TY - JOUR
TI - Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event management algorithm in patients treated with adjuvant dabrafenib plus trametinib: Primary results of COMBI-APlus
AU - Atkinson, V.
AU - Robert, C.
AU - Grob, J.J.
AU - Gogas, H.
AU - Dutriaux, C.
AU - Demidov, L.
AU - Gupta, A.
AU - Menzies, A.M.
AU - Ryll, B.
AU - Miranda, F.
AU - Banerjee, H.
AU - Lau, M.
AU - Del Vecchio, M.
JO - EUROPEAN JOURNAL OF CANCER
PY - 2022
VL - 163
TODO - null
SP - 79-87
PB - Elsevier Ireland Ltd
SN - null
TODO - 10.1016/j.ejca.2021.12.015
TODO - B Raf kinase;  creatine kinase;  dabrafenib;  trametinib, adult;  adverse outcome;  arthralgia;  Article;  asthenia;  cancer adjuvant therapy;  cause of death;  chill;  creatine kinase blood level;  diarrhea;  disease exacerbation;  drug withdrawal;  fatigue;  female;  fever;  headache;  hospitalization;  human;  major clinical study;  male;  melanoma;  middle aged;  multicenter study;  nausea;  open study;  phase 3 clinical trial;  primary tumor;  rash;  recurrence free survival;  side effect;  treatment duration
TODO - Background: COMBI-AD demonstrated long-term benefit of adjuvant dabrafenib plus trametinib in patients with resected stage III BRAF V600E/K–mutant melanoma; however, 9% of patients permanently discontinued therapy due to pyrexia. COMBI-APlus evaluated whether an adapted pyrexia management algorithm reduces high-grade pyrexia and pyrexia-related adverse outcomes. Methods: COMBI-APlus is an open-label, phase IIIb trial evaluating an adapted pyrexia management algorithm in patients with high-risk resected stage III BRAF V600E/K–mutant melanoma treated with up to 12 months of adjuvant dabrafenib plus trametinib. Both drugs were interrupted for pyrexia (temperature ≥38°C) or the occurrence of pyrexia syndrome for suspected recurrent pyrexia. Treatment was restarted at the same dose once patients were symptom free for ≥24 h. The primary endpoint was the composite rate of grade 3/4 pyrexia, hospitalisation due to pyrexia, or permanent discontinuation due to pyrexia versus historical COMBI-AD control (20.0%; 95% confidence interval [CI], 16.3%–24.1%). Results: At data cutoff (5 October 2020), COMBI-APlus met its primary endpoint of significant improvement in the composite rate of pyrexia (8.0% [95% CI, 5.9%–10.6%]), with rates of 3.8% for grade 3/4 pyrexia, 4.3% for hospitalisation due to pyrexia, and 2.4% for discontinuation due to pyrexia. Estimated 12-month relapse-free survival was 91.8% (95% CI, 89.0%–93.9%). The most common adverse events were consistent with those in COMBI-AD, and 14.7% of patients permanently discontinued treatment due to adverse events. Conclusions: The adapted pyrexia management algorithm appears to reduce the incidence of severe pyrexia outcomes, enables patients to manage pyrexia at home, and helps patients remain on treatment. Clinical trial registration: NCT03551626. © 2021 The Authors
ER -