I wanted to do a full-blown post about Immunotherapy but there is so much stuff out there! However, I also wanted to break it down and perhaps see if I can pick up the what, when, why, where and how in regards to Neuroendocrine Cancer. It’s really difficult, not least because the picture is not clear and there is no general roadmap printed, let alone one for Neuroendocrine disease. Immunotherapy for NETs was discussed at ENETS 2017 in Barcelona. The presentation that sticks out was one given by Dr Matthew Kulke, a well-known NET Specialist in Dana Ferber Boston. My reaction to the presentation was one of ‘expectation management’ and caution i.e. it’s too soon to know if we will get any success and when we will get it. He also hinted it is more likely that any success will first be seen in poorly differentiated high-grade (grade 3b) Neuroendocrine Carcinoma (NEC). Dr Jonathan Strosberg also said similar in a post here. In fact, from below you will see that grade 3 is where the bulk of trial activity is (…..but read on).
So, what’s all the hype about Pembrolizumab (Keytruda)?
The title of this post includes ‘Pembrolizumab’ better and more famously known as ‘Keytruda‘. Before I talk about this trial called PLANET, it’s very useful to take a quick look at the history of Keytruda which was only really made famous after former US President Jimmy Carter was treated with it for metastatic melanoma. There was a lot of media hype surrounding what made his treatment successful as he was also given radiation for his brain tumours and his large liver tumour was removed by surgery. However, putting the hype and conjecture to one side, Keytruda’s CV is pretty impressive:
Pembrolizumab (Keytruda) is currently approved to treat:
- Hodgkin lymphoma in adults and children. It is used in patients whose disease is refractory (does not respond to treatment) or has relapsed after at least three other types of treatment.
- Melanoma that cannot be removed by surgery or that has metastasized (spread to other parts of the body).
- Non-small cell lung cancer that has metastasized. It is used:
- With pemetrexed and carboplatin as first-line treatment in patients with nonsquamous disease.
- As first-line treatment in patients whose cancer has the PD-L1 protein and does not have a mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene.
- In patients whose cancer has the PD-L1 protein and got worse during or after treatment with platinum chemotherapy. Patients whose cancer has EGFR or ALK gene mutations should receive Pembrolizumab only if their disease got worse after treatment with an FDA-approved therapy for these mutations.
- Squamous cell carcinoma of the head and neck that has metastasized or recurred (come back) in patients whose disease got worse during or after treatment with platinum chemotherapy.
- Urothelial carcinoma (a type of bladder cancer) that is locally advanced or has metastasized. It is used in patients who cannot be treated with cisplatin or whose disease got worse during or after platinum chemotherapy.
- Microsatellite instability-high (MSI-H) cancer that is metastatic and cannot be removed by surgery. It is used in adults and children for:
- Solid tumors that have gotten worse after other treatment or that cannot be treated with other therapies.
- Colorectal cancer that has gotten worse after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
MSI-H cancer has certain genetic mutations and may not respond to some types of treatment.
The most recent approval in May 2017 MSI-H disease is a very interesting development as it’s the US FDA’s very first approval on a tissue/site agnostic basis. You can read about this approval here. Cancers of the breast, prostate, thyroid, bladder, colon, rectum and endometrium are just some of the cancers that have been found to have these biomarkers and would be new possible targets for Keytruda. There’s a great article which explains this approval in an easy way – click here to read.
Other approvals are anticipated.
So what about NETs and NEC?
I found the following trials for high-grade NEC:
- currently recruiting Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma (Pembro NEC)
- currently recruiting A Study of Pembrolizumab in Patients With Neuroendocrine Tumors
- not yet recruiting Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas
- This trial is interesting. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors It’s a multiple cancer setup and includes several of the less common NET/NEC types including ‘Lung Carcinoid’, ‘Anal NEC’, ‘Gastic NEC’, ‘Pancreatic NEC’ ‘Esophageal NEC. Interesting because this is the drug combo that NEC patient Danielle Tindle has moved onto after Keytruda didn’t really work in the medium to long-term (see the Danielle Tindle story below). Looking at the list in the trial document, I’m thinking they might mean high-grade Lung Neuroendocrine rather than ‘carcinoid’. I could be wrong. It’s currently recruiting.
- I also have some evidence of the use of Pembrolizumab (Keytruda) by an Australian high-grade thymus patient – I posted something here (Danielle Tindle)
Please also see the wonderful work done by NET Research Foundation who are using their funds to explore the use of Immunotherapy in NETs – check out their update by clicking here.
So what about just plain old NETs?
This trial is quite exciting as it involves the use of Pembrolizumab in combination with Lanreotide for patients with non-resectable, recurrent, or metastatic well or moderately (sic) differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). i.e. most of us. It is not yet recruiting BUT the fact that a trial infrastructure is being put into place is very exciting. You can read about this trial by clicking here. (Please note the incorrect reference to ‘moderately differentiated’ – this is no longer used in the grading classification for Neuroendocrine Neoplasms).
What is Immunotherapy?
For those still wondering what cancer immunotherapy actually is, this is the most basic description I could find!
Immunotherapy – Hype or Hope?
If you’re on an Immunotherapy trial not listed here, please let me now so I can update the post. Thanks in advance.
Thanks for reading
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