The grey zone: cancer patients’ reported experiences for checkpoint inhibitors


By Sunalie Silva

13 Mar 2020

The first in-depth look at health-related quality of life (HRQOL) toxicity for people receiving checkpoint inhibitors highlights side effects that would be missed using traditional quality of life measures, investigators say.

The study relies on patient reported experiences with immune checkpoint modulator (ICM) treatment and is part of a broader series of investigations undertaken to develop a toxicity sub scale to measure the impacts of the therapy, and its related side effects (SE), on HRQOL.

Once validated the scale (the FACT-ICM) may be implemented in trials and clinical practice to evaluate HRQOL outcomes in patients receiving ICM, say the study investigators from Toronto.

“Given their mechanism of action immunotherapies create unique toxicities that are very different to traditional treatments like chemotherapy or targeted therapy, says lead investigator Dr Aaron Hansen, medical oncologist at Princess Margaret Cancer Center in Toronto Canada in an interview with the limbic.

“With every immunotherapy you’re getting some degree of T-cell or immune cell activation which can cause an anti-tumour effect – or, those cells can obviously cause inflammation in normal tissues and normal organs.”

Despite immunotherapy becoming a standard of care for many tumour types, relatively little is known about how treatment is actually experienced by patients, he adds, arguing that the traditional paradigm used for evaluating checkpoint inhibitor therapies – tumour reduction, progression free and overall survival, and grade three and four adverse event rates, isn’t enough.

“The traditional ways that we looks at checkpoint inhibitors in terms of efficacy show that we certainly are creating quite substantial changes for patients with this type of therapy.”

As more and more data were coming out, naturally the clinical impact on survival is what fuelled the story, he says.

“And that’s fair enough, but immunotherapy has such a broad range of side effects – it can affect any tissue or organ – and the piece that I think was potentially overlooked by a lot of the work was the very different ways in which immunotherapies could impact on quality of life”.

Grey zones of toxicity

Dr Hansen says purely ‘concrete’ measures of toxicity – the grade 3/4 adverse event rate for instance – miss the ‘grey zones’.

“It doesn’t tell you a lot about how the patient experiences that toxicity and I think fundamentally we were really trying to provide more information around that so that clinicians really understand the different experiences that patients can have,” he tells the limbic.

The single-centre qualitative study was based on focus groups and patient interviews.

Thirty-seven patients who were or had been treated with immune checkpoint modulators within the last year for a range of cancer diagnoses took part in one of three focus groups and 23 were interviewed individually.

Eight themes were identified: the heterogeneous nature of side effects experienced; living with uncertainty; reframing the meaning and severity of side effects; focus on survival, hope, and being positive; acceptance and adaptation; feeling supported; and faith in medical innovation.

According to Dr Hansen, the main categories of side effects identified support what has been reported from a variety of clinical trials in terms of type and frequency of side effects related to ICMs such as fatigue and gastrointestinal symptoms.

The study also picked up broader impacts of other types of side effects including taste disturbance, cough, and fever or chills, and those related to respiratory symptoms, metabolism and nutrition and cutaneous symptoms, the impact of which can often be underappreciated by clinicians and are typically not covered by general HRQOL tools such as the FACT-G and the EORTC QLQC30, he adds.

Cutaneous side effects like rashes or oedema caused some patients to avoid social situations and others described experiencing very sudden, painful whole body rashes that required hospitalisation.

Finally some participants reported experiencing spontaneous and painful burning sensations in the skin of their arms or feet.

Emotional impact 

On top of physical side effects, the study also highlighted the emotional toll that patients experience with many participants talking about their anxiety around the diversity and unpredictability of SEs and long-term health implications.

“What kind of side effects am I going to get down the road? Because all of this stuff is so new, so they don’t really know, right? What’s going to happen to me in another 15 years from all these drugs?” asks a patient.

But, on the other side, there is also social pressure to be positive about the treatment says Dr Hansen recounting some focus groups where participants who complained about ICM SEs were met with admonishment from other group members, with one stating, ‘at least you’re alive.’

“Just to be able to name a side effect or toxicity is probably not enough to really know what’s going on,” says Dr Hansen of what he’s taken from the study.

“That really does over simplify it. If you have a reductive approach like that to these side effects it’s going to be challenging to really know how tolerable this treatment is for a patient,” Dr Hansen says.

While additional longitudinal work needs to done to validate the findings Dr Hansen has already started to incorporate the quality of life measures into other immunotherapy trials being run at the Centre.

“The next stage is to take this tool out and broadly apply it to a whole number of different tumour types and checkpoint modulated therapies so that so that over time we can track their responses and really get a good sense of what their journey is like and how we can correlate this with their side effects.”

“What we’re hoping is that this might provide a little more art to the work that the science has really already started to build up.”

The full paper can be accessed here in Cancer Medicine.

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