breast cancer: old challenges, new directions? · breast cancer: old challenges, new directions? ba...

11/20/2018

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Breast Cancer: old challenges, new

directions? BA Lavery

Consultant Oncologist Sobell House 16th November 2018

What’s the scale of the problem?

• Incidence:

– 55000 new cases UK 2015

• Deaths

– 11500 deaths UK 2016

Sobell Oncology Update 2018 BALavery 14/11/2018

All ages affected

14/11/2018 Sobell Oncology Update 2018 BALavery

Risk of death varies with age


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Patterns of relapse


• triple negative more likely to relapse early, late relapse unusual

• ER pos total number relapsing before 5 years = total relapsing after, with no end date (my latest relapse was around 40 years)

• Her2 pos early relapse common before Herceptin in use, now less of a pattern

Timescale - Varies with subtype

• Bone commonest first site.

Tissues

• average 2-3 years from metastatic diagnosis

Life expectancy

What’s the outlook and

has this changed?

14/11/2018

• ESME data, 2018, 16700 consecutive newly diagnosed MBC 2008-14(French study)

• 28.5% metastatic at initial presentation

• 71.5% relapsed, median interval 3.6 years

• 65% ER pos Her2 neg

• 19% Her2 pos

• 15% Triple negative

Sobell Oncology Update 2018 BALavery

Time trends in survival – ESME data


What does it

mean in practice?


No single pattern, from tiny single lesions to widespread

multi-organ invovlement

JCC

BW

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What treatment options do we have?

14/11/2018

• Hormones

• Hormones ‘plus’

• Chemo

• Biologicals

• Radiation

• Surgery

• Bone support

• BSC


How effective are

new treatments?

14/11/2018

• Everolimus

• Pertuzumab

• Kadcyla

• CDK 4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib)


Everolimus with Exemestane improves PFS by ~6/12, after recurrence or progression on a non-steroidal AI


Pertuzumab improves PFS by ~6/12 first line with Trastuzumab and Docetaxel


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Kadcyla (Trastuzumab

Emtansine) improves PFS by ~3/12, after 2

or more previous Her2 directed

therapies


Kadcyla (Trastuzumab Emtansine) improves OS by 5-6/12, compared to Lapatinib and Capecitabine


Palbociclib with Letrozole

improves PFS by 10/12 in first line

therapy for advanced disease

14/11/2018


Palbociclib (with Fulvestrant)

improves PFS by ~ 6/12, pre/post

menopausal, after previous

endocrine therapy

14/11/2018


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What’s happened to chemo schedules? And to Patient QoL?

Single drug vs combinations vs sequentials?

Weekly vs 3weekly – eg Paclitaxel

Fixed duration vs ongoing to progression

Eg Capecitabine, Eribulin

Genomic assessment


How do we keep bones healthy?

• Bisphosphonates

• Oral clodronate

• IV Zoledronate

• Denosumab sc

• For how long???

• At what cost?

• How do we monitor?

14/11/2018


Find a friendly surgeon • Palliative resections

– Avoid messy oozing/bleeding tumours

– Help with odour control

• Does treating/resecting the primary help in the presence of metastatic disease?

• Biopsies


Find a friendly

radiologist


Facet joint injection

Rebiopsy at relapse to reassess receptor status – helps with

management decisions and can assist with establishing eligibility for trials

Vertebroplasty

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• Vertebroplasty to prevent cord compression and ease pain


Do I need a friendly geneticist?

• Mutation testing at diagnosis – germ line eg for BRCA

• personalized medicine – tumour genetic assessment to look for particular ‘targets’


Radiotherapy

• Palliation

• SABR

• Re-irradiation


Rapid Arc RT for oligometastatic disease

OUH Breast Group; Macmillan Masterclass May 2016

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What are still big problems?

• CNS disease

– intraparenchymal (covered by CH earlier – stereotactic RT)

– Leptomeningeal disease

• Triple negative disease

• Mixed responses

– Different mets within single patient will not all be the same

• Development of resistance to all therapies


Will Immunotherapy

revolutionize management of

metastatic breast cancer?

14/11/2018

• IMpassion130 trial in untreated triple neg disease (chemo plus atezolizumab vs chemo plus placebo) – overall small imrpvoement in PFS (7.2 vs 5.5 months), and larger improvement in OS(21.3 vs 17.6), with 25 vs 15.5 in PDL1 positive subgroup


IMpassion130, immunotherapy benefit in some triple negative metastatic cases


Practical concerns

14/11/2018

• ‘postcode prescribing’ (eg Fulvestrant)

• National postcode prescribing (eg Trastuzumab, Lapatinib etc)

• Knowing when to stop – should I refuse to keep treating the patient who copes better ‘being on treatment’?

• Escalation/de-escalation of therapy – getting the balance right

• Monitoring responses


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Areas of likely

growth

14/11/2018

• Immunotherapy

• ‘Liquid biopsies’ for diagnosis and monitoring

• Individualisation – eg bone support dependent on assessment of bone turnover products etc.

• PROMS, remote monitoring, telemed

• CBD???


breast cancer: old challenges, new directions? · breast cancer: old challenges, new directions? ba...

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