Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event (AE) management algorithm in patients (pts) treated with adjuvant dabrafenib plus trametinib (dab plus tram): Primary results of COMBI-APlus
Authors
Atkinson, V.Robert, C.
Grob, J. J.
Gogas, H.
Dutriaux, C.
Demidov, L. V.
Gupta, Avinash
Menzies, A. M.
Ryll, B.
Miranda, F.
Banerjee, H.
Lau, M. R.
Del Vecchio, M.
Affiliation
Princess Alexandra Hospital, University of Queensland, Greenslopes, Brisbane, QLD, Australia;Issue Date
2021
Metadata
Show full item recordAbstract
Background: The long-term benefit of adjuvant dab + tram in pts with resected stage III BRAF V600E/K–mutant melanoma was demonstrated in COMBI-AD where AEs led to permanent discontinuation of dab + tram in 26% of pts, most often due to pyrexia (9%). The COMBI-APlus trial (NCT03551626) is designed to evaluate whether an adapted pyrexia management algorithm could reduce high-grade pyrexia and other pyrexia-related adverse outcomes, such as treatment cessation and hospitalization. Methods: COMBI-APlus is an open-label, Phase IIIb trial evaluating an adapted pyrexia management algorithm in pts with high-risk resected stage III BRAF V600E/K–mutant melanoma treated with 12 mo of adjuvant dab + tram. In the adapted algorithm, both dab and tram were interrupted promptly at the onset of pyrexia (temperature ≥ 38°C). In the event of suspected recurrent pyrexia, treatment may be interrupted in the presence of pyrexia syndrome (ie, chills, rigors, night sweats, or influenza-like symptoms without temperature ≥ 38°C) at investigator discretion. Treatment with dab + tram was restarted at the same dose level once pts were symptom free for ≥ 24 hours. The primary endpoint is the composite rate of grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent discontinuation due to pyrexia vs a historical control from COMBI-AD (20%; 95% CI, 16.3%-24.1%). Secondary endpoints include relapse-free survival (RFS) and safety. Results: A total of 552 pts were enrolled. At the data cutoff (5 Oct 2020), all pts had completed 12 mo of treatment; median duration of follow-up was 18.4 mo. COMBI-APlus met its primary endpoint of significant improvement in composite rate of pyrexia. The composite rate was 8.0% (95% CI, 5.9%-10.6%), with rates of 3.8% for grade 3/4 pyrexia, 4.3% for hospitalization due to pyrexia, and 2.4% for discontinuation due to pyrexia. The estimated 12-mo RFS rate was 91.8% (95% CI, 89.0%-93.9%). The most common AEs (≥ 20%) were pyrexia (67.8%), headache (31.7%), blood creatine phosphokinase increase (27.9%), diarrhoea (27.0%), chills (26.4%), fatigue (25.7%), asthenia (23.6%), nausea (23.4%), rash (21.4%), and arthralgia (21.0%). AEs of any type led to permanent dab + tram discontinuation in 14.7% of pts. Conclusions: This primary analysis suggests the new adapted pyrexia management algorithm is effective in reducing grade 3/4 pyrexia, pyrexia-related hospitalization, and treatment discontinuation in pts receiving adjuvant dab + tram. The early efficacy appears consistent with that observed in COMBI-AD. The growing experience of oncologists in managing pyrexia with this simple algorithm may reduce the need for hospitalization or visits to a healthcare provider, which is highly desirable during the current COVID-19 pandemic. Thus, more pts can remain on treatment and derive benefit.Citation
Atkinson V, Robert C, Grob J-J, Gogas H, Dutriaux C, Demidov LV, et al. Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event (AE) management algorithm in patients (pts) treated with adjuvant dabrafenib + trametinib (dab + tram): Primary results of COMBI-APlus. Vol. 39, Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 9525–9525.Journal
Journal of Clinical OncologyDOI
10.1200/JCO.2021.39.15_suppl.9525Additional Links
https://dx.doi.org/10.1200/JCO.2021.39.15_suppl.9525Type
Meetings and ProceedingsLanguage
enae974a485f413a2113503eed53cd6c53
10.1200/JCO.2021.39.15_suppl.9525