Final results, published by Ipsen, Monday 16th September.
The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.
However, despite increasing awareness, the non-specific nature of NET symptoms often leads patients to be seen by multiple specialists and to undergo various forms of testing before an accurate diagnosis is achieved. As a result, almost a third of people take at least five years to be diagnosed with NETs, contributing to poorer patient outcomes.
Many forms of NETs are indolent in nature and can develop in any part of the body, requiring multiple lines of therapy as people progress. Treatment options upon progression are often limited dependent on primary site of disease, resulting in challenges in identifying optimal care pathways specific to patients’ circumstances.
The CABINET Phase III study aimed to:
- determine whether cabozantinib S-malate (cabozantinib) can significantly improve progression-free survival (PFS) compared to placebo (no treatment) in patients with advanced pancreatic neuroendocrine tumours (well-differentiated NET) whose disease has progressed after prior therapy.
- determine whether cabozantinib can significantly improve progression-free survival (PFS) compared to placebo in patients with advanced non-pancreatic neuroendocrine tumors (well-differentiated NETs) whose disease has progressed after prior therapy. Non-pancreatic primaries include GI, lung, thymus, other, and unknown primary NETs.
Both functional and non-functional NETs were included.
While the study included Grade 3 NETs: poorly differentiated NECs (neuroendocrine carcinomas), MiNENs (mixed neuroendocrine non-neuroendocrine neoplasms) and Goblet Cell Carcinomas (GCCs) were excluded.
Further information on inclusion / exclusion criteria can be found on the study registration page at clinical trials.gov : direct link here.
- Cabozantinib is a chemotherapy drug known as a tyrosine kinase inhibitor (TKI), and it targets specific tyrosine kinase receptors, that when blocked, may slow tumor growth.
- A placebo is an inactive substance or treatment that looks the same as, and is given the same way as, the active drug or treatment being tested.
- PFS refers to Progression Free Survival, which is the time between treatment aimed at shrinking or controlling cancer starts, and the time at which signs show that it has started to grow again.
This study was designed to assess the role of cabozantinib, versus placebo, in treating NETs that had continued to grow (progressed), despite previous systemic treatment (other than somatostatin analogues).
A total of 298 patients were enrolled, in the US, at the time of this final analysis: 95 had pancreatic primary NET, 203 had a non-pancreatic primary NET.
The primary endpoint in each group was PFS confirmed by independent central review.
nb If disease progression was confirmed, patients were unblinded, and those found to be receiving placebo were permitted to cross over to open-label therapy with Cabozantinib.
The final analysis of data demonstrated a statistically significant reduction in the risk of disease progression (or death) for those receiving Cabometyx (Cabozantinib) compared to those receiving placebo. According to the press release, 77% of those with advanced pancreatic NET and 62% for people living with advanced non-pancreatic NETs – showed an extended PFS, compared to those on placebo. No information on impact on quality of life (QoL) was included in this summary.
However, the safety profile of Cabozantinib observed in each group was consistent with those found in other studies of the drug. Side effects include hypertension, fatigue, constipation and diarrhoea.
“People living with neuroendocrine tumors face many challenges, from securing a timely diagnosis to optimal treatment options which address the needs of the increasing number of people affected by this cancer worldwide,” said Teodora Kolarova, Executive Director, International Neuroendocrine Cancer Alliance. “These latest data reaffirm the possibilities of continuing scientific advancements in neuroendocrine tumors, offering the potential for new therapies which could significantly impact people’s everyday lives as they navigate this complex and life altering diagnosis.”
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In the meantime at ESMO 2024 – their Daily Report comments on “Novel Agents in NETs”
ESMO 2024 Promising results reported for novel anti-angiogenic agents for neuroendocrine tumours
Data presented at the ESMO Congress 2024 (Barcelona, 13–17 September) demonstrated the potential of novel anti-angiogenic agents for the treatment of neuroendocrine tumours (NETs).
Anti-angiogenic: A drug or substance that keeps new blood vessels from forming. In cancer treatment, anti-angiogenesis agents may prevent the growth of new blood vessels that tumors need to grow. Also called angiogenesis inhibitor.
NCT03600233: Study of CVM-1118 for Patients With Advanced Neuroendocrine Tumors CVM-1118 (TRX-818) is a new small molecule chemical entity being developed as a potential anticancer therapeutic by TaiRx, Inc. The objective of this phase 2 study was to further investigate the efficacy of CVM-1118 for patients with advanced neuroendocrine tumors.
Included in the study were those with confirmed advanced (unresectable and/or metastatic) neuroendocrine tumors that are well-differentiated, low or intermediate grade (WHO Grade 1 or 2) of pancreatic or gastrointestinal, or low/ intermediate grade of lung origin, that are refractory to standard of care therapy, or for whom no standard of care therapy is available.
The study enrolled 43 patients with advanced NETs who had progressed on prior standard of care.
With a median follow up of 12.8 months and, on average, three prior therapies, patients achieved median progression-free survival (PFS) of 10.5 months, which was longer than the 4–6 months for placebo groups reported in phase III trials of sunitinib (N Engl J Med. 2011) and everolimus (N Engl J Med. 2011). A subgroup analysis of CVM-1118 given alongside somatostatin analogue showed a median PFS of 22.4 months.
Dr Louis de Mestier from the University Paris-Cité, France, says, “The results must be interpreted with caution as patients with early progression in the study could have received concurrent somatostatin analogues, so the PFS of over 2 years in the combination treatment subgroup may have positively influenced the PFS of the whole cohort. However, these results clearly warrant further exploration in controlled clinical trials.”
Full report from ESMO Daily Reporter available here.