Noninvasive device targets precancerous cervical lesions with minimal risk

A novel device that integrates hexaminolevulinate (HAL) hydrochloride (HCl) with photodynamic therapy for the treatment of cervical histologic high-grade squamous intraepithelial lesions (HSIL) has shown good results in the global phase III APRICITY study, with lasting efficacy and an acceptable safety profile.

Called APL-1702, the device yielded a response rate of 41.1 percent at 6 months after the first treatment. This response was significantly higher than the 21.7 percent obtained with placebo (p=0.0001), reported one of the study investigators Dr Yue Wang of Henan Provincial People's Hospital in Zhengzhou, China. [Wang Y, et al, SGO 2024]

Patients who received APL-1702 also had a much higher clearance rate of HPV 16/18 compared with those who received placebo (31.4 percent vs 15.4 percent; p<0.05).

According to Wang, APL-1702 had sustained efficacy, with more than half (54.9 percent) of the patients who achieved a response at 6 months having maintained that response at the 12-month follow-up. Around 40 percent of patients who had low-grade squamous intraepithelial lesions (LSIL) and nonclearance of baseline HPV at 6 months had shown improvements by 12 months.

The overall response rate with APL-1702 at 12 months was 44.4 percent, of which 58.3 percent accounted for maintained responses and 41.7 percent for new responses. Wang also noted a trend of increasing HPV clearance rates during this period.

Safe photodynamic treatment

“APL-1702 is a small medical device made of medical-grade silicone, about the size of a tampon, with a cup-shaped emission light source at the end, for photodynamic treatment of precancerous cervix,” Wang explained.

The device contains a photosensitizer HAL ointment, which Wang noted would be effectively absorbed by precancerous or cancerous cells, where the drug is converted into a molecule used in photodynamic therapy.

“Based on the principle of photodynamic, photosensitizers are combined with light activation of specific wavelengths to produce therapeutic effects,” she said.

The device, according to Wang, offers a noninvasive alternative especially for women of reproductive age, for whom traditional excisional and ablative methods might pose perinatal complications such as preterm labour, low birth weight, and perinatal death.

Indeed, APL-1702 had a manageable safety profile, with the frequency of treatment-emergent adverse events (TEAEs) being similar with that recorded with placebo (56.8 percent and 56.0 percent, respectively). Wang pointed out that most TEAEs were mild, transient, and easily tolerated.

Treatment-related adverse events were 31.6 percent with APL-1702 and 26.1 percent with placebo. Serious adverse events (SAEs) occurred infrequently, with a rate of 1.5 percent in both treatment arms.

At 12 months, the rates of TEAEs and SAEs with APL-1702 were 23.6 percent and 1.9 percent, respectively, none of which was related to treatment.

Merits and open questions

Study discussant Dr Kristin Bixel of the Ohio State University Comprehensive Cancer Center in Columbus, Ohio, US, looked at the advantages of using APL-1702 in the treatment of HSIL and explored considerations for its broader use.

“The benefit of a therapy like this is that it’s low risk, it’s office-based, and it doesn’t need anaesthesia,” Bixel said. “It had very limited treatment adverse events that were quite manageable and doesn’t require any anatomic disruption of the cervix, which can have an impact on fertility, cervical stenosis, and pelvic pain, among others.”

On the other hand, Bixel pointed out that the cost of the device was a critical factor, considering the potential frequency of treatment needed. She also questioned the suitability of placebo as the control arm in APRICITY, saying that an excisional procedure or ablation would be more appropriate for patients over the age of 25 years.

“[Finally,] I think it would be important to know the long-term outcomes for patients [in terms of] recurrence rates, need for additional procedures, and cancer risk, [alongside] patient experience as compared to other indicated or appropriate excisional procedures,” Bixel said.

APRICITY was conducted across seven countries (ie, China, Hungary, Germany, Czech Republic, Slovakia, Poland, and the Netherlands) and included 402 women with biopsy-confirmed HSIL. These women were randomly assigned to receive treatment with APL-1702 (5% HAL HCl, photodynamic therapy 125 J/cm² over 4.6 hours) or placebo no more than twice in 6 months.

The modified intention-to-treat population comprised 382 women (median age 29.54 years, 25.6 percent had HSIL area <15 percent, 52.4 percent had CIN3, 61.3 percent HPV 16/18-positive), while the open-label extension population consisted of 216 women (median age 29.86 years, 27.6 percent had HSIL area <15 percent, 41.7 percent had CIN3, 60.2 percent HPV 16/18-positive).