Retrospective Case Series Analysis of RAF Family Alterations in Pancreatic Cancer: Real-World Outcomes From Targeted and Standard Therapies
In: JCO Precision Oncology, Jg. 5 (2021-11-01), Heft 5
Online
academicJournal
- 1325 - 1338
PurposeIn pancreatic cancer (PC), the RAF family alterations define a rare subset of patients that may predict response to inhibition of the BRAF/MEK/ERK signaling pathway. A comprehensive understanding of the molecular and clinical characteristics of RAF-mutated PC may support future development of RAF-directed strategies.MethodsClinical outcomes were assessed across a multi-institutional case series of 81 patients with RAF family-mutated PC. Mutational subgroups were defined on the basis of RAF alteration hotspots and therapeutic implications.ResultsThe frequency of RAF alterations in PC was 2.2% (84 of 3,781) within a prevalence cohort derived from large molecular databases where BRAF V600E (Exon 15), BRAF ΔNVTAP (Exon 11), and SND1-BRAF fusions were the most common variants. In our retrospective case series, we identified 17 of 81 (21.0%) molecular profiles with a BRAF V600/Exon 15 mutation without any confounding drivers, 25 of 81 (30.9%) with BRAF or RAF1 fusions, and 18 of 81 (22.2%) with Exon 11 mutations. The remaining 21 of 81 (25.9%) profiles had atypical RAF variants and/or multiple oncogenic drivers. Clinical benefit from BRAF/MEK/ERK inhibitors was observed in 3 of 3 subjects within the V600 subgroup (two partial responses), 4 of 6 with fusions (two partial responses), 2 of 6 with Exon 11 mutations (one partial response), and 0 of 3 with confounding drivers. Outcomes analyses also suggested a trend favoring fluorouracil-based regimens over gemcitabine/nab-paclitaxel within the fusion subgroup (P = .027).ConclusionProspective evaluation of RAF-directed therapies is warranted in RAF-mutated PC; however, differential responses to targeted agents or standard regimens for each mutational subgroup should be a consideration when designing clinical trials.
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Retrospective Case Series Analysis of RAF Family Alterations in Pancreatic Cancer: Real-World Outcomes From Targeted and Standard Therapies
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Autor/in / Beteiligte Person: | Hendifar, Andrew ; Blais, Edik M ; Wolpin, Brian ; Subbiah, Vivek ; Collisson, Eric ; Singh, Isha ; Cannon, Timothy ; Shaw, Kenna ; Petricoin, Emanuel F ; Klempner, Samuel ; Lyons, Emily ; Wang-Gillam, Andrea ; Pishvaian, Michael J ; O'Reilly, Eileen M |
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Zeitschrift: | JCO Precision Oncology, Jg. 5 (2021-11-01), Heft 5 |
Veröffentlichung: | eScholarship, University of California, 2021 |
Medientyp: | academicJournal |
Umfang: | 1325 - 1338 |
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