Management choices in breast cancer: interactive case studies

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Management choices in breast cancer interactive
case studies

• Andrew Wardley
• Christie Hospital and South Manchester University
  Hospital, Manchester, UK

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Clinical case study 1 19761986

• A 46-year-old woman diagnosed with right breast
  cancer
• mastectomy and axillary clearance
• tumour T2/N0
• no adjuvant treatment
• ?10 years later right thigh pain
• lytic disease in both femora and right iliac
  bone biopsy ? adenocarcinoma
• ER-positive/PR-negative
• Radiotherapy tamoxifen

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Disease recurrence 2002

• Aged 72 she had
• dyspnoea, cough and right chest wall discomfort
• She was referred to medical oncology with
• right pleural effusion
• anorexia
• substantial hepatomegaly
• CT scan revealed
• pleural thickening
• lung metastasis 5.0 x 2.0cm
• multiple liver metastases (largest 2.8 x 2.0cm)
• A bone scan showed degenerative disease only

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Metastases confirmed by CT scan
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Elevated liver enzymesand hypercalcaemia
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Treatment course 2002

• Tamoxifen discontinued
• Commenced letrozole
• plus ibandronate
• After 12 weeks of letrozole
• effusion worse
• liver enzymes worse
• alkaline phosphatase 247 ? 379
• GGT 2429 ? 3505

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Xeloda monotherapy highly active front-line
therapy for MBC
1Talbot D et al. Br J Cancer 200286136772
2OShaughnessy J et al. Ann Oncol 200112124754
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Xeloda monotherapy in patients ³65
yearseffective and well tolerated in first-line
MBC

• Median age 73 years (6589)
• No grade 3 / 4 myelosuppression
• Dose modification 9 patients (30) from 1 250
  1 patient (2.3) from 1 000

Procopio G et al. Eur J Cancer 20031(Suppl.
5)S138 (Abstract 451)
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July 2002 first-line Xeloda monotherapy

• In July 2002 she began treatment with Xeloda 1
  250mg/m2 twice daily, days 114, q21d
• After 4 cycles
• felt better and appetite improved
• liver enzymes improving
• reduction in size of liver metastasis
• After 15 cycles
• weight gain of 4kg
• PS 0
• liver enzymes normal
• liver edge just palpable

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Post-Xeloda CT scans
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Continued management with Xeloda

• April 2004 after 25 cycles of full-dose Xeloda
  she developed grade 2 hand-foot syndrome
• How would you further manage this patient?

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Xeloda continued at reduced dose

• Xeloda dose was reduced to 1 000mg/m2 twice
  daily, days 114, q21d
• Continues on Xeloda and is free from progression
  (PS 0)

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Case summary

• After failure of two hormonal therapies this
  patient with liver dysfunction was treated
  withXeloda monotherapy
• rapid response
• rapid symptom relief
• She received full-dose Xeloda for 25 cycles
• well tolerated
• she continues on reduced-dose Xeloda

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Clinical case study 2

• A 42-year-old woman was diagnosed with right
  breast cancer and underwent a wide local excision
  with axillary clearance
• Tumour 2.2cm, grade 3
• ER / PR strongly positive
• HER2-negative by IHC
• 1 / 16 nodes positive
• Adjuvant chemotherapy 4 x epirubicin 4 x CMF
  followed by tamoxifen

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Recurrence ?2 years post adjuvant

• Bone lesions in left sacrum, fifth lumbar
  vertebra, right second rib
• Pelvic CT scan destructive lesion in left sacrum
  with extension into paraspinous adipose tissue
• Chest and abdominal CT scans negative
• CA-27.29 was elevated (160U/L)
• She was treated with anastrozole, radiotherapy to
  the left sacrum and monthly pamidronate
• significant pain relief
• CA-27.29 reduced to 40U/L

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Clinical course hormonal therapy

• Disease progression after 1 year of anastrozole
• CA-27.29 increased to 187U/L
• worsening pain in left sacral region and left leg
• CT scans progressive bone disease and
  paraspinous disease not evident no visceral
  involvement
• She received fulvestrant for 4 months
• CA-27.29 continued to rise 320U/L
• worsening bone pain
• paraspinous mass in radiation field
• no visceral metastases

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Chemotherapy is an appropriate choice

• Young, fit patient
• Rapidly progressing disease
• Relapse 2 years of adjuvant anthracyclines (poor
  prognosis)
• Two lines of hormonal therapy in the metastatic
  setting have failed

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XT achieves superior outcomesin MBC TTP, ORR
Estimated probability
1.0 0.8 0.6 0.4 0.2 0.0
ORR
XT (n255) 42 Taxotere (n256) 30
p0.006
Log-rank p0.0001
4.2
6.1
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Months
OShaughnessy J et al. J Clin Oncol
200220281223
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Estimated probability
1.0 0.8 0.6 0.4 0.2 0.0
XT Taxotere
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Months
1OShaughnessy J et al. J Clin Oncol
200220281223
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Clinical outcome rapid, effective disease
control with XT

• The patient received approved dose
• Xeloda 1 250mg/m2, twice daily, days 114
• Taxotere 75mg/m2, day 1, q21d
• Following two cycles of XT she achieved a PR
• bony pain had resolved
• CA-27.29 decreased to 46U/L

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Patient management

• Grade 2 stomatitis developed during cycle 3
• treatment interrupted until resolution
• Cycle 4 with full-dose XT was uncomplicated
• Grade 2 stomatitis recurred during cycle 5

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Continuing management

• Doses of both agents were reduced by ?25
• Xeloda 950mg/m2 twice daily, days 114
• Taxotere 55mg/m2 day 1, q21d

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Fewer grade 3 / 4 adverse events afterTaxotere
and Xeloda doses are reduced
Cycles ()
20 16 12 8 4 0
Both full doses (670 cycles)
Both reduced (405 cycles)
Diarrhoea Stomatitis Hand-foot Neutropenic syn
drome fever
F. Hoffmann-La Roche, data on file
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XT dose reduction does not compromise efficacy
overall survival
Estimated probability
1.0 0.8 0.6 0.4 0.2 0.0
Cycle 2 dose Both full (X 1 250mg/m2 T
75mg/m2) Both reduced (X 1 000mg/m2 T 60mg/m2)
15.0
14.6
0 5 10 15 20 25 30 35 40 45 50
Months
F. Hoffmann-La Roche, data on file
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Reassessment after six cycles of XT

• Asymptomatic
• CT scan sclerotic lesion in sacral region
• Bone scan reduced uptake
• CA-27.29 level ?40U/L

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Treatment course after six cycles of XT

• She continued on single-agent Xeloda 1 000mg/m2
  twice daily, day 114, q21d
• After 2 months CA-27.29 level fell further to
  19U/L
• The patient remained stable for ?1 year

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Case summary

• After the failure of two hormonal therapiesthe
  patient was treated with XT
• rapid response
• rapid symptom relief
• Tolerable with active side-effect management
• After six cycles of XT, she continued with Xeloda
  monotherapy for a full year
• Performance status improved

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XT extending survival in MBC

• Only cytotoxic chemotherapy combination to
  improve survival over Taxotere monotherapy in
  patients with pretreated MBC
• standard of care for fitter patients
  withrapidly-progressing disease
• One-third of patients in the pivotal study were
  treatedin first line
• Dosing flexibility allows management of XT side
  effects

OShaughnessy J et al. J Clin Oncol
200220281223