Details

Autor(en) / Beteiligte

• Eggermont, Alexander
• Kicinski, Michal
• Suciu, Stefan

Titel

Association of selected (immune-related) adverse events and outcome in two adjuvant phase III trials, Checkmate-238 and EORTC1325/KEYNOTE-054

Ist Teil von

• Journal for immunotherapy of cancer, 2022-01, Vol.10 (1), p.e004272

Ort / Verlag

England: BMJ Publishing Group Ltd

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• In the CheckMate 238 study, any-grade paresthesia (2.7%), peripheral neuropathy (0.4%), and axonal neuropathy (0.2%) were included as well. [...]one may expect differences between the study results regarding the incidence of irAE, and their dispersion of occurrence over time. In the EORTC 1325/KN054 study, we refrained to produce a landmark analysis: only 52% (20%/37.3%) of the irAE occurred within 3 months. [...]kind of analysis would suffer from a dilution effect and be characterized by a low power: RFS events within 3 months could not be taken into consideration and a substantial number of patients (91=48% of 190) without irAE at 3 months developed later an irAE. For the nivolumab versus ipilimumab comparison, they did find a stronger treatment effect among those who had a TRAE which did not require an immunosuppressant treatment (HR=0.60), as compared with those who required an immunosuppressant treatment after a TRAE (0.87).1 This was consistent with our findings (HR 0.34 and 0.50, respectively) for the pembrolizumab vs placebo comparison.2 Lastly, in the Results section, the authors described the association which was evaluated in the ipilimumab group: ‘Moreover, as with nivolumab treatment, the presence or absence of select TRAEs reported between first study dose and 100 days after last study dose (time-varying covariate) was not associated with RFS in the ipilimumab group (HR 0.62; 95% CI 0.41 to 0.96; p=0.0301 (to account for multiple comparisons, p≤0.01).’ [...]the CheckMate 238 and EORTC 1325/KN054 studies both observed that the occurrence of irAEs was associated with a 30%–40% reduction in the of risk of recurrence or death among high-risk melanoma patients treated with adjuvant immune checkpoint inhibitors (ICIs).