Abstract 4074
Background
D+T has been approved for several indications, including BRAF V600–mutant unresectable or metastatic melanoma and as adjuvant therapy following resected BRAF V600–mutant stage III melanoma. Pyrexia is a common adverse event but is generally low-grade and manageable; further characterization may optimize management and reduce permanent treatment (tx) discontinuation due to pyrexia.
Methods
Trial databases were queried for reports of pyrexia in pts treated with D and/or T, including adjuvant therapy. Indications included unresectable, metastatic, or resected stage III melanoma; non-small cell lung cancer (NSCLC); colorectal cancer, and other BRAF–mutation positive solid tumors. Data for D+T was compiled from the following trials: COMBI-AD (NCT01682083), COMBI-d (NCT01584648), COMBI-v (NCT01597908), and BRF113928 (NCT01336634). Pyrexia was graded according to the Common Terminology Criteria for Adverse Events version 4.0.
Results
A total of 1991 pts were included from clinical trials (D+T, n = 1076; D, n = 586; T, n = 329). Pyrexia was observed in 904 pts: D+T, 61% (660/1076); D, 33% (196/586); T, 15% (48/329). Of pts treated with D+T, 6% (62/1076) experienced grade 3 events and 1 of 1076 pts experienced a grade 4 event. The median time to onset was 27 d (range, 1-716 d). Recurrent any-grade pyrexia occurred in 41% (442/1076) of pts; 29% had ≥ 3 episodes. Of the 442 pts with recurrent pyrexia, 377 (85%) experienced a subsequent event within 3 mo of the first pyrexia episode. No pyrexia-related deaths were reported. Outcomes were reported for 2252 of 2253 events in pts treated with D+T across trials. Pyrexia management strategies included: tx interruption (939/2253 events [42%]), dose reduction (225/2253 [10%]), and tx discontinuation (62/2253 [3%]); ≥ 98% of events were reported to be resolved following each of the aforementioned interventions.
Conclusions
Pyrexia in pts treated with D+T is typically low-grade, occurs early during tx exposure, and most pts experience ≤ 1 episode. Tx interruption was the most frequent intervention strategy used in clinical trials. Pyrexia can be effectively managed with nearly all events reported to have been resolved at the time of the analysis.
Clinical trial identification
Pooled analysis of data from the following trials: NCT01227889, NCT01153763, NCT01266967, NCT01072175, NCT00880321, NCT01336634, NCT01584648, NCT01597908, NCT01682083, NCT01245062, NCT01037127, NCT00687622.
Editorial acknowledgement
Allison Lytle, PhD, from ArticulateScience LLC, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
C. Robert: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Array; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck. D. Schadendorf: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Immunocore; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Advisory / Consultancy: 4SC; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Mologen; Advisory / Consultancy: Sanofi/Regeneron; Speaker Bureau / Expert testimony: Roche; Travel / Accommodation / Expenses: Merck; Honoraria (self): Sysmex; Honoraria (self): Grünenthal Group; Honoraria (self): Agenus; Honoraria (self): Array BioPharma; Honoraria (self): AstraZeneca; Honoraria (self): LEO Pharma; Honoraria (self): Pfizer; Honoraria (self): Philogen; Honoraria (self): Regeneron. R. Dummer: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Novartis; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Merck Sharp & Dhome; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Bristol-Myers Squibb; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Roche; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Amgen; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Takeda; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Pierre Fabre; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Sun Pharma; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Sanofi; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Catalym. K.T. Flaherty: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Oncoceutics; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Aeglea Biotherapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Loxo; Advisory / Consultancy: Roche; Advisory / Consultancy: Asana Biosciences; Advisory / Consultancy: Incyte; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Shattuck Labs; Advisory / Consultancy: Tolero Pharmaceuticals; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy, Shareholder / Stockholder / Stock options: FOGPharma; Advisory / Consultancy: Neon Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tvardi; Advisory / Consultancy: Takeda; Advisory / Consultancy: Varestem; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: Cell Medica; Advisory / Consultancy, Travel / Accommodation / Expenses: Debiopharm Group; Shareholder / Stockholder / Stock options: Clovis Oncology; Shareholder / Stockholder / Stock options: X4 Pharma; Shareholder / Stockholder / Stock options: PIC Therapeutics; Shareholder / Stockholder / Stock options: Fount Therapeutics; Shareholder / Stockholder / Stock options: Apricity Health; Shareholder / Stockholder / Stock options: Vivid Biosciences; Shareholder / Stockholder / Stock options: Checkmate Pharmaceuticals; Shareholder / Stockholder / Stock options: Strata Oncology. H.A. Tawbi: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy: Roche; Advisory / Consultancy: Array; Research grant / Funding (institution): Celgene. A.M. Menzies: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. A. D’Amelio: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis; Shareholder / Stockholder / Stock options: GlaxoSmithKline. E. de Jong: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. E. Gasal: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. G.V. Long: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Pierre Fabre.
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