NCCN Guidelines for Central Nervous System Cancers Cancer v.1.2021 – Annual 10/23/2020 Guideline Page Institution Vote Panel Discussion/References and Request YES NO ABSTAIN ABSENT GLIO-1, GLIO-5 Based on a review of the data and discussion, the 0 24 0 5 External request: panel consensus did not support the addition of these specific recommendations into the Guidelines as they Submission/NX Development Corp (06/02/20): agree that this is already covered in the Guideline. For the Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma, Anaplastic Astrocytoma, Anaplastic Gliomas and Glioblastoma (GLIO-1) workflow, under surgery, we recommend inclusion of Aminolevulinic acid hydrochloride (ALA, Brand Name Gleolan™) as an adjunct for the visualization of malignant tissue and to improve the completeness of resection during fluorescence guided glioma surgery. For the Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma, Anaplastic Astrocytoma, Anaplastic Gliomas and Glioblastoma (GLIO-5) workflow, under recurrence resection, we recommend inclusion of Aminolevulinic acid hydrochloride (ALA, Brand Name Gleolan™) as an adjunct for the visualization of malignant tissue and to improve the completeness of resection during fluorescence guided glioma surgery. GLIO-2 The panel consensus supported the removal of 24 0 0 5 Internal request: “Standard RT + neoadjuvant or adjuvant PCV” for adjuvant treatment of anaplastic astrocytoma Consider removal of “Standard RT ÷ neoadjuvant or adjuvant PCV” for adjuvant treatment of anaplastic astrocytoma BRAIN-D (1 of 15, 2 of 15, 3 of 15) The panel consensus supported the inclusion of 24 0 0 5 Internal request: larotrectinib and entrectinib for tumors with NTRK gene fusion for recurrent or progressive disease Consider including larotrectinib and entrectinib for under useful in certain circumstances for low-grade NTRK gene fusion tumors. glioma, anaplastic gliomas, and glioblastoma. NCCN Guidelines for Central Nervous System Cancers Cancer v.1.2021 – Annual 10/23/2020 BRAIN-D (1 of 15) The panel consensus supported the inclusion of 24 0 0 5 Internal request: BRAF/MEK inhibitors dabrafenib/trametinib and vemurafenib/cobimetinib for tumors with BRAF Consider BRAF/MEK inhibitors dabrafenib/trametinib V600E activation mutation for recurrent or and vemurafenib/cobimetinib for tumors with BRAF progressive disease under useful in certain V600E activation mutation. circumstances for low-grade glioma, anaplastic gliomas, and glioblastoma. BRAIN-D (1 of 15) Based on a review of the data and discussion, the 24 0 0 5 External request: panel consensus supported the inclusion of selumetinib (for pilocytic astrocytoma with BRAF AstraZeneca/Medical Affairs (May 4, 2020). Add fusion or BRAF v600E activating mutation) as an selumetinib as a treatment option for recurrent or option for recurrent or progressive disease. This is a progressive disease in patients with low-grade category 2A useful in certain circumstances glioma/pilocytic and infiltrative supratentorial recommendation. astrocytoma/oligodendroglioma. See Submission for references External request: AstraZeneca/Medical Affairs (May 4, 2020). The Panel consensus was that this request is outside 0 24 0 5 Based on the recent approval of KOSELUGO™ of the scope of the Guidelines recommendations. (selumetinib) by the FDA, we respectfully request for consideration the addition of a new section on plexiform neurofibromas to be included within the NCCN Guidelines for Central Nervous System Cancers. In addition, we request selumetinib be included as a treatment option for pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN). BRAIN-D (8 of 15) Based on a review of the data and discussion, the 24 0 0 5 Internal request: panel consensus supported the inclusion of “ado-trastuzumab emtansine (TDM1)” for brain Consider “ado-trastuzumab” for brain metastases from metastases from HER2 positive breast cancer. This HER2 positive breast cancer. is a category 2A recommendation. Reference: Montemurro F, Delaloge S, Barrios CH, et al. Trastuzumab emtansine (t-dm1) in patients with her2-positive metastatic breast cancer and brain metastases: Exploratory final analysis of cohort 1 from kamilla, a single-arm phase iiib clinical trial. Ann Oncol 2020;31:1350-1358. NCCN Guidelines for Central Nervous System Cancers Cancer v.1.2021 – Annual 10/23/2020 BRAIN-D (8 of 15) Based on a review of the data and discussion, the 24 0 0 5 Internal request: panel consensus supported moving capecitabine to HER2 non-specific breast cancer, for brain Consider moving capecitabine (category 2B) from metastases. This is a category 2A recommendation. HER2 positive breast cancer to HER2 non-specific breast cancer. BRAIN-D (8 of 15) Based on a review of the data and discussion, the 0 24 0 5 External request: panel consensus was to make no change regarding the requested inclusion of nivolumab + ipilimumab for Submission/Bristol Myers Squibb (06/23/20): Consider patients with melanoma brain metastases and wait the inclusion of nivolumab + ipilimumab for patients for publication of the data. with melanoma brain metastases. See Submission for references BRAIN-D (8 of 15) Based on a review of the data and discussion, the 24 0 0 5 External request: panel consensus supported the removal of “(EGFR T790M positive)” after “osimertinib”. Submission/AstraZeneca (04/14/20): We respectfully request that the specification “(EGFR T790M positive)” See Submission for references be removed after “osimertinib” from BRAIN-D Page 8 of 15 in the NCCN Guidelines of Central Nervous System Cancers Version 1.2020. BRAIN-D (8 of 15) Based on a review of the data and discussion, the 24 0 0 5 Internal request: panel consensus supported the inclusion of capmatinib as a treatment option for NSCLC with There are now approved MET/ROS and RET inhibitors. MET exon 14 skipping mutation and brain MET is the more meaningful since its 3-4% of NSCLC metastases. This is a category 2A recommendation. and may be a resistance mechanism. Do we want to add this? It is FDA approved. Reference: Wolf J, Seto T, Han JY, et al. Capmatinib in met exon 14-mutated or met-amplified non-small- External request: cell lung cancer. N Engl J Med 2020;383:944-957. Novartis Pharmaceuticals Corporation (December 11, 2020) consider inclusion of capmatinib as a treatment option for advanced NSCLC with MET exon 14 skipping mutation and brain metastases. .