Zev Wainberg, MD
A number of clinical trials have been examining the potential of immunotherapy agents in the field of gastric cancer, though several questions remain regarding what role this type of therapy could actually have.
The phase II FAST trial, for example, examined the monoclonal antibody IMAB362 in gastric cancer. The agent improved median progression-free survival (PFS) by 3.1 months and median overall survival (OS) by 4.8 months in combination with a 3-drug chemotherapy regimen. This treatment was compared with chemotherapy alone in results of the FAST trial, where it was shown that the former's benefit was more pronounced among patients with high expression levels of CLDN18.2.
Secondly, the JAVELIN trial is currently investigating avelumab in patients across multiple solid tumor types who progressed on more than 2 lines of prior therapy, or had received 1 line of chemotherapy without progression. Data show that, of the 75 patients with gastric cancer/gastroesophageal junction who were treated with avelumab, responses were observed in 7 patients. PD-L1 expression was evaluable in 55 patients, including in 3 patients with a response. Median PFS in patients who had received 2 or more prior lines of therapy was 36 weeks (95% CI, 6.0-36.0) for PD-L1–positive patients and 11.6 weeks for PD-L1−negative patients. Among patients who had received 1 prior line of chemotherapy, the median PFS was 17.6 weeks for PD-L1–positive patients and 11.6 weeks for PD-L1–negative patients.
In an interview with OncLive
, Zev Wainberg, MD, an assistant professor of Medicine at UCLA and co-director of the UCLA Gastrointestinal Oncology Program, discusses a plethora of immunotherapy agents, such as pembrolizumab (Keytruda), durvalumab, avelumab, and apatinib, for the treatment of patients with gastric cancer, as well as a number of ongoing clinical trials in this space.
OncLive: Can you discuss the clinical trial you're involved in with pembrolizumab?
That has been studied in several different settings, including the third-line setting, for which preliminary evidence of activity has already been presented in small patient numbers at previous meetings. That data has been reported now a few times, with response rates and some of the activities of this agent in a group of patients who have not historically responded very well. These are the third-line typical patients, or advanced patients with metastatic gastric cancer.
The bigger study that's being done is to confirm those results in a very large number of patients with that profile. Additionally, there are randomized trials going on with that agent in both the first-line setting—so newly diagnosed patients with metastatic gastric cancer, either by itself or in combination with chemotherapy—and in second-line metastatic gastric cancer, randomized, and with chemotherapy as the control arm.
We have, to my knowledge, at least 3 very large studies looking at pembrolizumab in gastric cancer. These are 3 very large, international trials with about 100 patients each trials.
Thus far, does it seem like a promising agent in this space?
I think the hints of activity in these small groups suggest that it is promising, or this group of therapies is promising. It remains to be seen who these patients are; certainly not a large number of them, but rather the minority of them, do respond. There is this group of patients that respond, and these things really need to be reproduced in a much larger set of data to be confident that it's real.
Has PD-1 positivity been investigated in this space?
That's one of the factors, and PD-L1–positive staining is one of the criteria for at least 2 of the trials that I mentioned. It hasn't been worked out to the extent that it has in lung cancer, and we don't even know, to be fair, what percentage of patients are PD-L1–positive in gastric cancer. It is one of the criteria that are used, and on some level, there does seem to be this suggestion that if one doesn’t have staining of the antigen, the likelihood of the response is very low.
What about PD-L1 agents? Do you see potential for that class of drugs?
On some level, there have already been reported results from the JAVELIN trial with avelumab, and there have been reported results of durvalumab with gastric cancers. We're seeing a little more than anecdotal responses in this group of patients that have 10% or 20% responses. I don't think it's going to be pembrolizumab that's going to produce the responses here. I think if it's a true phenomenon in gastric cancer, and we've already seen it with nivolumab as well, then it won't be these one or two drugs. It's going to be across the board.