Clinical Evidence

A substantial body of clinical evidence has been accumulated which provides evidence that Metvix^®:

• Effectively treats AKs, BCCs and Bowen's disease.
• Has good long-term efficacy with low recurrence rates.
• Is selective for diseased cells, sparing healthy tissue.
• Is non-invasive with excellent cosmetic results.
• Results in rapid healing after treatment.
• Has excellent patient compliance and high patient preference.
• Is well tolerated with manageable side effects.

From several multi-centre, randomised, controlled clinical trials it can be concluded that Metvix^® is as effective as commonly used treatments in the elimination of BCC lesions and more effective than cryotherapy in treating AK lesions. Metvix^® offers significantly better cosmetic outcome compared with conventional therapy in the treatment of BCC and AK.

The key studies are summarised in Tables 1-4 and major findings described below:

AK

Three-month (lesion) complete response rates for Metvix^® are consistently high at around 90% (for one treatment session, repeated in case of incomplete response).^6,11,15

Cryotherapy is usually regarded as the standard therapy in the treatment of AK. A study in over 200 patients compared Metvix^® with placebo PDT (no photosensitising agent) and cryotherapy. At 3 months, the complete lesion response rate in the Metvix^® group was significantly higher (91%), than with cryotherapy (68%; p<0.001) or placebo (30%; p<0.001).⁶

Moreover, excellent overall cosmetic outcome was achieved in significantly more Metvix^® patients than cryotherapy patients as assessed by both the treating physician (83% vs. 51%; p<0.001) and the patients themselves (76% vs. 56%; p=0.013).⁶

A study of 80 patients with AK compared Metvix^® with placebo PDT (no photosensitising agent). At 3 months, complete lesion response rate in the Metvix^® group was significantly higher (89% vs. 38%; p=0.001).¹¹

sBCC

Clearance rates with Metvix^® at 3 months range from 97% in primary sBCC to 85% in complex cases, with recurrent, large or H-zone lesions^8,18.

In a study of primary sBCC, Metvix^® was compared with cryotherapy in 118 patients. At 3 months, Metvix^® and cryotherapy were equally effective in eliminating sBCC lesions (complete lesion response rates for Metvix^® and cryotherapy of 97% and 95%, respectively). Recurrence rates were similar in the Metvix^® group and the cryotherapy group after 4 years (22% vs. 19%).¹⁹

Overall cosmetic outcome in complete responders was superior for Metvix^® compared with cryotherapy at 3 months.¹¹

nBCC

Consistent complete response rates of 73-94% at 3 months have been observed with Metvix^®. Histological evaluations have confirmed the reliability of efficacy data (78% and 73%).^1,21. Even in 'difficult to treat', and 'high risk' cases, 3-month response rates of 89% were still obtained. ^{16, 17}

Excision surgery is usually regarded as the treatment of choice for nBCC. Metvix^® was compared with standard excision surgery in a study in over 100 patients. At 3 months, Metvix^® and surgery were found to have equivalent efficacy in eliminating nBCC lesions. Complete lesion response rates  for Metvix^® and standard excision surgery were 91% and 98% respectively.¹⁰

Cosmetic outcomes in complete responders however were superior for Metvix^®. Three months after treatment, 95% of patients in the Metvix^® group rated their cosmetic outcome as excellent or good, with corresponding physician assessments of 82% for the Metvix^® compared to 33% for surgery (p=0.001).¹⁰

BD

Metvix^® proved to be statistically superior to placebo-PDT and non-inferior to the standard treatments cryotherapy and 5-FU. Complete response was achieved in 93% of the lesions treated with Metvix^® vs 21% with placebo, 86% with cryotherapy and 83% with 5-FU.¹⁴ Lesion recurrence rates at 12 months with Metvix^® were comparable to cryotherapy and 5-FU (15% for Metvix^®, vs 21% for cryotherapy and 17% for 5-FU).

Cosmetic outcomes in complete responders at 12 months were superior to those of cryotherapy (97% of patients had “good” or “excellent” cosmetic outcome with Metvix® vs 62% with cryotherapy), and similar to 5-FU.

Individual Clinical Trial Summaries

Click here for access to summaries of key clinical trials.

Table 1. Key clinical studies of Metvix^® in AK

*CR=complete response. Outcomes are PP population unless otherwise stated.

Table 2. Key clinical studies of Metvix^® in sBCC

Clinical Study	Study Design	Patient nos.	Treatments	Outcomes*
Metvix®16	Retrospective trial	131 sBCC lesions	1 x Metvix® (lesion preparation) Follow up at 24-48 months	3 month lesion CR of 91% 9% relapse at 35 months 'Excellent' cosmetic outcomes for 79% of lesions
Metvix® 'difficult to treat' BCC patients (European trial) 8	Open-label multicentre trial	94 patients (49 sBCC lesions, 52 nBCC lesions)	2x Metvix®, re-treated after 3 months as necessary (lesion preparation) Follow up 3 months after last treatment	3 month lesion CR 92% (87% nBCC) (histologically controlled): 85% (75% nBCC) 'Excellent' or 'good' cosmetic outcome for 94% of total (s+nBCC) patients at 24 months
Metvix® 'high risk' BCC patients (Australian trial) 17	Open-label multicentre trial	80 sBCC lesions (33 nBCC lesions)	2x Metvix®, re-treated after 3 months as necessary (lesion preparation) Follow up at 24 months	3 month lesion CR of 93% 24 month cumulative treatment failure rate (s+nBCC) of 24% 'Excellent' or 'good' cosmetic outcome for 84% of total (n+sBCC) patients at 24 months - total population
Metvix® v. cryotherapy (European trial)18	Randomised multicentre trial	118 patients 219 lesions (102 treated with Metvix®)	1x Metvix® v. 2x cryotherapy Patients re-treated with 2x Metvix® (7 days apart) or 2x cryotherapy as necessary after 3 months (lesion preparation)	3 month lesion CR  for Metvix® (97%) comparable to cryotherapy (95%) 'Excellent' or 'good' cosmetic outcomes for 89% of patients with Metvix® v.  50% for cryotherapy after 3 months

*CR=complete response. Outcomes are PP population unless otherwise stated.

Table 3. Key clinical studies of Metvix^® in nBCC

Clinical Study	Study Design	Patient nos.	Treatments	Outcomes*
Metvix® 16	Retrospective trial	168 nBCC lesions	1 x Metvix® (lesion preparation) Follow up at 24-48 months	3 month lesion CR of  89% 35 month recurrence rates of 7% for thin nBCC and 14% for  thick nBCC
Metvix® 'Difficult to treat' BCC patients(European trial) 8	Open-label trial	94 patients(52 nBCC lesions,  49 sBCC lesions)	2x Metvix®, re-treated after 3 months as necessary (lesion preparation) Follow-up 3 months after last treatment	3-month lesion CR of 87% (92% sBCC), (histologically controlled): 75% (85%, sBCC)
Metvix® vs.surgery (European trial) 10	Randomised multicentre open-label trial	101 patients 110 lesions (56 treated with Metvix®)	2x Metvix® (7 days apart) v.  surgical excision (lesion preparation) Follow up at 3 months	3 month lesion CR for Metvix® (91%) comparable to surgery (98%) 'Excellent' or 'good' cosmetic outcome for 82% of patients treated with Metvix® v. 33% for surgery after 3 months
Metvix® v. placebo PDT (US trial)21	Randomised placebo-controlled double-blind trial	65 patients 80 lesions (41 treated with Metvix®)	2x Metvix® (7 days apart) re-treated after 3 months as necessary v.  placebo PDT (lesion preparation) Follow up at 6 months after last treatment	6 month lesion CR (clinical and histological) Metvix® (80% and 78%, respectively) v. placebo (51 and 33%, respectively) 'Excellent' or 'good' cosmetic outcome for 93% of patients treated with Metvix®. 60% patients rated Metvix® better than  previous treatment
Metvix® v. placebo PDT. (Australian trial) 1	Randomised placebo-controlled double-blind trial	66 patients	2x Metvix® (7 days apart) re-treated after 3 months as necessary v. placebo PDT (lesion preparation) Follow up at 6 months after last treatment	6 month lesion CR (histologically controlled) for Metvix® (73%) > placebo PDT (21%) 'Excellent' or 'good' cosmetic outcome for 95% of patients treated with Metvix®
Metvix® 'High risk' BCC patients (Australian trial) 17	Open-label trial	33 nBCC lesions (80 sBCC lesions)	2x Metvix®, re-treated after 3 months where necessary (lesion preparation) Follow up at 24  months	3 month lesion CR of  82% 24 month cumulative treatment failure rate (s+nBCC) 24% 'Excellent' or 'good' cosmetic outcome in 84% total patients (s+nBCC) at 24 months

*CR=complete response. Outcomes are PP population unless otherwise stated.

Table 4. Key clinical study of Metvix^® in BD

Clinical Study	Study Design	Patient nos.	Treatments	Outcomes*
Metvix® v. cryotherapy and 5-FU (European trial)14	Randomised placebo-controlled multicentre trial (Metvix® and placebo PDT arms were double-blind)	225 patients  275 lesions (124 treated with Metvix®)	2x Metvix® (7 days apart) v. 1x cryotherapy, 5-FU or placebo PDT. Re-treated after 3 months as necessary Follow up at 12 months	3 month lesion CR for Metvix®  (93%) v. 5-FU (83%) v. cryotherapy (86%) 12 month recurrence rates of 15% for Metvix®  v. 21% for cryotherapy and 17% for 5-FU Cosmetic outcomes at 3 months classed as 'good' or 'excellent' for 94% of patients receiving PDT v. 66% for cryotherapy and 76% for 5-FU (at 12 months: 97%, 62%, and 94%, respectively)

*CR=complete response. Outcomes are PP population unless otherwise stated.

References