Durvalumab Plus BCG Cut Early Recurrence of High-Risk Bladder Cancer

WASHINGTON — Add-on durvalumab (Imfinzi) reduced the number of early high-risk disease recurrences within the first year in patients with high-risk non-muscle-invasive bladder cancer (NMIBC), according to new analyses from the POTOMAC trial.

The phase III study showed that in that first year, 16% of 339 patients who received durvalumab plus bacillus Calmette-Guérin (BCG) induction and maintenance therapy experienced a high-risk event compared with 20% of 340 patients who received BCG therapy alone, reported Neal Shore, MD, of the Carolina Urologic Research Center in Myrtle Beach, South Carolina.

The median time from randomization to high-risk disease event was substantially longer in the durvalumab arm at 14.1 months versus 8.3 months in the BCG-alone arm.

Moreover, just 45% of those who had a disease event in the durvalumab arm experienced it in the first year compared with 61% in the BCG arm.

Shore also reported that the addition of durvalumab to BCG induction and maintenance therapy resulted in fewer recurrences among BCG unresponsive patients, and fewer cystectomies.

“The data clearly support 1 year of durvalumab in combination with BCG induction and maintenance as a potential new treatment for patients with BCG-naive, high-risk NMIBC, with an appropriate shared decision-making conversation.” he said at the American Urological Association annual meeting.

POTOMAC was done at 116 sites in 12 countries with 1,018 patients, 37% of whom had carcinoma in situ while 65% had papillary disease only. They were randomized to receive durvalumab plus BCG induction and maintenance, durvalumab plus BCG induction only, or standard BCG induction and maintenance alone. Median age was 67-68 years across the three groups, 80% of participants were men, 79% were white, and 18% were Asian.

Initial trial findings showed the durvalumab plus BCG regimen resulted in a 32% reduction in the risk of recurrence of high-risk disease or death by any cause compared with BCG therapy alone (HR 0.68, 95% CI 0.50-0.93, P=0.015), meeting the trial’s primary endpoint.

Shore also reported that BCG-unresponsive high-risk disease recurrences were fewer in the durvalumab group (65% vs 81%). Of those unresponsive patients, fewer proceeded to cystectomy with durvalumab (8% vs 25%). There also were fewer cystectomies in the durvalumab arm (4% vs 6%, HR 0.63, 95% CI 0.31-1.24). And median time to cystectomy was longer in the durvalumab arm (19.0 vs 14.1 months).

In an analysis of the papillary-only population (65% of patients) Shore reported there was a 39% to 52% reduction in the risk of risk-disease recurrence or death across papillary tumor subtypes with durvalumab plus BCG.

Overall survival (OS) showed a trend among the intention-to-treat population in favor of the combination (HR 0.80, 95% CI 0.53-1.20), with no detriment t0 OS observed across papillary subgroups.

Regarding safety, in the overall safety population, any-cause adverse effects (AEs) occurred in 97% versus 91% of patients in the durvalumab and BCG only groups, respectively.

Treatment-related grade 3 or 4 AEs occurred in 21% versus 4% of patients in the durvalumab and BCG groups, respectively. Serious AEs happened in 13% versus 4%. AEs leading to discontinuation occurred in 31% versus 20%. Discontinuations possibly related to durvalumab specifically were 16% versus 0.3%.

For immune-mediated AEs, Shore emphasized that it is “important for our colleagues to become comfortable with these, if you haven’t already.” These AEs of any grade occurred in 27% of the durvalumab arm versus 1% in the BCG arm. Shore noted that the safety profile of combining durvalumab with BCG induction/maintenance in papillary only tumors “was consistent with the overall safety population,” as an equal proportion of patients in those populations had any-grade immune-mediated AEs.

The most common immune-mediated AEs were hypothyroid events (11%), hepatic events (5%), dermatitis/rash (3%), hyperthyroid events (2%), and thyroiditis (2%), most of which were low grade and manageable, with 67% having those AEs resolved by the time of data cutoff, Shore reported.