Hi ,

Welcome back to the Oncology Insights Newsletter which helps you learn oncology, and other nuggets, as you progress in your oncology career. 

Last time you learned about crushing oral chemo and dosing of pegfilgrastim and chemo in children

Today you'll learn about GLP-1 agonists making their way into oncology, lorlatinib toxicity pearls, and policies for pregnant staff

Have a great week!

Kelley

🧠 IPS (Insight, Pearl, Sundry)

Insight

There was an interesting abstract presented at the recent ASCO meeting - interesting because GLP-1 agonists have been a hot topic lately outside the oncology world and now they are making their way to our side of the world

Abstract #10508 did a retrospective review of patients with a BMI of 35+ who had been on GLP-1 agonists continuously, or clinician follow up for the non-GLP-1 groups, for at least 1 year

They compared:

👉 Bariatric surgery vs no intervention

👉 GLP-1 agonists vs no intervention

👉 GLP-1 agonists vs bariatric surgery

They were looking at how many obesity-related cancers occurred (primary) and the risk of all cause mortality (secondary). They found:

💡 Both GLP-1 agonist use (HR 0.61; 95% CI 0.46 - 0.81) and bariatric surgery (HR 0.78; 95% CI 0.67 - 0.91) had a lower risk of obesity-related cancers compared to no intervention

💡 There was no difference in the risk of an obesity-related cancer between those on GLP-1 agonists or those that had bariatric surgery (HR 0.99; 95% CI 0.87 - 1.13)

💡 Both GLP-1 agonist use (HR 0.5; 95% CI 0.40 - 0.62) and bariatric surgery (HR 0.859; 95% CI 0.77 - 0.96) were associated with lower all cause mortality compared to no intervention

Thought provoking about the prevention of cancer in our obese patients. This suggests that controlling obesity, either through surgery or drug therapy, reduces cancer and mortality risk.

Pearl

Because oncology studies generally don’t enroll huge amounts of patients (hundreds compared to thousands in cardiology) and many don’t have long term follow up, getting signals about toxicities can be a challenge. We often learn about toxicities after a drug is approved when it starts being used in large numbers of patients.

That’s why the updated safety analysis of the CROWN trial caught my attention. This 5 year update of lorlatinib vs crizotinib in ALK+ lung cancer was presented at ASCO this year and skillfully summarized at a recent oncology pharmacy event by Kevin Chen.

For background, CROWN was a phase 3 open label study in newly diagnosed ALK+ non-small cell lung cancer. Patients were randomized to either lorlatinib or crizotinib and the primary outcome was progression-free survival (PFS).

Lorlatinib showed impressive results with a median PFS that hasn’t been reached yet compared to 9.1 months with crizotinib 😳

Unfortunately, lorlatinib is not a fun drug to take. About 2/3 of patients had a grade 3/4 adverse event, although only 5% discontinued therapy due to them, which is surprising

Changes in cholesterol were the highest incidence, and they are difficult to treat - you’ll have to dust off those primary care skills if you’re managing these patients 😅

The weight gain seen is impressive. Think about your weight and what a 20% or more gain would do - you would need a whole new wardrobe

Very concerning for patients are the mood, cognitive, and psychotic effects. Here are some examples of real patient reports from Kevin’s practice:

• A patient seeing ants crawling on the wall 
• A young mother forgetting to pack her kids lunches a few times a week
• A patient’s spouse sharing privately with team that the patient’s mood changes have become problematic

There is a great figure (#1) in this article that outlines when toxicities occur

Take a look at your clinic and identify which patients are on lorlatinib and how they are tolerating it. I bet there are interventions you can make to improve their quality of life.

Sundry

A client recently shared about challenges she faced in her oncology role while pregnant, which got me thinking… 🤔

Do you have a formal policy at your institution that addresses how to manage pregnant employees that come into contact with hazardous drugs?

Share your answer in this LinkedIn poll

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