Correlates of fever in patients (pts) receiving combined dabrafenib (GSK2118436) plus trametinib (GSK1120212) for V600 BRAF-mutant metastatic melanoma (MM)

Clara Inkyung Lee, Alexander M. Menzies, Lauren Haydu, Arthur Clements, Richard Kefford, Georgina V. Long

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Background: Dabrafenib is an effective targeted treatment of oncogenic BRAF-mutant MM. 20-30% of pts experienced drug-related fever in phase I and II trials of dabrafenib, but not trametinib. The combination of dabrafenib and trametinib reduces skin AEs seen with either drug alone, but dabrafenib-related fever persists as a common AE. We investigated correlates of fever in pts from a single institution enrolled in the BRF113220 phase I/II study of combined dabrafenib and trametinib.Methods: Demographics, BRAF genotype, extent and burden of disease, RECIST response, PFS and OS were collected on all pts enrolled into BRF113220 at Westmead Hospital between Nov 2010 and Nov 2011. Data were collected, including the number and severity of febrile episodes, associated symptoms, haematologic and biochemical alterations, the treatment and prophylaxis of fever, and the efficacy of these measures. Results: 23 pts were enrolled. 9 pts (39%) developed fever defined as ≥38.5°C, 5 had associated rash and 6 had rigors. Fever was not associated with pt age, sex, BRAF genotype (V600E vs V600K), M-stage, sites of distant metastases, baseline LDH and baseline tumor volume (RECIST target lesions). Fever did not predict RECIST response, PFS or OS. Fever recurred in 6 pts, and was repetitive (>2 episodes) in 2 (6 and 7 episodes). Neither dose reduction of either drug, nor anti-pyretic therapy (acetaminophen, NSAIDs) were effective in fever prophylaxis, but corticosteroids were effective in all cases. 8 of 9 pts had biochemical assessment at first fever, and all had a rise in AST (median 100%), ALT (79%), ALP (40%) and LDH (40%) compared to those without fever (p<0.05). At time of first fever, there was no significant change in neutrophil or lymphocyte counts, GGT or CRP, yet lymphopaenia had developed in the 4 pts subsequently requiring corticosteroid prophylaxis. Conclusions: Fever is not predictive of response or clinical outcome, and there are no clinical characteristics which predict fever. Febrile episodes are associated with transient elevation of ALT, ALP, LDH and especially AST. Corticosteroids are the only effective fever prophylaxis.
Original languageEnglish
Pages (from-to)e19011-e19011
Number of pages1
JournalJournal of Clinical Oncology
Volume30
Issue numberSupplement 15
Publication statusPublished - 20 May 2012
Externally publishedYes
Event48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) - Chicago, United States
Duration: 1 Jun 20126 Jun 2012

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