Clinical Brief – August 24th
The Memorial Sloan Kettering Cancer Center ran a study to profile the toxicity and tolerability of a pair of immunotherapies used to treat melanoma.
They found that 3 in 5 patients didn’t make it to their fourth dose because of side effects or cancer progression, but noted that patients may still benefit with less than four doses.
What are cancer immunotherapies?
Cancer immunotherapies are treatments designed to expose cancer to attacks by the immune system. Ipilimumab (Yervoy) was one of the first immunotherapies and was initially tested on melanoma.
Second generation cancer immunotherapies target a different component of the immune system. Nivolumab (Opdivo) is one such treatment, as are pembrolizumab (Keytruda), atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi).
I didn’t make up these names.
What did Sloan Kettering do?
The researchers looked at about 60 patients with melanoma to see how well they tolerated treatment with a combination of nivolumab + ipilimumab, or NIVO + IPI.
Patients were planned to get four doses of NIVO + IPI every three weeks, then switch to maintenance therapy with NIVO or pembrolizumab until “unacceptable toxic effects, disease progression, or complete tumor response”.
Just under 2 in 5 patients made it to their fourth dose, and most of these patients went on to receive maintenance therapy.
This left 3 in 5 patients who tolerated only three doses or less of NIVO + IPI. Reasons for stopping treatment were:
- 80% toxicity
- 11% cancer progression
- 2% death due to another cause
And the safety profile?
Rates of immune-related adverse events were high:
- Over 9 in 10 patients had one or more clinically significant event
- About 6 in 10 patients had a moderate or severe immune-related adverse event (Grade 3-4)
The most common moderate or severe immune-related adverse events were diarrhea and damage to the endocrine system (the part of the body that controls hormones like insulin). This might explain the 11% of patients who got elevated blood sugar levels.
Some of these immune-related adverse events can happen weeks after the treatment’s stopped. About 1 in 8 patients who stopped treatment early saw “clinically significant” immune-related adverse events more than 16 weeks after their discontinuation date.
“Most patients do not tolerate 4 doses of NIVO + IPI; however, 4 doses may not be required for clinical benefit.”
– Shoushtari AN, et al.
There’s no doubt immunotherapy is an important advancement for the treatment of cancer. But seeing how aggressive manufacturers are pushing their survival and tumor response claims, here’s a bit of a counter balance.
This is a small study, but the rates of immune-related adverse events are noteworthy. At 91% immune-related adverse event of any grade and 59% for Grade 3-4 events, we are coming close to the rates of adverse events one might see in trials with conventional targeted therapies.
Personally, I find studies such as this tell us what side effects to watch out for and how they can potentially be managed. Information about symptoms of side effects help with monitoring and knowledge about management strategies can help with financial planning.