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SAN DIEGO -- A novel, noninvasive, photodynamic drug-device combination was efficacious and safe for patients with cervical histologic high-grade squamous intraepithelial lesions (HSIL), a randomized phase III trial showed.

Use of the drug-device known as APL-1702 resulted in a response rate of 41.1% versus 21.7% with placebo (P=0.0001), reported Yue Wang, MD, PhD, of Henan Provincial People's Hospital in Zhengzhou, China, during the Society of Gynecologic Cancer (SGO) annual meeting.

In addition, a higher proportion of high-risk human papillomavirus (HPV) 16- and/or HPV 18-positive patients in the APL-1702 group had clearance of HPV at 6 months (31.4% vs 15.4% with placebo, P<0.05).

Wang also noted that the incidence of treatment-emergent adverse events (TEAEs) was comparable between the APL-1702 group and the control group (56.8% and 56%, respectively), and most TEAEs were mild. Treatment-related adverse events occurred in 31.6% and 26.1%, respectively, and only 1.5% of each group experienced serious adverse events.

"The benefit of a therapy like this is that it is low risk, it's office-based, it doesn't need anesthesia, had very limited treatment-related adverse events that were quite manageable, and doesn't require any anatomic disruption of the cervix, which could have an impact on fertility, cervical stenosis, and pelvic pain," noted SGO discussant Kristin Bixel, MD, of the Ohio State University Comprehensive Cancer Center in Columbus.

However, Bixel questioned whether placebo was an appropriate control arm, and noted that an excisional procedure or ablation would be appropriate for patients over the age of 25. She also said long-term outcomes with APL-1702, as well as patient experience, compared with other appropriate or indicated procedures should be evaluated.

"Additionally, it would be important to consider the cost of this device, especially if retreatment is frequently indicated," she added.

Wang explained that while low-grade squamous intraepithelial lesions (LSIL) usually resolves spontaneously, guidelines for cervical cancer screening generally recommend medical treatment for women with HSIL -- surgical treatments that could result in complications for women of reproductive age.

The device is made of medical-grade silicone and is about the size of a tampon, with a cup-shaped emission light source at the end. It is placed by a gynecologist and then removed by the patient at the end of treatment.

Based on the principles of photodynamic therapy, a photo synthesizer -- in this case 5-hexaminolevulinate (HAL) -- is used in combination with light activation from the device to produce a therapeutic effect.

The double-blind, prospective included 402 patients from 61 sites in China and Europe who were randomized 2:1 to receive APL-1702 or placebo, no more than twice in 6 months.

These patients had a median age of 29.5 years, and the vast majority were HPV-positive (93.3% treated with APL-1702 and 93.8% with placebo). More than half of patients in each group were HPV 16-positive.

Response was defined as normal or LSIL and clearance of HPV 6 months after the first treatment.

Wang and colleagues also conducted analyses of 216 HSIL patients in the APL-1702 group with 6-month efficacy data who entered the open-label extension of the study.

Based on results from the extension population, Wang reported that responses with APL-1702 were durable:

• Of 102 patients who responded at 6 months, 54.9% maintained response until 12 months after first treatment
• 40% of patients who had LSIL histology and non-clearance of baseline HPV at 6 months became responders at 12 months
• The overall response rate at 12 months was 44.4% -- 58.3% of patients had maintained response and 41.7% were new responders

Wang also noted that among the entire study population, the proportion of patients treated with APL-1702 who were HPV-positive at baseline fell to 82.1% at 3 months, 64.8% at 6 months, and 41.4% at 12 months. There was a trend of increasing HPV clearance over time, and up to 12 months.

The most common adverse events were vaginal discharge (13.2% in the treatment arm and 3.7% in the placebo arm), vaginal infection (7.5% and 12.7%), and abdominal pain (7.9% and 3.7%).

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