Safety Data from JAVELIN Bladder 100

Jeanny Aragon-Ching, MD: We saw toxicities in the JAVELIN Bladder 100 trial. Although toxicities are seen with avelumab, I would say that most were in line with what you would expect for the use of checkpoint inhibitors in clinical practice. There are 2 general categories of adverse events. One would be the treatment-emergent adverse events [TEAEs], which are any AEs [adverse events], any toxicity that happens, regardless of whether it’s immune related or not.

For this, fatigue is one of the most common we’ve seen in JAVELIN Bladder 100, as well as pruritus and UTI [urinary tract infection], although I would say that some of these may be more related to the disease process itself rather than the drug. There were no grade 4 or 5 AEs, so that is comforting. The treatment-related AEs led to discontinuation rate of 12%.

That’s a reasonably good number. The use of high-dose steroids, which is defined as 40 mg or more of prednisone, was seen in about 9%. That is a reasonable treatment-related AE profile for any drug. One peculiar thing I would say about the use of avelumab is that there is a higher incidence than most of the checkpoint inhibitors of infusion-related reactions. It occurred in 10% of patients in the JAVELIN Bladder 100.

Shilpa Gupta, MD: For grade 2 pneumonitis, which is a serious condition, we obviously hold the immunotherapy and start the patients on steroids. If the patients need to be admitted, then we do that. Most patients improve with steroids. Depending on the severity, we make a decision once everything has resolved; most often, we don’t we challenge with the immunotherapy.

Jeanny Aragon-Ching, MD: The adverse effects we saw from avelumab in the JAVELIN Bladder 100 are in line with what we were seeing in the second-line treatment for metastatic urothelial cancers. In the earlier-phase trials for the second-line treatment and beyond, this seems to be a bit more with infusion-related reactions, close to about 30%, which we did not really see in JAVELIN Bladder 100. Other than that, it’s comparable.

Grade 3 or more AEs that were associated with avelumab, including UTI, anemia, hematuria, and fatigue—a lot of them may be related to the disease process itself. It is well known that patients with bladder cancer, especially if they did not get primary treatment because they were metastatic at the time of initial medical assessment, would not have undergone cystectomy. Some of them may present with hematuria. Now it is important to note that none of these treatment-related adverse events, albeit grade 3 or more, had more than 5% in terms of incidence and prevalence. Remember, too, that these were TEAEs, so they’re not necessarily related to immune-related toxicity. It was any AE that happened within the trial.

Transcript Edited for Clarity