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

ESMO Preceptorship Programme

Impact of targeted treatment in the management of Low-grade glioma

Maria Vieito MD, Msc Medical Oncologist GU, Sarcoma and Neuroncology Unit Vall d'Hebron University Hospital

Tumor Type – Location – Date

ESMO PRECEPTORSHIP PROGRAMME

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

• TCGA ntework

New England Journal of Medicine 2015 vol: 372 (26) pp: 2481-2498

ESMO PRECEPTORSHIP PROGRAMME

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

 IDH wt, p53 wt, ATRX wt, IHQ for EGFR negative,

PTEN conserved.

 Mutation panel of 50 genes: negative.

Molecular prescrening results:

Translocation panel: FGFR1 E17-TACC1 E7

ESMO PRECEPTORSHIP PROGRAMME

FGFR translocations in glioma

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

HINT: IDH wt, low grade, benign tumor

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

• ffers hope for patients with low-grade gliomas

ESMO PRECEPTORSHIP PROGRAMME

Update: therapeutic resistance is an issue..

April 2018 July 2018

ESMO Preceptorship Programme