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.
Resources from the same session
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract
5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Presenter: Jonas Jarczyk
Session: Poster Display session 3
Resources:
Abstract
5204 - A differential bladder microbiota composition is associated with tumor grade in bladder cancer.
Presenter: Monica Parra-Grande
Session: Poster Display session 3
Resources:
Abstract
4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)
Presenter: Victor Sacristan Santos
Session: Poster Display session 3
Resources:
Abstract
5370 - Evaluation of different diagnostic methods for identification of FGFR alteration in advanced urothelial carcinomas: Proficiency Results based on multiple RNA extraction kits and mutation detection methods
Presenter: Veronika Weyerer
Session: Poster Display session 3
Resources:
Abstract
2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers
Presenter: Esmail Al-ezzi
Session: Poster Display session 3
Resources:
Abstract
2203 - TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy
Session: Poster Display session 3
Resources:
Abstract
4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B
Presenter: Cristina Suárez
Session: Poster Display session 3
Resources:
Abstract
2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A
Presenter: James Larkin
Session: Poster Display session 3
Resources:
Abstract
2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract