Impact of targeted treatment in the management of Low-grade glioma - PowerPoint PPT Presentation

ESMO Preceptorship Programme Tumor Type – Location – Date Maria Vieito MD, Msc Medical Oncologist GU, Sarcoma and Neuroncology Unit Vall d'Hebron University Hospital Impact of targeted treatment in the management of Low-grade glioma

Disclosures  Roche: Travel grant to ESMO meeting. ESMO PRECEPTORSHIP PROGRAMME

26-year-old woman with refractory low- grade glioma  Initial diagnosis Pilocitic Astrocytoma in 1994(aged 3 years) – Partial resection + adjuvant XRT (41 Gy)  First relapse: 1997- Observation until 2000: – Second (complete) resection + Adjuvant carboplatin+ vincristine CT  Second relapse: 2002 – Third (complete) resection, no adjuvant treatment due to postsurgical LCR fistula  Third relapse: December 2015 – Fourth(partial) resection: the pathologist notes a change in morphology, compatible with neuroglial tumor/vs/G2 xantoastrocitoma – Multiple postsurgical complications: bleeding, thrombosis, SIADH…  Fourth relapse: June 2016 – Palliative treatment with Temozolomide + inclusion in molecular pre- screening program ESMO PRECEPTORSHIP PROGRAMME

Molecular prescreening in patients with low grade tumors: recurrent targetable mutations Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas ESMO PRECEPTORSHIP PROGRAMME • TCGA ntework New England Journal of Medicine 2015 vol: 372 (26) pp: 2481-2498

Molecular prescreening program for patients with low grade tumors: some targetable translocations Emerging Gene Fusion Drivers in Primary and Metastatic Central Nervous System Malignancies: A Review of Available Evidence for Systemic Targeted Therapies. Brastianos P, Ippen F, Hafeez U, Gan H. The oncologist. 2018 pp: theoncologist.2017-0614 ESMO PRECEPTORSHIP PROGRAMME

Molecular prescreening in patients with low grade tumors: xanthoastrocytomas vs neuroglial tumors Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Zhang J Wu G Miller C Tatevossian R Dalton J et. al. Nature genetics, 2013 vol: 45 (6) pp: 602-12 ESMO PRECEPTORSHIP PROGRAMME

Molecular prescrening results:  IDH wt, p53 wt, ATRX wt, IHQ for EGFR negative, PTEN conserved.  Mutation panel of 50 genes: negative. Translocation panel: FGFR1 E17-TACC1 E7 ESMO PRECEPTORSHIP PROGRAMME

FGFR translocations in glioma HINT: IDH wt, low grade, benign tumor FGFR-TACC gene fusions in human glioma. Lasorella A, Sanson M, Iavarone A Neuro-Oncology 2017 vol: 19 (4) pp: 475-483 Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Zhang J Wu G Miller C Tatevossian R Dalton J et. al. Nature genetics, 2013 vol: 45 (6) pp: 602-12 ESMO PRECEPTORSHIP PROGRAMME

Targeted vs standard treatment  Temozolomide: 6 cycles from July 2016 to January 2017. – Best response SD. Several episodes of thrombocitopenia.  Progression on October 2017: – Diffuse leptomeningeal infiltration + multiple subependimary nodes  Included in clinical trial with narrow-spectrum Pan-FGFR inhibitor(not from Roche):  Ten cycles from November 2017 to June 2018. – Best response PR with -83% on target lessions and clinical response. – Significant toxicity: G4 hyperphosfatemia, G2 nausea, G2 palmoplantar disestesia, G2 fatigue… ESMO PRECEPTORSHIP PROGRAMME

June 2016 January 2017 ESMO PRECEPTORSHIP PROGRAMME

Nov 2017 April 2018 ESMO PRECEPTORSHIP PROGRAMME

Conclusions:  Children are not small adults, treating relapsed childhood tumors and tumors in AYA patients requires specific knowledge (and being willing to colaborate)  While the morphological appearance of a tumor may change, this sometimes doesn ´ t reflect a change in driver mutations  Patients with “benign” tumors have many unmet needs  The existence of molecular prescreening programs offers hope for patients with low-grade gliomas ESMO PRECEPTORSHIP PROGRAMME

Update: therapeutic resistance is an issue.. July 2018 April 2018 ESMO PRECEPTORSHIP PROGRAMME

ESMO Preceptorship Programme