Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Atkinson, V.
Robert, C.
Grob, J.J.
Gogas, H.
Dutriaux, C.
Demidov, L.
Gupta, A.
Menzies, A.M.
Ryll, B.
Miranda, F.
Banerjee, H.
Lau, M.
Del Vecchio, M.
Περιοδικό:
EUROPEAN JOURNAL OF CANCER
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.ejca.2021.12.015
