Aglatimagene Besadenovec Plus Radiotherapy Improves Disease-Free Survival

Key Takeaways

• Median disease-free survival was not reached with aglatimagene plus valacyclovir and was 86.1 months with placebo plus valacyclovir.
• The phase 3 randomized, double-blind, placebo-controlled trial enrolled 745 men across 51 centres in the USA and Puerto Rico.
• Grade 3 or worse adverse events were reported at similar rates, acute kidney injury was the most common severe event, and no treatment-related deaths occurred.

Adding intraprostatic aglatimagene besadenovec plus valacyclovir to radiotherapy was associated with longer disease-free survival than placebo plus valacyclovir in men with intermediate- or high-risk localized prostate cancer, according to a phase 3 trial. The disease-free survival hazard ratio was 0.70, with a 95% CI of 0.52 to 0.94. Both groups received valacyclovir alongside standard external beam radiotherapy, keeping the comparison focused on intraprostatic aglatimagene exposure. The difference was observed in a blinded comparison against placebo plus valacyclovir added to radiotherapy. This endpoint defined the trial's central efficacy finding.

This multicenter phase 3 trial enrolled adults aged 18 years or older with intermediate- or high-risk localized prostate cancer, ECOG performance status 0-2, and plans for external beam radiotherapy. Across 51 medical centers in the USA and Puerto Rico, 745 men were randomized between Feb 21, 2012, and Sept 9, 2021. Investigators assigned 496 men to aglatimagene plus valacyclovir and 249 to placebo plus valacyclovir through central block randomization. The 2:1 assignment covered three intraprostatic courses of aglatimagene 5 × 10^11 viral particles or matching placebo, stratified by risk category and androgen deprivation therapy use. Radiotherapy used 78 Gy in 2 Gy fractions, 60 Gy in 3 Gy fractions, or 70 Gy in 2.5 Gy fractions, with optional androgen deprivation therapy.

Disease-free survival in the intent-to-treat population was the primary endpoint, and median follow-up at analysis was 50.3 months, with an IQR of 35.2 to 63.3 months. At that analysis, disease-free survival was longer in the aglatimagene group than in the placebo group. Median disease-free survival was not reached with aglatimagene plus valacyclovir and was 86.1 months with placebo plus valacyclovir. The randomized cohort included 591 White men and 121 Black men, as reported in the abstract. These efficacy results showed longer disease-free survival with the aglatimagene regimen.

In the safety population, grade 3 or worse treatment-emergent adverse events occurred in 40 of 479 patients given aglatimagene and 17 of 232 given placebo. Serious adverse events occurred in 28 patients in the aglatimagene group and 17 in the placebo group. Treatment-related serious adverse events were uncommon, affecting eight patients in the aglatimagene group and five in the placebo group. Acute kidney injury was the most common severe event in both groups, and no treatment-related deaths occurred. The authors concluded that adding aglatimagene plus valacyclovir to radiotherapy was associated with longer disease-free survival without increased clinically significant toxicity.