Immunotherapy/TKI Combo Has ‘Significant Burden of Toxicity’

It's important for patients with cancer to be aware of the side effects they are experiencing after receiving immunotherapy with TKIs.

Combining immunotherapy with tyrosine kinase inhibitors (TKIs, drugs that work by targeting and blocking certain enzymes involved in cancer growth) to treat solid cancers can increase patients’ chance of experiencing moderate to severe side effects.

Recent research published in Frontiers in Oncology analyzed data from 72 clinical trials that investigated immunotherapy-TKI combinations. Results revealed a 56% incidence of grade 3 through 5 (moderate to fatal) side effects. Further, the study authors also noted that the use of a TKI run-in strategy — which is when TKIs are added after immunotherapy treatment — did not decrease side effects compared to giving the agents concurrently.

READ MORE: Immunotherapy May Lead to Chronic Side Effects

In an interview, study author, Dr. David O’Reilly, a medical oncologist at Beaumont Hospital in Ireland, discussed the study findings and what patients with cancer need to know about them.

CURE®: What kind of side effects can patients wait out and which are emergencies that need to be handled by the health care team immediately?

O’Reilly: That’s a good question — it's difficult. I suppose toxicities that we are always really concerned about would be things like shortness of breath, chest pain and diarrhea. All those things probably need to be seen pretty urgently, particularly for patients on immune checkpoint inhibitors, in which case those toxicities can be severe and difficult to manage.

Other things, I suppose maybe, like a rash, for the most part, can be mild. So maybe that's something that could wait, unless it's very severe, of course. Other people have more low-level toxicities going on for a long time, like tiredness, perhaps, which can probably wait for the next appointment. But of course, if there's any doubt or any question, probably the best thing is to get in touch with their doctors or nurses, then to make sure that they find the people they need as soon as possible.

Are there any certain patient comorbidities or characteristics that might affect their risk of certain adverse effects? And if so, should these be taken into account in treatment planning?

Yes, certainly. Of course, any patients with immune checkpoint inhibitors who've had a history of autoimmune disease and would be at higher risk of that flaring during treatment. For the most part, [immunotherapies] will be used with caution in this in this group. Depending on how necessary the treatment was, it may or may not be preceded, so that would probably be the main one to be considered.

With TKIs, the mechanism of toxicity is different. They're not necessarily immune-related, and so it might be a little bit more organ-specific. For example, if a person had a history of diarrhea due to maybe they have a short bowel, or had some previous surgery or something, they'd probably be at a higher risk of diarrhea, for example, with a TKI.

For the immune-related, advanced adverse events, it's a bit more clear, but probably for the other TKIs, it's more patient-specific.

What is the key takeaway of this research?

I think the key takeaways are, first of all, there's a very significant burden of toxicity that patients experience with this combination of treatments from our research. Over half of patients experience a high-grade toxicity, which is really striking, and I think it makes us need to make sure our patients are counseled appropriately.

The second thing is that the determinants of these toxicities are a little bit unclear and still require future research, although our work did not suggest that mitigating a run-in strategy was associated with a lower toxicity, this would require further research.

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