Jeffrey R. Infante, MD
Avelumab, a fully human PD-L1 IgG1 antibody, demonstrated clinical activity in patients with previously treated, recurrent/refractory ovarian cancer in a phase Ib open-label expansion trial.
Seventy-five patients, 68% of whom had three or more prior therapies, received treatment with intravenous avelumab at 10 mg/kg biweekly. The objective response rate by RECIST criteria was 10.7% (95% CI, 4.7-19.9) after a median follow-up duration of 5 months.
The stable disease rate was 44%, with a disease control rate of 54.7%. The median duration of treatment was 12 weeks, with a median time to response of 9 weeks. The median duration of response was 21 weeks, with 62.5% of responses ongoing.
To learn more about these findings, OncLive
spoke with one of the study authors, Jeffrey R. Infante, MD, director, Drug Development Program, and principal investigator at Sarah Cannon Research Institute.OncLive: What is the significance of this study?Dr Infante
: Avelumab is a PD-ligand inhibitor. This is the first and longest study that has been done in ovarian cancer with these types of immunotherapies to date. The study began in November 2013 and enrolled 75 patients into an ovarian cohort until November 2014.What were the results?
When we looked at this specific ovarian population, the protocol was designed so that, after 23 patients made it through 2 months, the investigators could examine the data. We did see responses in ovarian cancer. This is exciting because, while melanoma and kidney cancer have always been thought to be immunogenic, ovarian cancer has been much more questionable. It was unclear if there would be a benefit. We had responses that were confirmed and patients did well. We had some atypical responses where the tumor looked like it was progressing and then, all of a sudden, it started to respond. That was very unique.
When we looked at how many patients remained on the study or were progression-free after 6 months, the number was approximately 33%. Therefore, about one-third of the patients were still getting benefit after 6 months. This is very exciting. We have new options for this patient population with this well-tolerated immunotherapy.What is the safety profile of avelumab?
From a tolerability standpoint, the PD-L1 inhibitors are, overall, very similar to what has been seen with the PD-1 inhibitors. The majority of these patients do well. There are a small number of patients, around 10% to 15%, who have side effects that are autoimmune-related. These include diarrhea, nausea, and skin rashes, but these are usually manageable. There are a few patients who have infusion-related reactions, but they are tolerated with antihistamines. The vast majority of patients don’t feel as if they are getting standard chemotherapy. Most of the side effects are grade 1/2 and are manageable and mild. There were no serious adverse events that were thought to be treatment-related in this study.What are the next steps in this research?
Avelumab, as a PD-ligand inhibitor, is being studied in multiple tumor types, not just ovarian. There are other cohorts that are currently enrolling patients. The next steps are likely combination strategies, with immunotherapies being a way to continue to raise the bar. If we can take that number of 33% PFS at 6 months, and increase it by 10% or 15% every time, that would be good. The key will be the tolerability. Therefore, I think much of the focus will be on combinations that are both tolerable and effective.What is the potential impact of this study on patients with recurrent or refractory ovarian cancer?
Patients with ovarian cancer often respond to many therapies, but they are often transient responses. Patients can do well, but every time they respond to a therapy they become less durable and, over time, the tumors become more and more refractory. Avelumab would be a completely different mechanism than any other drug that has been approved in ovarian cancer. In this trial, the majority of patients had more than four prior therapies; they were fairly heavily pretreated. If this therapy is able to work here, we should probably start moving it up into the sequence in ovarian cancer treatment, especially with the tolerability and durability that we are seeing.