KOL洞察报告丨神经内分泌肿瘤治疗的现状与挑战10406（英）_11页_1mb

报告摘要

KOL Insights on Neuroendocrine Tumors (NET)

Core Content Summary

Neuroendocrine tumors (NETs) are a diverse group of tumors that can be classified into gastroenteropancreatic (GEP-NETs) and lung/thymic NETs. The KOL highlights the following key points regarding the treatment and management of NETs in the US:

Distribution of NETs

Approximately 67% of diagnosed NETs are gastroenteropancreatic, while 33% are lung or thymic.
Well-differentiated NETs make up 90-95% of GEP-NETs, whereas poorly differentiated neuroendocrine carcinomas (NECs) are more common in lung NETs and tend to be more aggressive.

Early Stage Management

Early-stage patients typically undergo surgery as the first-line treatment.
A minority (5-10%) may receive pharmacological therapy as a bridge to surgery, especially if there are delays (e.g., during the pandemic).
Non-metastatic but unresectable patients may also be treated with medical therapy.

Relapse Rates

Local relapse in early-stage patients is around 15%, but this is highly dependent on the quality of the initial surgery.
Distant relapse in early-stage patients is 40%, with some variability across studies.
Patients who experience a local relapse have a 30-35% chance of progressing to distant relapse.

Metastatic Disease Treatment

First-line treatment for metastatic NETs includes somatostatin analogs (e.g., octreotide, lanreotide) for functional tumors, and radiographic response is often sought through PRRT (e.g., Lutathera) or chemotherapy (e.g., capecitabine/temozolomide) for pancreatic NETs.
Second-line options include PRRT, tyrosine kinase inhibitors (TKIs) such as everolimus, cabozantinib, and sunitinib (limited to pancreatic NETs).
Progression rates from first to second line are 90% or higher, with 5-10% of patients possibly discontinuing therapy.

Unmet Needs

Cure remains an unmet need in the metastatic setting.
Quality of life is a major concern due to long-term therapy and associated toxicities.

Key Therapies and Treatments

Somatostatin Analogs

Used in ~80-85% of NET patients.
Octreotide and lanreotide are both used interchangeably, though lanreotide is FDA-approved for tumor control.
Generic lanreotide is often unavailable due to supply chain issues, and the KOL’s institution uses branded lanreotide due to a contract with Ipsen.

Lutathera (PRRT)

Highly effective and well-tolerated, with good long-term outcomes.
Commonly used in second-line settings, and is fast becoming the treatment of choice after progression on somatostatin analogs.
Access has improved since initial approval, and supply chain issues are minimal now.

Alpha Emitter PRRT

Actinium-225 (RayzeBio/BMS) is the most advanced in Phase III trials.
ACTION-1 trial is nearing completion and may lead to FDA approval in the next 2-3 years.
Alpha emitters may offer superior efficacy compared to beta emitters like lutetium-177, but supply chain challenges may affect their availability.

Tyrosine Kinase Inhibitors (TKIs)

Everolimus, cabozantinib, and sunitinib are the main TKIs used.
Cabozantinib is preferred for extra-pancreatic NETs, while sunitinib is limited to pancreatic NETs.
Everolimus is associated with hyperglycemia and lung toxicity, while cabozantinib may cause hypertension.
Patient assistance programs are often used to mitigate high copays.

Immunotherapy (Keytruda, Opdivo, Yervoy)

Used primarily for poorly differentiated NECs, not well-differentiated NETs.
Immunotherapy is being explored in first-line settings for NECs, such as platinum-etoposide + atezolizumab.
Response rates are 10-20%, with modest improvements in progression-free survival.
No clear guidelines or large data sets exist for their use in NETs.

Pipeline Therapies

RYZ101 and PNT2003 are alpha emitter radiopharmaceuticals in development.
Actinium-based therapies are more advanced than lead-based ones, but supply chain limitations may hinder their widespread use.
Head-to-head comparisons and logistical factors (e.g., supply chain, cost) are critical for evaluating new therapies.

Financial and Access Challenges

Payer pushback is common for somatostatin analogs due to storage and administration costs.
Home health administration and mail-order pharmacies are suggested to reduce costs.
TKIs pose a financial burden for patients, often requiring patient assistance programs.

Genetic Testing and Counseling

Genetic counseling is more common in tertiary referral centers, especially for pancreatic, gastric, and lung NETs.
Approximately 15-20% of these patients are referred for genetic testing.
MEN1 is the most common genetic syndrome associated with NETs, though VHL and MEN2 are also considered.

Conclusion

The KOL emphasizes the need for more effective and curative therapies, as well as improved quality of life for long-term NET patients. While approved therapies are available and effective, logistical and financial challenges remain significant. Alpha emitter PRRT and immunotherapy are promising but require further data and approval before becoming standard of care.

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