Transcript:
Yelena Janjigian, MD: I'm Dr. Yelena Janjigian, Associate Attending Physician, Associate Professor, and Chief of Gastrointestinal Oncology Service at Memorial Sloan Kettering in New York City. It's a pleasure this year at the ESMO World GI, virtually, to discuss four important abstracts. Despite virtual attendance, this was a very informative and exciting meeting.
The overview of the four abstracts, including HER2 targeting in metastatic and locally advanced esophageal and gastric cancer with DESTINY-Gastric01 Study looking at trastuzumab deruxtecan in patients with heavily pretreated HER2-positive gastric cancer.
We then discussed RTOG 1010 with trastuzumab plus chemo-radiation in HER2 targeting in locally advanced disease. RTOG 1010 trastuzumab therapy trial failed to show benefit for addition of trastuzumab to chemo-radiation in esophagus cancer, leaving us wanting more and wondering how best to target this disease in perioperative setting.
It's clear to do a randomized trial in this setting is challenging and will take a long time to accrue the patients. HER2 is quite heterogeneous in this population. Therefore, it's very important to consider patient selection for future trials.
At Memorial Sloan Kettering, we're exploring using liquid tumor biopsies of circulating tumor DNA to select patients after chemo-radiation and surgery. If patients have persistent circulating tumor DNA despite curative resection, and have HER2-positive esophageal or gastric cancer, were then randomized to receive trastuzumab or trastuzumab in combination with immunotherapy, pembrolizumab.
In HER2-negative space, there were two trials looking at sequencing of immunotherapy and what role it would have in later lines of therapy.
Interesting subset analysis in KEYNOTE-061 data, which was a second-line chemotherapy or pembrolizumab study, looked at whether or not patients who received pembrolizumab and then went on to receive chemotherapy actually had better outcomes than those patients who did not get pembrolizumab and were receiving chemotherapy alone.
Although it's provocative data, interesting, and worth further exploration, it's not definitive. As you know, subgroup analysis and non-preplanned subgroup analysis often have many biases introduced to them. Although it's interesting data, it's not yet really changing practice.
Lastly, we also reviewed data from nivolumab in observational study, the DELIVER Study, looking at real-world examples and real-world data in large observational study of nivolumab in second and third-line therapy, again, in PD-L1 unselected population, where nivolumab is approved in Asia for use regardless of PD-L1 status.
There, their overall response rate was lower than what's reported in the ATTRACTION-2 Study, again, showing that in real-world data where patients may be presenting more advanced clinical symptoms with ascites and large volume of peritoneal carcinomatosis, in patients who are not selected for biomarkers such as MSI, BV, or high PD-L1 expressor, their response to anti-PD-L1 therapy alone may be relatively modest.
The survival data from that population was not yet mature. What we see with immune checkpoint inhibitors often, even though perhaps the median overall survival or progression-free survival is relatively modest, the long-term survival in this nice tail on the curve is what drives the benefit in subgroups of population.
