The use of (palliative) chemotherapy in children with advance cancer – benefits and burdens

Paediatric Palliative Care Conference,

Dublin 25/11/17

Dr Cormac Owens

Consultant Paediatric Oncologist

Objectives and disclosures

• Disclosures are not financial

• No scientific data (not an interpretation of palliative care data)

• This represents my perspective on the journey families undertake in the setting of advanced cancer

• Stimulate questions by presenting my view of the landscape

Introduction

Julia is a 4 year old girl from Athlone. She lives at home with her Mum and Dad and 1 year old brother Adam. Mum is 32 weeks pregnant. Dad is a soldier based in the barracks and Mum does accounts for her Dad who is a farmer. They are very happy.

Introduction

Julia is a 4 year old girl from Athlone. She lives at home with her Mum and Dad and 1 year old brother Adam. Mum is 32 weeks pregnant. Dad is a soldier based in the barracks and Mum does accounts for her Dad who is a farmer. They are very happy.

Julia has had a fever for a few days. She is irritable and parents notice she is developing a lot of bruising. The GP diagnoses her with a viral illness. 2 days later she is worse and her parents are very worried. She is pale, lethargic and refuses to weight bear. Her tummy is distended and sore. She is referred to her local ED in Ballinasloe.

Introduction

Julia is a 4 year old girl from Athlone. She lives at home with her Mum and Dad and 1 year old brother Adam. Mum is 32 weeks pregnant. Dad is a soldier based in the barracks and Mum does accounts for her Dad who is a farmer. They are very happy.

Julia has had a fever for a few days. She is irritable and parents notice she is developing a lot of bruising. The GP diagnoses her with a viral illness. 2 days later she is worse and her parents are very worried. She is pale, lethargic and refuses to weight bear. Her tummy is distended and sore. She is referred to her local ED in Ballinasloe.

In hospital the junior doctor notes that she is extremely pale, has bruising around her eyes, a palpable, hard abdominal mass and is very distressed by hip pain.

Introduction

Julia is a 4 year old girl from Athlone. She lives at home with her Mum and Dad and 1 year old brother Adam. Mum is 32 weeks pregnant. Dad is a soldier based in the barracks and Mum does accounts for her Dad who is a farmer. They are very happy.

Julia has had a fever for a few days. She is irritable and parents notice she is developing a lot of bruising. The GP diagnoses her with a viral illness. 2 days later she is worse and her parents are very worried. She is pale, lethargic and refuses to weight bear. Her tummy is distended and sore. She is referred to her local ED in Ballinasloe.

In hospital the junior doctor notes that she is extremely pale, has bruising around her eyes, a palpable, hard abdominal mass and is very distressed by hip pain.

Julia is given pain relief, IV fluids and has bloods taken. She also has a urine test and an ultrasound.

Introduction

Julia is a 4 year old girl from Athlone. She lives at home with her Mum and Dad and 1 year old brother Adam. Mum is 32 weeks pregnant. Dad is a soldier based in the barracks and Mum does accounts for her Dad who is a farmer. They are very happy.

Julia has had a fever for a few days. She is irritable and parents notice she is developing a lot of bruising. The GP diagnoses her with a viral illness. 2 days later she is worse and her parents are very worried. She is pale, lethargic and refuses to weight bear. Her tummy is distended and sore. She is referred to her local ED in Ballinasloe.

In hospital the junior doctor notes that she is extremely pale, has bruising around her eyes, a palpable, hard abdominal mass and is very distressed by hip pain.

Julia is given pain relief, IV fluids and has bloods taken. She also has a urine test and an ultrasound.

2 hours after arriving in hospital, 5 days after being at a friend’s birthday party, a paediatrician tells Julia’s parents that she has life-threatening metastatic cancer called neuroblastoma and she needs to be transferred to Crumlin for treatment.

Advances in NBL treatment

SIOPEN HR NBL 1.7 Trial

The landscape

Number of children diagnosed with cancer in Ireland 2007-2016

Cancer incidence in Ireland

Number of deaths in children due to cancer (Ireland)with cancer in Ireland in 2016

Paediatric : Adult oncology

“Not just small adults, they are a different species”

• Different responses to chemotherapy• Different tolerance to treatment• Paediatric oncologist treats 40 new children/year• Medical oncologist treats hundreds of new adults/year

(500-800?)• Paediatric patient has a guardian who must make decisions• Adult patient generally makes decisions themselves

Parent of a child with cancer

• Guilt• Distress• Anger• Fear• Anxiety• Sadness

Parent of a child with cancer

• Guilt• Distress• Anger• Fear• Anxiety• Sadness

• Strength• Courage• Wisdom• Fight• Adaptability• Love

• Baby• Toddler• Child• Pre-teen• Teenager

“The patient”

• Faith?• Cultural background?• Parent?• Isolated?

Oncologist

• Physician• Paediatrician• Wisdom• Compassion• Communicator• Skill• Experience

Need for new therapies

• Treat relapse• Prevent relapse• Decrease toxicity

Modern hallmarks

Hanahan and Weinberg, Cell 2011

New targets

Checkpoint inhibition

Checkpoint inhibition

Targeted therapies in neuroblastoma

Cole K A , and Maris J M Clin Cancer Res 2012

BRAF

BRAF

McCarthur et al Lancet Onc 2014

Completed ITCC trials

Chemotherapy combi:

- Temozolomide (RubieJCO 2006)

- Irinotecan (Vassal EJC 2008)

- Gemcitabine-oxaliplatin(Geoerger EJC 2011)

- Topotecan-temozolomide (Di Giannatale EJC 2014)

Broad phase I trials

- Aplidin (Geoerger EJC 2011)

- LDE225 (SHH) (Kieran NeuroOncology 2017)

- Ridaforolimus (mTOR) (Pearson Oncotarget 2016)

- Dalotuzumab (IGF-1) (Frappaz Eur J Cancer 2016) and Rida+Dalo

- Ribociclib (CDK4/6) (Geoerger CCR 2017)

- AT9283 (Aurora A&B) (Moreno CCR 2015)

- Nab-paclitaxel (Moreno ASCO 2015)

- Lenvatinib (VEGFR)(ph,II ongoing)

- Regorafenib (multiTKI) (Geoerger ASCO 2016)

- Afatinib (EGFR)(Geoerger ESMO 2017)

- Atezolizumab (PD-L1)(in follow up)

Ongoing ITCC trials

Open NBL directed CAR T Cell Trials

Tandem ASCT Improves EFS

3-yr EFS 61.4±3.7%

Event-Free Survival From Randomization

3-yr EFS 48.4±3.8%

P = 0.0081

Single ASCT n=179---- Tandem ASCT n=176

3-yr OS 74.0±3.4%

3-yr OS 69.1±3.5%

P = 0.1850

Overall Survival From Randomization

Single ASCT n=179---- Tandem ASCT n=176

ANBL0532 Julie Park, ANR, ASCO 2016

Julia’s story

At the end of treatment, Julia’s scans show that she has new skeletal metastases. Despite this she is very well.

2 years after finishing treatment Julia presents with fevers, pallor and bone pain. Scans reveal that she has disseminated neuroblastoma.

4 years after finishing treatment Julia fractures her wrist. Imaging suggest this is a pathological fracture

Julia’s story

Julia and her parents meet her oncologist. They talk about the options and the chances of curing Julia…..

Treatment options

• Standard IV chemotherapy• Oral chemotherapy• High-dose chemotherapy (bone marrow transplant)• Surgery• Radiation• Pathway inhibitors• Immunotherapy

Treatment aims

Aims of treatment in poor prognostic situations (primary, refractory or relapsed disease):

• Induce disease response• Shrinkage• Slow down• Prevent further spread• Cure

• Treat the parents?• Altruism

Palliative care

The WHO defines palliative care (PC) as “an approach that improves the quality-of-life (QOL) of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of an early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual.”

Personalised medicine

Foundation medicine

Background

Hope?!

DFCI approach

Challenges (for me)

• When should we refer to palliative and home care teams?(refer not just mention)

Challenges

• Who is making the decision?• Parents• Child patient• Teen patient• Physician

Challenges

• Why is the decision being made? (hope?)

Challenges

• What are the goals of the decision(s)?

Challenges

• When should we refer to palliative and home care teams?

• Who is making the decision?• Parents• Child patient• Teen patient• Physician

• Why is the decision being made? (hope?)

• What are the goals of the decision(s)?

Challenges

• When should we refer to palliative and home care teams?

• Who is making the decision?• Parents• Child patient• Teen patient• Physician

• Why is the decision being made? (hope?)

• What are the goals of the decision(s)?

Acknowledgement

• Anything we get right is due to the whole team in Crumlin

• Anything we get wrong is probably because of me

Questions?