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.
Field | Value | Language |
dc.contributor.author | Atkinson, Victoria | en_AU |
dc.contributor.author | Robert, Caroline | en_AU |
dc.contributor.author | Grob, Jean-Jacques | en_AU |
dc.contributor.author | Gogas, Helen | en_AU |
dc.contributor.author | Dutriaux, Caroline | en_AU |
dc.contributor.author | Demidov, Lev V. | en_AU |
dc.contributor.author | Gupta, Avinash | en_AU |
dc.contributor.author | Menzies, Alexander M. | en_AU |
dc.contributor.author | Ryll, Bettina | en_AU |
dc.contributor.author | Miranda, Flora | en_AU |
dc.contributor.author | Banerjee, Hiya | en_AU |
dc.contributor.author | Lau, Mike R. | en_AU |
dc.contributor.author | Del Vecchio, Michele | en_AU |
dc.date.accessioned | 2021-07-06T23:34:31Z | |
dc.date.available | 2021-07-06T23:34:31Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/2123/25651 | |
dc.description.abstract | 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. Clinical trial information: NCT03551626. | en_AU |
dc.language.iso | en | en_AU |
dc.subject | COVID-19 | en_AU |
dc.subject | Coronavirus | en_AU |
dc.title | 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. | en_AU |
dc.type | Article | en_AU |
dc.identifier.doi | 10.1200/jco.2021.39.15_suppl.9525 |
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