Hi ,

Welcome back to the Oncology Insights Newsletter which fosters your continuous growth in oncology pharmacy practice

Last time you learned about driving vs following, sacituzumab govitecan withdrawal in bladder cancer, and overcoming an addiction to browser tabs

This week you'll learn about hypertension with anti-VEGF therapies, the unique-ness of belzutifan in kidney cancer, and losing yourself

Have a great week!

Kelley

🧠 IPS (Insight, Pearl, Sundry)

Insight

VEGF (vascular endothelial growth factor) inhibition is an important mechanism in the treatment of kidney cancer

It is also notorious for causing hypertension, and almost half of all adults in the US have hypertension, so the odds that your patient with kidney cancer has it are also high

Thankfully, hypertension at baseline does not always preclude the use of anti-VEGF therapy, particular the oral VEGF tyrosine kinase inhibitors (TKIs), such as axitinib

With proper blood pressure monitoring and management, TKIs can still be an effective option

Blood pressure needs to be stable before starting treatment and close monitoring throughout therapy can help us make quick modifications

Home blood pressure monitoring is likely to be more effective than when they are in clinic so teach patients how to get the best readings at home

There likely will also need to be a collaboration between the patient’s oncology and primary care teams to ensure they get the best management

In my experience, oncologists don’t want to manage blood pressure and PCPs don’t know the reason why their patient’s blood pressure is suddenly uncontrolled. We are in a great position to be that liaison.

Pearl

Like many diseases in recent years, the landscape of kidney cancer treatment has evolved dramatically, particularly because of the absence of conventional chemotherapy from treatment options

Unlike many other cancers where cytotoxic chemotherapy is a cornerstone of treatment, kidney cancer is an outsider because of its inherent resistance to these therapies

Thankfully, we have identified what does work in this disease - immunotherapy and targeted therapy

Immune checkpoint inhibitors like nivolumab and ipilimumab have become foundational in treating advanced renal cell carcinoma (RCC). By helping the immune system recognize and attack cancer cells, these therapies have helped patients live longer with this disease.

Although there aren’t as many targeted therapies in kidney cancer as there are in other disease (looking at you, lung cancer 👀), they still play a really important role in treatment by cutting off tumor blood supply (VEGF inhibitors) or jamming up cellular signaling (mTOR inhibitors)

Among the newer targeted therapies, belzutifan is a unique agent with distinct characteristics

It was initially approved in 2021 for a very rare subset of RCC (von Hippel-Lindau [VHL]) but the indication was expanded in late 2023

This drug works by inhibiting HIF-2α (hypoxia-inducible factor 2α), which is a transcription factor involved in oxygen sensing and cell growth signaling

Essentially, when there is too much HIF-2α around, it decides to hang out with its friend HIF-1β in the nucleus which triggers a block party 🥳 leading to cell proliferation, angiogenesis, and tumor growth

So belzutifan is a party crasher - it prevents 2α and 1β from hanging out and starting the party 👮‍♀️

Because of its unique mechanism, it has some unique toxicities, most notably hypoxia and anemia

Knowing these will help you remember the mechanism (or vice versa)

In the LITESPARK-005 study (quick study overview video):

🩸 Most patients had decreased hemoglobin (83%, with 33% being grade 3+) - the median time to onset was 29 days

🫁 15% of patients had hypoxia (10% grade 3) - median time to onset was 30.5 days

It causes anemia because HIF-2α is also involved in erythropoietin (EPO) synthesis, which is a hormone that regulates red blood cell (RBC) production. In studies, patients were treated with transfusions and erythropoiesis stimulating agents.

It causes hypoxia because HIF-2α is involved in the body’s response to low oxygen levels. In studies, O2 saturation was monitored before and during therapy, which is a challenge given that this is an oral medication so lots of education (and likely the purchase of a home O2 sat monitor)

The package insert has hold/dose modifications for both toxicities

Currently, it’s indicated in patients with VHL disease or RCC after progression on immunotherapy and a VEGF inhibitor, but it’s being studied in combination with immunotherapy and in earlier lines of therapy also

Sundry

What happens when you lose yourself?

Something might feel off but you can’t tell exactly what - it’s like a little blip in the matrix…making you pause and ponder but you can’t put your finger on it

No one wants to be lost, or feel out of alignment

How do you lose yourself? Are we able to detect when we’re heading in that direction?

It seems likely to be a slow burn in a different direction, one that may seem miniscule at the beginning (maybe not even noticeable if we’re not paying close attention) and moves farther away quicker over time, like on a log scale

At some point you look around and wonder how you got here

You lose yourself one tiny trade-off at a time. When you don’t have clear boundaries or your values well defined, it’s easy to blow past them; saying yes to things that don’t align or no things that do.

If you can lose yourself one small trade-off at a time, you can also rebuild yourself one small success at a time

They key word on both sides is SMALL

It doesn’t take much to turn the tide, which means we have to be paying attention more

This was inspired from writing by James Clear

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