Unmet Needs For Targeted Therapies in Gastroesophageal Adenocarcinoma

Samuel J. Klempner, MD, medical oncologist at Massachusetts General Hospital, discusses unmet needs in patients with gastroesophageal adenocarcinoma when it comes to biomarker-targeted agents.

Studies such as the CheckMate 649 trial (NCT02872116) of nivolumab (Opdivo) and ipilimumab (Yervoy) and the KEYNOTE-590 trial (NCT03189719) of pembrolizumab (Keytruda) have found benefit for many patients who receive an immune checkpoint inhibitor along with chemotherapy.

However, those with low combined positive score (CPS) and low PD-L1 expression do not benefit as much from checkpoint inhibitors. According to Klempner, a major unmet need in this setting is finding novel targeted agents that can provide benefit to these subgroups.

In addition to immunotherapy, HER2-positive disease can be targeted with the monoclonal antibody trastuzumab (Herceptin). Other targets that are currently being explored include the Claudin 18.2 tight-junction protein which can be targeted by the monoclonal antibody zolbetuximab, and FGFR2, which can be targeted with inhibitors such as pemigatinib (Pemazyre). Klempner says there is a pressing need for novel therapies in gastric cancers for patients who lack HER2 or other known targetable biomarkers.

TRANSCRIPTION:

0:08 | There are still a lot of unmet clinical needs for gastroesophageal adenocarcinoma. So, one thing that has been quite reproducible from the available datasets is that the patients with low CPS and low PD-L1 expression are certainly deriving a lesser magnitude, if any, benefit from the addition of checkpoint inhibitors in many patients. And so, how do we expand the benefit of novel therapies to this patient population?

Then moving beyond immunotherapy, there [are] a lot of targets that are currently being explored and hopefully will come to the clinic in the relatively near future. These include things like Claudin 18.2 [and] FGFR2, for which there [are] a substantial amount of data, and then certainly we need novel biomarkers and novel therapies for patients that don't express those biomarkers or biomarkers such as HER2.