Clinically important safety differences found among immune checkpoint inhibitors
medwireNews: A network meta-analysis has ranked the safety of immune checkpoint inhibitors (ICIs) in cancer treatment, with atezolizumab revealed to have the best general safety profile.
Atezolizumab had a pooled incidence for grade 1–5 adverse events (AEs) of 66.4% and 15.1% for grade 3 or 4 AEs. Next in line in terms of safety was nivolumab, with pooled incidences of 71.8% and 14.1%, respectively, followed by pembrolizumab (75.1% and 19.8%) and ipilimumab (86.8% and 28.6%). The safety profile of tremelimumab could not be assessed because only one eligible study was identified.
When these pooled incidences were integrated with subgroup and sensitivity analyses, nivolumab emerged as the safest ICI for patients, particularly those with lung cancer, having what Jun Ma (Collaborative Innovation Center for Cancer Medicine, Guangzhou, China) and co-researchers describe as a “narrow and mild toxicity spectrum.”
A recent meta-analysis reported that nivolumab, pembrolizumab, and atezolizumab have similar antitumor efficacy in lung cancer, highlighting the importance of investigating such safety differences between these drugs, say the researchers in The BMJ.
They identified 36 head-to-head phase II and III randomized controlled trials, including 15,370 participants, that compared different ICI drugs or doses and extracted data on treatment-related AEs. Subgroup analyses looked at specific treatment-related AEs and cancer types, while sensitivity analyses investigated the stability of the results.
Compared with conventional therapy, ICIs were mainly associated with pruritus, rash, diarrhea, colitis, hypothyroidism, hyperthyroidism, and pneumonitis. And there were specific differences in toxicities among the five ICIs investigated with, for example, atezolizumab associated with the highest risks for hypothyroidism, nausea, and vomiting, while tremelimumab was associated with the highest risks for rash, diarrhea, and fatigue.
Ma and colleagues were able to confirm previous reports that ICIs acting against CTLA-4 tend to have higher toxicities than those targeting PD-L1, and that it is generally safer to prescribe a single ICI on its own, rather than two ICIs or one ICI plus conventional therapy.
“ICI drugs act through distinct immunologic mechanisms and should not be regarded as one entity,” say Ma and colleagues. They believe that the results “have high validity and reliability,” and conclude that the “information will aid clinicians to manage life threatening treatment-related adverse events, optimise future trial design, and modify the prescribing of ICI drugs.”
By Catherine Booth
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