Molecular therapy for papillary craniopharyngioma: a multi-institutional analysis of practice patterns across the RAPID Consortium.
This multi-institutional retrospective analysis reports frequent radiographic responses to BRAF-directed therapy in BRAF V600E-mutant papillary craniopharyngioma and identifies radiation-sparing, monotherapy, and longer-course strategies as feasible options requiring further study.
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This multi-institutional retrospective analysis reports frequent radiographic responses to BRAF-directed therapy in BRAF V600E-mutant papillary craniopharyngioma and identifies radiation-sparing, monotherapy, and longer-course strategies as feasible options requiring further study.
Research significance
The reported human observational evidence supports activity of BRAF and/or BRAF–MEK inhibition in BRAF V600E-mutant papillary craniopharyngioma; it is reasonable but not proven to hypothesize that optimized targeted-therapy regimens could reduce radiation exposure and associated toxicity while preserving tumor control, particularly in younger patients.
Source abstract
PURPOSE: Targeted therapy for BRAF V600E mutant papillary craniopharyngioma (PCP) has been rapidly accepted, though given the rarity of the tumor, there is limited guidance for appropriate use. Here, we retrospectively evaluated current practice patterns for the implementation of targeted therapeutics and their outcomes in the treatment of papillary craniopharyngioma (PCP). METHODS: Practice patterns at the institutions in the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) for treatment of BRAF V600E mutated PCPs using targeted therapy were evaluated. Baseline clinical and demographic variables were retrospectively recorded. Imaging response was evaluated. Dosing, treatment course, adverse events (AEs) and other therapeutic strategies employing BRAF/MEK inhibitors were studied. Adjuvant and/or salvage therapies, including radiation and surgery were recorded. RESULTS: Most patients demonstrated at least partial response to BRAF and/or BRAF/MEK inhibition (13/19, 72.2%). No patients progressed through therapy. Grade 0-2 AEs occurred in 79% of cases, and nine (47.4%) patients eventually discontinued therapy. Radiation-sparing regimens demonstrated similar radiographic response rates and had smaller residual tumor volume after treatment completion (23.7 vs. 612.4 mm3, p = 0.040) compared to those receiving radiation. BRAF monotherapy demonstrated similar rates of response to therapy, but fewer Grade 3-4 AEs (0% vs. 28.5%) than dual therapy. Long-course therapy (> 4 cycles) resulted in radiographic response (p = 0.024) more often than a short-course (≤ 4 cycles), with similar AEs. Median follow-up duration was 19 months from surgery (range: 8-63). CONCLUSION: Critical insights into molecular therapeutic practice patterns for treatment of PCP were identified. Radiation-sparing, mono-therapeutic, and prolonged treatment duration are feasible options and warrant further study.