News
Video
Other Clinical Trials With Chemoimmunotherapy in Biliary Tract Cancers
Expert perspectives on the KEYNOTE-966 and IMbrave151 clinical trials and novel chemoimmunotherapy combination strategies in biliary tract cancers.
Transcript:
Milind Javle, MD: Laura, you mentioned that the results from TOPAZ-1 were confirmed by the KEYNOTE-966 trial with gemcitabine, cisplatin, and pembrolizumab. Give us a brief overview of this study for individuals who aren’t aware of the results. Then you and I can reflect on how we’re going to decide between these regimens.
Laura W. Goff, MD: The first question is a little easier than the second. The KEYNOTE-966 trial was looking at the combination of gemcitabine-cisplatin with pembrolizumab in patients with advanced biliary tract cancer who hadn’t received previous treatment. The clinical trial design was slightly different from that of TOPAZ-1, and it was done in a slightly different patient population. The key difference was that gemcitabine-cisplatin was continued along with pembrolizumab. But other than that it was quite similar, looking for benefit in progression-free survival [PFS] and overall survival. At the time of report, a statistically significant benefit was seen in overall survival. It wasn’t clearly seen in progression-free survival, but the benefit was seen as time went on.
What does that mean? To some degree, I’m still digesting it. The main takeaway from that report was that chemoimmunotherapy really does have a role in biliary tract cancers. I’d still like to determine which specific patients or subsets of patients we can attribute the benefit to, but it helps me feel like TOPAZ-1 wasn’t just a fluke. Maybe I harbored some secret suspicions that that might have been the case.
What are we going to do? There are a couple of questions. Is there a difference between pembrolizumab and durvalumab? Should we continue chemotherapy? I don’t know that I have a data-driven answer. My impression has generally been that the checkpoint inhibitors are pretty similar across drugs. Pembrolizumab targets PD-1, and durvalumab targets PD-L1. Sometimes there are differences made of that. This doesn’t seem to be showing that. Both probably seem OK.
Then there’s the question of chemotherapy. Historically, I’ve felt that there was a benefit to continuing chemotherapy as long as patients have tolerated it. I still feel that way, although there wasn’t a market benefit seen in the KEYNOTE-966 that I was thinking that we might see. It reassures me that if patients are having issues with cytopenias or for other reasons, [we should] stop chemotherapy. I feel a little more comfortable doing so.
Milind Javle, MD: I agree. I’m not sure there’s a huge difference. The survival difference was similar. I’m also loving the idea of no chemotherapy after 6 months. By 6 months, they’re done. You should never compare across studies, but you do. I was hoping to see what the difference would be with single-agent gemcitabine with an immunotherapy with a checkpoint inhibitor vs checkpoint inhibitor alone. Statisticians would be very upset with this comparison. But as a practicing physician, I don’t know if I see a huge difference.
Laura W. Goff, MD: The monthly dosing of durvalumab that they switch to in TOPAZ-1 is nice for patients. You and I spend a lot of time talking to our patients and hearing from them, and the idea that they could get back to living their life with a monthly injection is quite valuable. Time off chemotherapy is very valuable time.
Another study presented at [ASCO] GI [American Society of Clinical Oncology Gastrointestinal Cancers Symposium] in January was the IMbrave 151, which looked at atezolizumab with or without bevacizumab along with gemcitabine-cisplatin. Tell us about that study.
Milind Javle, MD: The combination of atezolizumab, which is a PD-L1 [inhibitor], with the VEGF inhibitor bevacizumab has led to great gains in hepatocellular cancer. Clearly, the VEGF inhibitor seems to have a favorable change in the immune microenvironment. The study had 2 arms. It was a phase 2 randomized study, unlike the other 2 studies, which are large phase 3 trials. This phase 2 study combined gemcitabine-cisplatin with atezolizumab and placebo, or gemcitabine-cisplatin with atezolizumab with bevacizumab. The primary end point of this study was progression-free survival. I imagine they’re going to use this trial and the figures to plan a subsequent phase 3 trial.
Surprisingly, there was no statistical difference of survival difference in the progression-free survival between the 2 arms. The PFS looked a little more than what we’ve historically seen, but I’m not sure either arm was impressive enough. I’m curious what would have happened if 1 of those arms was compared with gemcitabine-cisplatin, as we saw in the other trials. In both trials, TOPAZ-1 and KEYNOTE-966, the progression-free survival was similar: several months or so. But overall survival was impacted…. I don’t know what to make of that study except that the addition of bevacizumab wasn’t that favorable. I’m not sure if this path is going forward in further development.
Laura W. Goff, MD: I agree.
Transcript edited for clarity.
