Using Antibody-Drug Conjugates in Later-Line HER2+ Gastric Cancer
John L. Marshall, MD, discusses the situations where patients could benefit from fam-trastuzumab deruxtecan-nxki as second-line treatment for locally advanced or metastatic HER2-positive gastric cancer.
John L. Marshall, MD, chief of the division of hematology/oncology at Medstar Georgetown University Hospital, professor of medicine and oncology at Lombardi Comprehensive Cancer Center at Georgetown University, and director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer, discusses the situations where patients could benefit from fam-trastuzumab deruxtecan-nxki (Enhertu) as second-line treatment for locally advanced or metastatic HER2-positive gastric cancer.
Trastuzumab deruxtecan was approved based on the DESTINY-Gastric01 study (NCT03329690) in patients who previously received trastuzumab (Herceptin). In this trial, there was an objective response rate (ORR) of 51% versus 14% with paclitaxel or irinotecan chemotherapy. This shows it can provide better efficacy for patients than recommended second-line chemotherapy options, though it has a unique adverse event profile including risk of interstitial lung disease that must be managed, according to Marshall.
Marshall says that when using this agent following first-line trastuzumab, physicians must decide whether testing for HER2 expression again is needed since it was not required in the trial. Repeating HER2 testing is difficult since it requires another biopsy, though some liquid biopsies could identify HER2 status more quickly and easily. Overall, he says it is better to re-test if possible when considering treatment with a second HER2-targeted agent, but trastuzumab deruxtecan is otherwise a good option.
0:08 | You now have a new tool in the toolbox for the treatment of HER2-positive gastric and gastroesophageal junction cancers. We didn't have that before. So if you were going to give HER2-targeted therapy in [the] first line, you only had your other chemotherapy options. And now you've got into second-line [a] HER2-positive option with trastuzumab deruxtecan. So if you're looking at the patient in front of you and trying to decide, “Do I go with taxane, or irinotecan, or other of the guideline-suggested chemotherapies in second and third line,” you know you've got this compound in hand. [It has a] higher response rate, [and] yes, some toxicity that goes with that. So, in a patient who's not faring well [and] needs a response, this is clearly a good choice in that patient population.
1:00 | One of the controversies that comes up with this agent is: Do you need to repeat HER2 testing in the second line? It wasn't required as part of this clinical trial, and, of course, in other diseases, you do repeat HER2 testing. So I think the answer is best to do it if you can. But it's not easy to do repeat biopsies and repeat HER2 testing. Some liquid biopsies may be able to help you with that. But it's not a requirement in going forward into second line. So if I've got a patient in front of me needs a response needs it in second line, I think the [trastuzumab deruxtecan] angle is a very legitimate choice in that second-line space.