As reported in The Lancet Oncology by DeWeese et al, the phase III PrTK03 trial has shown improved disease-free survival with the addition of aglatimagene besadenovec (aglatimagene) to valacyclovir in patients receiving standard radiation therapy for localized prostate cancer. Aglatimagene is an intratumoral adenoviral gene therapy that delivers the HSV-tk gene, enabling conversion of a prodrug, ie, valacyclovir into a cytotoxic metabolite that induces tumor cell death by disrupting DNA replication and repair.
Study Details
In the U.S.–Puerto Rican double-blind trial, 745 patients were randomly assigned 2:1 between February 2012 and September 2021 to receive three courses of intraprostatic aglatimagene (5 × 10¹¹ viral particles) plus valacyclovir (n = 496) or placebo plus valacyclovir (n = 249). All patients received standard-of-care external beam radiation therapy (EBRT) at 78 Gy in 2 Gy fractions or hypofractionated EBRT at 60 Gy in 3 Gy fractions or 70 Gy in 2.5 Gy fractions with optional androgen-deprivation therapy. The primary endpoint was disease-free survival.
Key Findings
Median disease-free survival was not reached (95% confidence interval [CI] = 121.78 months to not reached) in the aglatimagene plus valacyclovir group vs 86.1 months (interquartile range = 29.7–143.0 months) in the placebo plus valacyclovir group (hazard ratio [HR] = 0.70, 95% CI = 0.52–0.94, P = .016).
Adverse events of grade 3 or worse occurred in 8% of the aglatimagene plus valacyclovir group and 7% of the placebo plus valacyclovir group, most commonly acute kidney injury in 2% of each group. Treatment-related serious adverse events occurred in 2% of the aglatimagene plus valacyclovir group (acute kidney injury in four patients, pyrexia in two, and influenza-like symptoms and urinary retention in one each) and in 2% of the placebo plus valacyclovir group (acute kidney injury in four patients and increased creatinine levels and skin rash in one each). No treatment-related deaths were reported.
The investigators concluded: “Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity.”
Paul P. Tak, MD, PhD, of Candel Therapeutics, Needham, Massachusetts, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Candel Therapeutics and U.S. National Institutes of Health. For full disclosures of the study authors, visit thelancet.com.
