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ESMO Preceptorship Programme

An uncommon mutation in a young patient

Pietro Paolo VitielloMedical Oncology Unit - University of Campania «Luigi Vanvitelli»

Napoli - Italy

Colorectal cancer – Barcelona – 20-21 October 2017

ESMO PRECEPTORSHIP PROGRAM

Patient: Male, 34 yo

Never smoker, BMI 23.5 kg/sqm

Comorbidity: none

Familiar history: grandmother died of

colorectal cancer aged 35


Clinical presentation: June 2016

Presentation with intense abdominal pain and signs

of bowel obstruction

Ultrasonography / CT-scan: multiple metastasis

throughout all liver segments; wall thickening at the

transverse colon (splenic flexure); multiple retroperitoneal

and mediastinal lymphnodes enlarged > 1 cm

CEA: 509,3 ng/ml

Colic resection: pT3 G3 N2b (15/17)

Slow recovery after surgery due to wound infection


Clinical evaluation

Liver function test: bilirubin 0.89 mg/dl,

AST: 132 U/L, ALT: 155 U/L, albumin: 3.1

g/dl, INR: 1.09.

Heart and renal functions are normal

At the time of first oncological evaluation

pt is ECOG PS 2

Unfit for triplet


Molecular analyses

KRAS, NRAS: wild-type

HER2: negative

Microsatellite stable

BRAF: mutated L597R (c.1790T>G)


A look at the literature

No clinical data available for L597R-BRAF mutated CRC

V600E-BRAF mutation is predictive of the lack of significantbenefit from anti-EGFR therapy in 2nd line and chemorefractorypts, but inconclusive data in 1st line setting.

BRAF codon 594 or 596 mutations (and other rarer mutations) predict a better outcome due to kinase inactivation

(Pietrantonio F et al. Eur J Cancer 2015)(Rowland A et al. Br J Cancer 2015)

(Cremolini C et al. Ann Oncol 2015)(Jones JC et al. JCO 2017)


Treatment approach

1° line: FOLFIRI + cetuximab (started 1/9/16)

First evaluation (17/11/16):

– CT-scan: Stable Disease (RECIST 1.1)

– Improved liver function

– CEA: 52,9 versus baseline 509,3 ng/ml

– ECOG PS from 2 to 0!


Treatment approach1° line: FOLFIRI + cetuximab (started 01/09/16)

Second evaluation (16/01/17):

– CT-scan: Progressive Disease (new liver

lesions) – PFS: 4.5 months

– Preserved liver and renal function

– CEA: 50,8 ng/ml

2° line: FOLFOX + bevacizumab

(started 02/02/2017)


Treatment approach2° line: FOLFOX + bevacizumab (started 02/02/17)

First evaluation (03/05/17):

– CT-scan: Stable disease

– CEA: 70,5 ng/ml (vs 50,8)

– Grade 2 hypertension under control with

ramipril


Serious Adverse Event

13/06/2017: pt is admitted to ER for suddenonset of blindness, seizures and decreasedconsciuosness brain CT-scan shows «several hypodense areas in parieto-occipitalregion, bilaterally»

MRI findings: «symmetric alteration of the white substance in occipital and parietallobes, with no contrast enhancement»

Posterior Reversible EncephalopathySyndrome (P.R.E.S.)


Posterior Reversible

Encephalopathy Syndrome Vascular syndrome characterised by reversible

endothelial damage in blood vessels and white matter oedema in posterior brain lobes

High-dose chemotherapy, antiangiogenics and uncontrolled arterial hypertension are possiblecauses in cancer patients

Visual loss, decreased consciousness, epilepsyand severe hypertension are common atpresentation

Complete recovery from neurological symptoms istypical, but the rate of recurrence is high in case of new exposure to the causing agents


Posterior Reversible

Encephalopathy Syndrome


What to do next?

Therapy with FOLFOX was rechallenged, but

bevacizumab was not administered due to

safety concerns

The following evaluation (August 2017)

evidenced massive progressive disease to

retroperitoneal lymphnodes, peritoneum,

lungs, liver and adrenal glands.

Pt unfit for further lines of therapy (bedbound,

PS 3-4) died in september (OS: 14 mo)


Discussion points

Is BRAF L597R mutation V600-like?

(Most probably: Yes)

What’s the best therapeutic approach

(1° and subsequent lines) in patients with

such uncommon mutations?


Thank you for your attention!

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