Patrick Y. Wen, MD, is is the director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute; as well as a professor of neurology at Harvard Medical School

Patrick Y. Wen, MD, and Karisa C. Schreck, MD, PhD, discuss the safety profile and management of toxicities associated with BRAF inhibitors in central nervous system tumors.

Safety Considerations for BRAF Inhibition in CNS Malignancies

Videos

Patrick Y. Wen, MD, and Karisa C. Schreck, MD, PhD, discuss the novel BRAF inhibitor plixorafenib and its ongoing evaluation in central nervous system malignancies.

Detailing the Exploration of Plixorafenib in CNS Malignancies

Patrick Y. Wen, MD, and Karisa C. Schreck, MD, PhD, discuss the use of BRAF inhibitors in the treatment of patients with central nervous system malignanices.

The Role of BRAF Inhibition in CNS Malignancies 

Patrick Y. Wen, MD, and Karisa C. Schreck, MD, PhD, discuss current treatment approaches in central nervous system malignancies.

Current Treatment Standards in Primary CNS Malignancies

In today’s episode, supported by Chimerix, we spoke with Patrick Y. Wen, MD, about the FDA approval of dordaviprone (Modeyso) for the treatment of adult and pediatric patients at least 1 year of age with 

diffuse midline glioma who have progressive disease following prior therapy. Dr Wen is the director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute; as well as a professor of neurology at Harvard Medical School in Boston, Massachusetts.

In our conversation, Dr Wen discussed the significance of this accelerated approval across patient age groups, key efficacy and safety data that supported this approval, and the importance of biomarker testing in patients with glioma. He also highlighted potential next steps for expanding the investigation of dordaviprone in patients with glioma and emphasized the ways that multidisciplinary collaboration can provide patients with personalized, optimized care. 

That’s all we have for today! Thank you for listening to this episode of 

 supported by Chimerix. Check back throughout the week for exclusive interviews with leading experts in the oncology field.

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Podcasts

Dr Wen discussed the significance of the FDA approval of dordaviprone for patients at least 1 year of age with H3K27M-mutated diffuse midline glioma.

FDA Approval Insights: Dordaviprone in H3K27M-Mutated Diffuse Midline Glioma: With Patrick Y. Wen, MD

The Evaluation of Vorasidenib in IDH1- and IDH2-Mutated Low-Grade Glioma

Dr Wen on the Evaluation of Vorasidenib in IDH1- and IDH2-Mutated Low-Grade Glioma

Patrick Y. Wen, MD, director, Center for Neuro-Oncology, institute physician, Dana-Farber Cancer Institute, professor, neurology, Harvard Medical School, discusses the evaluation of vorasidenib in 

-mutated low-grade glioma, as evaluated in the phase 3 INDIGO trial (NCT04164901).

The INDIGO study is a multicenter, randomized, double-blind, placebo-controlled trial which sought toevaluate and compare the efficacy of vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, with placebo in patients with residual or recurrent grade 2 glioma with an 

 mutation. These patients will have undergone surgery as their only previous treatment. 

The objective of the INDIGO trial is to assess whether this drug could effectively stabilize tumors, thereby postponing the need for radiation and chemotherapy, particularly in the context of a younger patient demographic, Wen begins. Although conventional treatments show efficacy in this population, they often lead to neurocognitive issues after a decade or more, he states.

The primary end point of the trial focused on progression-free survival (PFS), and the trial was halted during the second interim analysis due to observed efficacy, demonstrating a significant extension in PFS, Wen continues. Notably, the secondary end point of time to next tumor treatment also revealed noteworthy efficacy in delaying the need for additional interventions, aligning with this key study objective, he emphasizes.

The trial evaluated a total of 331 patients, and those who received treatment with placebo exhibited an 11.1-month median PFS, whereas the vorasidenib group demonstrated a median PFS of 27.7 months. The hazard ratio was 0.39 (95% CI, 0.27-0.56; 

 < .001), Wen states. In terms of time to next tumor intervention, the median duration for the placebo group was 17.8 months, whereas for vorasidenib, the median time has not been reached. The hazard ratio was 0.26 (95% CI, 0.15-0.43; 

Patrick Y. Wen, MD, discusses the evaluation of vorasidenib in IDH1- and IDH2-mutated low-grade glioma, as evaluated in the phase 3 INDIGO trial.

The Evaluation of Tovorafenib in Young Patients with Low-Grade Glioma

Dr Wen on the Evaluation of Tovorafenib in Young Patients with Low-Grade Glioma

Patrick Y. Wen, MD, director, Center for Neuro-Oncology, institute physician, Dana-Farber Cancer Institute, professor, neurology, Harvard Medical School, discusses the efficacy of the pan-RAF inhibitor tovorafenib (DAY101) in children and young adults with low-grade glioma and highlights the importance of continual clinical research in this disease.

The phase 2 FIREFLY-1 trial (NCT04775485) enrolled patients aged 6 months to 25 years with 

-altered tumors who exhibited radiographic progression on at least 1 prior systemic therapy. Arm 1 (n = 77) included pediatric patients with low-grade glioma expressing a confirmed activating 

 V600 mutation. Arm 2 (n = 60) included pediatric patients with low-grade glioma harboring a known activating 

 V600 mutations. Arm 3 continues to enroll patients with locally advanced or metastatic solid tumors who harbor an activating 

 fusion, and whose disease relapsed, progressed, or proved unresponsive onavailable therapies.

 and more recently, the 2023 SNO Pediatric Neuro-Oncology Research Conference, investigators shared efficacy and safety findings from the 3-arm study. The overall response rate (ORR) with tovorafenib was 67%, with a clinical benefit rate (CBR) of 93% per RANO high-grade glioma criteria. The ORR according to the RANO low-grade glioma criteria was 53%, and the CBR was 61%.

Wen states that these data are promising, as there is a persistent unmet need for effective treatments in low-grade gliomas with 

 fusions. First-generation BRAF inhibitors have proved ineffective and sometimes even exacerbated tumor growth acceleration in certain patients, he explains. However, the emergence of type 2 BRAF inhibitors, like tovorafenib, has proven to be successful, Wen emphasizes.

Response rates for patients with low-grade glioma continue to be high and durable, Wen states. This is important because gliomas are often associated with poor prognosis, despite being considered a relatively rare tumor type, he adds. Moreover, lower-grade gliomas predominantly affect young adults, underscoring the need for effective options, Wen imparts.

Patrick Y. Wen, MD, discusses the efficacy of the pan-RAF inhibitor tovorafenib in children and young adults with low-grade glioma and highlights the importance of continual clinical research in this disease.


Patrick Y. Wen, MD