Imiquimod 5% Cream Inferior to Surgical Excision in Nodular and Superficial Basal Cell Carcinoma
In a noninferiority trial (SINS) reported in The Lancet Oncology, Bath-Hextall et al compared imiquimod 5% cream vs surgical excision for nodular and superficial basal cell carcinomas. Imiquimod cream was found to be inferior to surgical excision, but it may have a role in treatment of low-risk disease.
Study Details
In this trial, conducted at 12 UK centers, 501 patients of any age with histologically confirmed primary nodular or superficial basal cell carcinoma at low-risk sites were randomly assigned to receive imiquimod 5% cream once daily for 6 weeks for those with superficial lesions or 12 weeks for those with nodular lesions (n = 254) or surgical excision with a 4-mm margin (n = 247). The primary outcome measure was the proportion of patients with clinical success defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment in the modified intent-to-treat population. The prespecified noninferiority margin was relative risk (RR) of 0.87 for surgery vs imiquimod.
The imiquimod and surgery groups were generally balanced for age (median, 69 and 67 years), sex (59% and 61% male), lesion diameter (median 12 and 10 mm), lesion site (eg, face for 37% and 33%, trunk for 38% and 39%), immunocompromised status at baseline (5% and 3%), previous basal cell carcinoma (33% and 36%), and history of other skin cancers (7% and 6%).
At 3 years, 401 (80%) patients were included in the modified intention-to-treat population, including 213 in the imiquimod group and 188 in the surgery group. Patients excluded from the analysis consisted of: 5 imiquimod and 18 surgery patients who did not receive the study intervention, including 7 surgery patients who received the incorrect surgical procedure; 31 imiquimod and 41 surgery patients who were lost to follow-up; and 5 imiquimod patients and 2 surgery patients who had missing endpoint data.
Successful Treatment Rates
At 3 years, treatment was successful in 178 (84%) imiquimod patients vs 185 (98%) surgery patients (RR = 0.84, P < .0001), with the outcome establishing inferiority of imiquimod treatment. Treatment was successful in 85% (97/114) of imiquimod patients vs 98% (96/98) of surgery patients with superficial lesions and in 82% (81/99) vs 99% (89/90) with nodular lesions.
Cosmesis and Pain
There was no significant difference between groups for patient-rated cosmetic appearance of lesions at 6 months and 3 years. As rated by two independent dermatologists, imiquimod treatment was associated with significantly greater rates of good or excellent cosmetic appearance for all lesions (35% vs 16%, P < .0001) and head and neck lesions (60% vs 27%, P = .0003) at 6 months and for all lesions (61% vs 36%, P < .0001) and head and neck lesions (63% vs 40%, P = .007) at 3 years. Moderate to severe pain was reported by 30% of imiquimod patients vs 22% of surgery patients during treatment and by 9% vs 20% during 16-week follow-up; no pain was reported by 30% vs 31% during treatment and by 58% vs 27% during follow-up.
Adverse Events
Adverse events occurred in 94% of imiquimod patients vs 92% of surgery patients in the first 6 months and in 95% vs 91% during the trial. The most common mild or moderate adverse events were itching at lesion site (85% vs 56%), weeping at lesion site (64% vs 35%), new basal cell carcinoma (26% vs 24%), erythema/redness at lesion site (22% vs 4%), and cold or flu-like symptoms or feeling unwell (21% vs 9%).
Severe, life-threatening, or disabling adverse events consisted of cold or flu-like symptoms (3% vs 0%), inflammatory reaction to treatment (2% vs 0%), heart attack or heart failure (1% vs 2%), and pneumonia (< 1% vs 2%). Serious adverse events occurred in 39% vs 42% of patients, with no serious adverse events or on-study deaths considered treatment-related. Drug treatment for adverse events occurred in 63% and 61% of patients. Dose reduction was required in 15% of imiquimod patients, and 5% of imiquimod patients and 2% of surgery patients withdrew from the study due to adverse events. Suboptimal imiquimod dosing occurred in 6% of patients.
The investigators concluded, “Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion.”
They noted that practitioners may consider the success rate with imiquimod at 3 years to be clinically useful, since low-risk recurrences of basal cell carcinoma can be treated. They noted, “[S]ome policy makers might consider use of topical imiquimod as part of a sequential treatment approach that treats most people with low-risk lesions successfully at home and those who fail with surgery. Use of imiquimod cream for low-risk basal-cell carcinoma might be a matter of patient choice guided by convenience and acceptability of the intervention….”
Hywel C. Williams DSc, of the University of Nottingham, is the corresponding author for The Lancet Oncology article.
The study was funded by Cancer Research UK. The study authors reported no potential conflicts of interest.
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