The grade 3 or 4 adverse events observed were cases of autoimmune hepatitis, increased gamma-glutamyl transferase levels, muscle weakness, nausea, and septic shock. However, there were no treatment-related deaths.
In patients who developed any-grade immune-related adverse events of interest, just one – a patient with autoimmune hepatitis – had to have treatment interruption.
All of the responses observed were partial responses. The median time to response was 8 weeks, and the median duration of response was not reached, with a range from about 9 to 44 weeks. The three patients with a response had been in the study for at least 26 weeks as of the data cutoff for analysis.
“Cost is an issue with these drugs,” said attendee Dr. Mark Graham II, an oncologist with Waverly Hematology Oncology, Cary, N.C. “I’m particularly interested in your nonresponders and the fact that we can see pseudoprogression with these drugs. So for the eventual nonresponders, …what is the likely number of cycles that will be necessary to conclude that a patient is not an initial responder?”
That number is difficult to accurately pin down, as patients in the trial were taken off the agent as early as 8 weeks along if they had any evidence of progression, Dr. Rugo said. “I really don’t think we know the answer yet, but if you went out to 16 weeks, all the patients that we saw who were going to respond had responded by 16 weeks.”
An accurate answer will likely require future studies, she added. “I think it’s most complicated in triple-negative disease, where a small phase Ib trial showed a very long median time to response. So this is a good question and it remains to be answered.”
If sufficient tissue is available, the investigators plan to look for other biomarkers of pembrolizumab benefit, such as proliferation markers and intrinsic subtype, according to Dr. Rugo. “Probably those more in-depth investigations are going to occur with future studies, just because of the need to acquire enough tissue to do them. This trial was exploratory,” she said.
Dr. Rugo disclosed that her institution receives research funding from Merck & Co. – the trial sponsor – and Genentech.