“This has important implications for patients, given the high costs associated with prolonged courses of therapy,” she says, noting it’s more than monetary. “I often think about the time spent away from work and family for my patients, who sometimes stay on treatment for years.”
As professor of medicine and co-director of the UCLA gastrointestinal oncology program, Zev Wainberg, MD, is aware that staying abreast of new actionable biomarkers can be tough.
“There are so many cancers. Even in gastrointestinal cancers, there are so many different options,” he says.
“Pathologists have challenging jobs because we ask them to do a lot of tests and sometimes we don’t provide the reason why we’re doing that.” Some biomarker tests are more important than others, he acknowledges.
Those who need a primer on GI biomarkers can attend “Promising New Platforms and Targets in the Management of Gastroesophageal Cancers,” where Dr. Wainberg will review validated and emerging therapeutic biomarkers in gastroesophageal cancer, as well as the main clinical trial findings of the past year. He will also discuss promising novel targets, such as Trop-2 and c-MET.
“If you look at the clinical data, most people will argue that the most important thing to get from any and all samples is MSI-high/mismatch repair protein immunohistochemistry, from the pathological perspective, because that has the most impact,” he says. “If you only have one IHC test, you go with that.” HER2 likely would be next, followed by PD-L1 and claudin 18.2. Nuances from patient to patient are a given. “But those prioritization plans for patients are important.”
At UCLA, “mismatch repair IHC is done on just about every single GI tumor,” he says.
Gastroesophageal cancer has a number of validated targets. “We’ve got more emerging data with immunotherapy, particularly the checkpoint inhibitors in advanced disease patients,” Dr. Wainberg says. “We’ve also got in earlier phase studies validation of durvalumab, which is a PD-L1 inhibitor, with chemotherapy in perioperative management of gastric cancer.” And more data are likely to come on the importance of immunotherapy in the MSI-high patient population, “which is quite small but still represents a very important group of patients,” he says. “Those studies are ongoing.”
More data on HER2 inhibition also has recently been published, specifically on the validation of trastuzumab deruxtecan, “mostly in second line [therapy] for now,” he says. In frontline therapy, pembrolizumab is an emerging treatment option following release of the long-term results of the KEYNOTE 811 trial. And the bispecific antibody zanidatamab is a new player, he says. That data has yet to be published, but it shows that chemotherapy plus zanidatamab, with or without the PD-L1 inhibitor tislelizumab, had a positive effect on overall survival.
Other trials saw disappointing data last year, he says. “I would say [the biomarker] FGFR2B so far has been disappointing with respect to the validation of bemarituzumab, which had a positive phase two study but a negative phase three study. It’s a bit of a confusing data set,” he says, but for the moment, the biomarker should not be considered actionable.
Claudin 18.2, meanwhile, now has validation in the frontline setting. “And several large studies have been launched, both with zolbetuximab and immunotherapy in the frontline, along with other mechanisms to block claudin 18.2 with antibody-drug conjugates,” he says. Those trials are rapidly approaching recruitment goals in second-line therapy and frontline trials are being launched as well.
In general, does he see the need for greater access to biomarker testing?
“It’s still not uniform,” he says.
Charna Albert is CAP TODAY senior editor.