What is Everolimus (Afinitor)?

Manufactured by Novartis, this is a targeted biological therapy or more accurately, a mammalian Target of Rapamycin (mTOR) inhibitor. It works by stopping some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.  The drug is also approved for Renal Cell Carcinoma (RCC) and hormone-receptor-positive advanced Breast Cancer.

The drug is administered in oral form (tablet). The recommended dose for AFINITOR^® (everolimus) Tablets is one 10-mg tablet once daily but lower doses of 7.5-mg tablets, 5-mg tablets, and 2.5-mg tablets are available if dose adjustment is required for adverse events, drug interactions, and hepatic impairment.

Technical Information on Everolimus (Afinitor)

Read more on the manufacturer’s website – click here.  Specifically:

Important safety information and side effects:

Pancreatic NETs – click here.

Progressive, Non-functional GI and Lung Neuroendocrine Tumors (NET) – click here

Read a technical summary of Everolimus (Afinitor) – click here.

Who can get Everolimus (Afinitor)? 

The USA Food and Drug Administration approved everolimus (Afinitor, Novartis) for the treatment of adult patients with progressive, well-differentiated non-functional, neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease.

Europe Medicines Agency (EMA) approved the drug for pancreatic neuroendocrine tumours when the cancer cells are well- or (sic) moderately differentiated* and the cancer is progressing or unresectable.  Also approved for neuroendocrine tumours originating in the lungs or gut, when the cancer cells are well-differentiated and the cancer is metastatic or unresectable.

UK‘s drug approval NICE states that Everolimus is recommended as options for treating well- or (sic) moderately differentiated* unresectable or metastatic neuroendocrine tumours (NETs) of pancreatic origin in adults with progressive disease. Also as an option for treating well-differentiated (grade 1 or grade 2**) non-functional unresectable or metastatic NETs of gastrointestinal or lung origin in adults with progressive disease. the NICE recommendation also states that Everolimus is recommended only when the company provides it with the discount agreed in the patient access scheme.

* moderately differentiated is not a term included in the World Health Organisation classification system for Neuroendocrine Neoplasms – read more about this here.
** since approval, there is now a Grade 3 well-differentiated category, but it is not clear if the drug automatically becomes available for use on Grade 3 NETs. 

Other countries as per their own marketing authorisations and approvals.

The efficacy and safety of everolimus was demonstrated in the RADIANT trials:

RADIANT-1. This trial assessed the efficacy and safety of everolimus in patients with metastatic pancreatic NET

RADIANT-2.  This trial looked at everolimus in patients with low grade NET plus carcinoid syndrome.

RADIANT-3.  Mainly looking at comparing everolimus as a first line treatment in pancreatic NETs vs a later treatment line).

RADIANT-4. The RADIANT 4 trial was the first randomized study to show that everolimus is effective in patients with pulmonary NETs.

Are there any extant clinical trials for Everolimus?

Check out this link filtered for trials awaiting or recruiting using keyword “Everolimus” and “Neuroendocrine Tumors” – click here. Due to the vagaries of the Clinical Trials database, the filter isn’t perfect.  I carefully selected a few as I’ve seen these pop up in my feed plus mentioned a conferences:

1. Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients (COMPETE) – I wrote about this trial already and everolimus forms a combo approach – click here.
2. Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable NETs (TALENT)   I’ve previously written about Lenvatinib – click here

Disclaimer: Taking part in a clinical trial is a big decision and must be considered carefully in conjunction with your healthcare professionals and close family. Mention of any clinical trial on RonnyAllan.NET is not a recommendation to participate. 

Are there any patient support programmes for Everolimus?

Where applicable, yes – click here.

Summary

Everolimus remains a tool in the NET treatment arsenal and is also being used in combo treatment trials.  Read a technical summary of Everolimus (Afinitor) – click here.

Read about other targeted therapies for NETs:

1.  Sunitinib (Sutent) – Read here.

2. Surufatinib for Neuroendocrine Cancer (SANET) – Still in clinical trial but is close to approval.  Read here

Disclaimer.  Ronny Allan has received no financial payment from Novartis for producing this post and the content does not constitute a recommendation to use any of their products.