2042 Background: Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children and the majority of PLGG have activation of the MAPK/ERK pathway. Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PLGG and PN, but no clinical trial has reported its efficacy. Methods: This multicenter phase II trial includes patients aged ≥ 1 month to ≤ 25 years with progressing/refractory PLGG groups or PN. The primary objective was to evaluate the overall response rate after daily oral trametinib administration for eighteen 28-day cycles. Results: As of January 31st, 2022, 60 patients with PLGG and 45 patients with PN have been enrolled. Median age is 9.5 years (range 1.8-25.4) for PLGG and 11 years (range 0.7-19.8) for PN. Median follow-up is 18 months (range 0.1-38.1). Fifty-three patients with PLGG were evaluable. The overall response includes: 1 complete response (CR) (1.9%), 7 partial response PR (13.2%), 17 minor response MR (32.1%), 23 stable disease (SD) (43.4%) and 5 progressive disease (PD) (9.4%). Twenty-eight patients with a total of 32 PN were available for volumetric analysis. Volumetric assessment demonstrated an overall response rate of 60.7% compared to 24.1% when using RECIST 1.1 and 62.5% of PN showed a decrease of more than 20% in volume. Median volume change was a decrease of 30% (range -93.5 to 14.3). A total of 59 (69.4%) patients discontinued treatment as planned after 18 cycles and 9 (10.6%) patients had to stop trametinib due to adverse events. Conclusions: Response rates observed in our study suggest that trametinib is a potentially effective targeted therapy for patients with recurrent/refractory PLGG and PN. Treatment was overall well tolerated. This trial will continue to gather data on duration of response and long-term outcome for PLGG and PN treated with trametinib. Clinical trial information: NCT03363217.
BACKGROUND: Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS: This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. The primary objective for PN was to evaluate the overall response rate based on RECIST 1.1 criteria after daily oral trametinib administration for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS: As of January 1, 2022, 45 patients with PN were enrolled in the study. Twenty-eight completed treatment and were available for analysis. For these patients, the median age was 11.4 years (range 0.7-19.8) including 16 males (57.1%). The majority did not receive prior systemic therapies (71.4%). The median volume of PN at baseline was 49.5 cm3 (range 2.6 to 469). Among the 28 patients, 25 (89.3%) completed 18 cycles as planned. One patient discontinued due to adverse reaction, one patient refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 15.9 months (range 4.6 to 16.8). Median duration of follow-up was 29.7 months (range 17.7 to 38.1). A total of 32 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 24.1%. Volumetric assessment demonstrated an overall response rate of 60.7% and 62.5% of PN showed a decrease of more than 20% in volume. Median decrease in volume was -30% (range -93.5 to 14.3). Twenty-seven patients (93.1%) had durable response without progression (lasting ≥1 year). CONCLUSION: We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib appears effective and offers durable response.
BACKGROUND Plexiform neurofibromas (PN) are observed in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. Patients received daily oral trametinib (MEK inhibitor) for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS As of May 15, 2022, 46 patients with PN were enrolled in the study and the recruitment was completed for this study arm. Thirty-four completed treatment and were available for analysis. For these patients, the median age was 10.5 years (range 0.7-19.8). The median volume of PN at baseline was 51cm3 (range 2.6 to 487.6). Among the 34 patients, 28 (82.4%) completed 18 cycles as planned. Two patients discontinued due to adverse reaction, three patients refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 16.8 months (range 2.8 to 16.8). Median duration of follow-up was 30.4 months (range 8.2 to 42). A total of 38 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 13.1%. Volumetric assessment demonstrated an overall response rate of 64.7% (22/34 patients), and 65.8% (25/38 PN) of PN showed a decrease of more than 20% in volume. Median volume change was -30% (range -93.5 to 14.3). Thirty-one patients (91.1%) had durable response without progression (lasting ≥ 1 year). After discontinuation of treatment, one patient underwent surgery and three patients resumed MEK inhibitor. CONCLUSION We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib is effective and offers durable response.
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