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BCC – Management and Treatment Options
Dr JT Lear,
Dermatology CentreManchester Royal Infirmary &
Dermatology CentreHope Hospital, Manchester
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BASAL CELL CARCINOMA
Management and Treatment OptionsNovember 2012
Dr John LearConsultant Dermatologist,
Central Manchester Hospitals
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Results in nBCC:Lesion response & cosmesis (PP) 3- month follow-up
Rhodes et al; Arch Dermatol 2004; 140:17–23
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Complete response
MAL-PDT Surgery
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Cosmetic outcomes
MAL-PDT Surgery
nBCC: 5 year recurrence rates MAL-PDT vs. surgery
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0102030405060708090
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3mthCRR
12mthRR
24mthRR
36mthRR
48mthRR
60mthRR
MAL-PDT
Excision
nBCC: 5 year recurrence rates MAL-PDT
• MAL-PDT has now shown long term recurrence rates: - higher (14%) than surgery (4%)– at least equivalent to recurrence rates of standard
alternative treatments to surgery
• PDT offers the benefit of non invasiveness, rapid healing and better cosmetic outcome than surgery
Long term outcomes MAL-PDT:superficial basal cell carcinoma
(sBCC)
sBCC: 5 year recurrence rates MAL-PDT vs cryotherapy
97 95
9 1317 19 2219 22
19 2220
0102030405060708090
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3mthCRR
12mthRR
24mthRR
36mthRR
48mthRR
60mthRR
MAL-PDT
Cryotherapy
sBCC: 5 year recurrence rates MAL-PDT
• No new recurrences after 36 months• Long term recurrence rates similar to recurrence
rates of standard cryotherapy (22% vs 20%)• PDT offers non invasive, rapid healing and
better cosmetic outcome than cryotherapy• Should be considered as a standard therapy for
sBCC
Long term outcomes MAL-PDT: Difficult-to-treat basal cell carcinoma BCC
Why PDT for ‘difficult-to-treat’ BCC?• Surgery, may be inappropriate in a number
of situations – Large or many lesions, poor ability to heal, poor
vasculature, co-morbidities such as immunosuppression, diabetes, anticoagulant medication
– risk of keloid scarring
Study design
• Open studies in difficult-to-treat sBCC and nBCC
• 94 patients, 123 lesions in European study• 102 patients, 187 lesions in Australian study• 2 MAL-PDT treatment sessions (160 mg/g, 3
hr); cycle repeated in the absence of CR• Assessed clinical and histological response,
recurrence, cosmetic outcome, safety
Definition of ‘difficult-to-treat’
• Definition of ‘difficult-to-treat’– large BCC:
• largest diameter >15 mm on extremities; >20 mm on trunk; >15 mm on face
– BCC lesion located in H-zone • as described by Swanson (mid-face, temple or ear)
– patient at high risk of surgical complications • bleeding abnormalities, anticoagulant medication and/or
cardiac
– recurrent lesions– Lesions in severely sun-damaged skin
Long term recurrence rates
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%
3mCRR
12mRR
24mRR
36mRR
48mRR
60mRR
Europe
Australia
Horn et al; Br J Dermatol 2003; 149(6):1242–1249; Vincuillo et al; Poster, World Congress of Cancers of the Skin, 2003
Geisse et al. 2004
Imiquimod - Phase III Studies
• 724 patients enrolled
• Imiquimod 5% cream administered either 5x/week or 7x/week for 6 weeks vs vehicle
• Biopsy confirmed sBCC meeting study size requirements (between 0.5 and 2.0 cm²)
• Tumour site clinically evaluated 12 weeks’ post-treatment, excised and evaluated histologically
Geisse et al. 2004
Comparison of Clin / Histo, and Histological Clearance
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Histologicalclearance (ITT)
IMIQ 5x/week
Res
pons
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%)
Veh 5x/week IMIQ 7x/week Veh 7x/week
Treatment group
p<0.001 vs vehicle groups
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Geisse et al. 2004
Correlation between Histological Clearance and LSR
Imiquimod 5x/week
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Erythema
% C
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Erosion Scabbing/crustingTest for trend: p<0.001 p=0.026 p<0.001
Severe
Moderate
MildNone
Imiquimod 5x/week in the Treatment of sBCC:Location: Upper mid back
Screening visit Treatment initiation Treatment week 3
Treatment week 6 Week 4 post-treatment Week 12 post-treatment
Gollnick et al. Poster presented at AAD 62nd Annual Meeting, Washington DC, 7-9 Feb 2004
Evaluation of Long-term Efficacy• Multicentre, phase III, open label, long-term
follow-up study
• Imiquimod 5x per week for 6 weeks• 182 patients (120m, 62f)• Mean age 65 yrs• Fitzpatrick skin phototypes II and III (90%)• Majority of target tumours (62%) located on
trunk• Target tumours ranged in size from 0.5 cm² to
2.0 (maximum diameter)
Gollnick, presented at AAD 2004 & data on file
Long-term sBCC Study: Results to 2-yearEstimate of sustained clearance of BCC during long-term follow-up (ITT) with 5x week dosing
for 6 weeks
Month 3
Cle
ara
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rate
(%
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97.5%
Month 6 Month 12
94.9% 93.7%
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Month 24
ConclusionsImiquimod 5% cream:
• High clearance rates, comparable to conventional treatment, with a sustained effect up to one year
• Non-invasive, non-scarring treatment option
– Excellent cosmetic results
Cryotherapy• 395 patients• Overall cure rate of 97%. • Recurrences were seen in 6 out of 225 (2.7%), at median 18
months. • The patients were treated as out-patients using local anaesthesia
and all tolerated the treatment well. 2 x 30 seconds
• Cryosurgery safe, low cost and effective method of treating selected non-melanoma skin cancer
• Follow up carefully for 2 years post-operatively.
• Br J Dermatol. 1988 Aug;119(2):231-40. Holt P
5 Flourouracil
• Fluorouracil clearance rates: • 90% for superficial BCC and • 27% to 85% for SCC in situ. • Up to 100% applying fluorouracil, experienced at
least 1 adverse event. Adverse event intensity ranged from mild to severe; erythema, pruritus, and pain were common.
• Love WE. Arch Dermatol. 2009 Dec;145(12):1431-8.
Oral Agents
• See next presentation/Slides 47 to 58
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Advanced Basal Cell Carcinoma (aBCC)
• BCC is the most commonly diagnosed human cancer worldwide1
• Most BCCs are curable by surgery; however, some can progress to locally advanced (la) or metastatic (m) disease2,3
• For patients with advanced forms of BCC, no standard therapies exist2-4
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Oral Agents
• LDE in development• 33 patients with metastatic or locally advanced BCC• Median treatment 9.8 months.• NEJM 2009 Sep 17;361(12):1164-72. Von Hoff DD et al.
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STEVIE: a Single-Arm Open-Label Study to Assess the Safety of the Hedgehog Pathway
Inhibitor, Vismodegib, in Patients with Advanced Basal Cell Carcinoma: Second
Interim Analysis
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Hedgehog signalling is critical for embryonic development1
Activation of SMO or functional loss of PTCH in >90 % of BCC2-5
1. Scales SJ, de Sauvage FJ. Trends Pharmacol Sci 2009;30:303–12. 2. Teh MT, et al. Cancer Res 2005;65:8597–603. 3. Kallassy M, et al. Cancer Res 1997;57:4731–5. 4. Unden AB, et al. Cancer Res 1997;57:2336–40. 5. Reifenberger J, et al. Cancer Res 1998;58:1798–803.
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Vismodegib is a first-in-class, oral, selective Hedgehog pathway inhibitor (HPI)
1. Dirix L, Rutten A. Future Oncol 2012;8:915–28
• Vismodegib is a small-molecule, Hedgehog pathway inhibitor, that binds to SMO1
• Molecular weight 421.3 g/mol• Vismodegib is a highly potent,
selective inhibitor of SMO
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ERIVANCE BCC, the pivotal study for vismodegib• ERIVANCE BCC led to approval of vismodegib by the FDA in
January 2012 For the treatment of adults with metastatic BCC, or with locally
advanced BCC that has recurred following surgery or who are not candidates for surgery and who are not candidates for radiation therapy
Sekulic A et al. New Engl J Med 2012;366:2171–9
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STEVIE: study design and objectives
Vismodegib(150 mg orally once daily)
Treatment until progressive disease, unexpected toxicity
or patient request to discontinue
Other anti-BCC therapy(to be decided by treating physician)
Progressive disease
Patients with locally advanced, inoperable
or metastatic BCC(n = up to 800)
• STEVIE is a single-arm open-label study to assess the safety of vismodegib in patients with advanced BCC
Primary objective:• SafetySecondary objectives:• Overall response (based on Response Evaluation Criteria in Solid Tumors
[RECIST]); objective response rate, duration of response, progression-free survival (PFS) and overall survival
• Quality of Life http://clinicaltrials.gov/ct2/show/NCT01367665 Accessed September 2012
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Conclusions
• Each topical therapy has positives / negatives, great to have a choice, but non-specific action
• Topical therapy increasingly important• Specific pathway inhibition, promise orally, side
effect profile limits use