Photodynamic therapy for high-grade squamous intraepithelial lesions: A randomized controlled trial.

BACKGROUND

Ablative/excisional surgery is the recommended therapy for cervical high-grade squamous intraepithelial lesions (HSILs) but is associated with cervical damage and elevated risk of complications upon subsequent pregnancies.

METHODS

This multicenter, randomized, controlled trial compared APL-1702 (2-g ointment containing 5% hexaminolevulinate; photoactivated at 125 J/cm2) versus placebo in adult women with cervical HSILs (randomization ratio: 2:1). Upon completion of 6-month treatment, patients in the APL-1702 group entered into a 6-month extension phase with observation only. The primary efficacy endpoint was treatment response, as defined by normal histology or low-grade squamous intraepithelial lesion (LSIL) histology plus human papillomavirus (HPV) clearance, at 6 months in a modified intent-to-treat (mITT) population.

FINDINGS: A total of 402 women were enrolled. The 6-month response rate was 41.1% (104/253) in the APL-1702 group versus 21.7% (28/129) in the placebo group (p < 0.001). The HPV16/18 clearance rates were 31.4% (49/156) and 15.4% (12/78) in the APL-1702 and placebo groups, respectively (p = 0.011). The rates of treatment-emergent adverse events were 56.8% (151/266) and 56.0% (75/134) in the APL-1702 and placebo groups, respectively. At the end of the 6-month extension period, 54.9% (56/102) of the patients who responded at the end of the 6-month treatment period maintained a response.

CONCLUSIONS

APL-1702 significantly increased the 6-month response rate in patients with cervical HSILs versus placebo control, with a favorable safety profile.

FUNDING: This trial was sponsored by Asieris Pharmaceuticals (Shanghai, China).