin Analogue. N Engl J Med. 1986
- Moertel CG. Karnofsky Memorial Lecture: An Odyssey in the Land of Small Tumors. J Clin Oncol. 1987
- Lower or Standard Dose Regorafenib in Refractory Metastatic Colorectal Cancer (ReDOS, trial record)
- Dr. Aman Chauhan, UCSF Health physician profile
- Dr. Mark Lewis, Intermountain Health physician profile
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More about this episode
The conversation then turns to systemic therapy: where capecitabine and temozolomide still fit, the trade-offs of earlier targeted agents, and the inclusive design of the CABINET trial of cabozantinib in pancreatic and extra-pancreatic NETs. Dr. Lewis describes why an oral therapy matters for rural patients who cannot easily reach a center that offers PRRT, and both doctors share how they dose oral therapy and watch for early toxicity. They close with when to rebiopsy a disease that is changing, alpha emitters on the horizon, when to stop a somatostatin analog, and the sequencing mistake Dr. Lewis most wants listeners to avoid: doing something because you can rather than because you should.
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