New and Targeted Therapy for Gastric Cancer: A Focus on Immunotherapy and HER2

Joseph Chao, MD, City of Hope Comprehensive Cancer Center, Duarte, CA, reviews his presentation on new and upcoming targeted agents in gastric cancer, including immunotherapy and HER2-targeted treatments, from the Great Debates and Updates in Gastrointestinal Malignancies virtual meeting in September 2022.

In his presentation, Dr Chao discusses the “era of first-line immunotherapy” for gastroesophageal malignancies, as well as promising trials for HER2 targeted approaches and early-stage diseases. He also touches on the concern of patients with microsatellite stable disease PD-L1 low-expression.

Transcript:

Good day to everybody. I am Joe Chao, a GI medical oncologist and social professor at the City of Hope Comprehensive Cancer Center in Duarte, Southern California. I had recently spoken at the Great Debates and Updates in Gastrointestinal Malignancies, focusing on the topic of Novel and Targeted Agents in Gastric Cancer, both IO and HER2 approaches.

I think we are in the era of first-line immunotherapy, both for HER2-positive and HER2-negative disease in gastroesophageal malignancies. I think though some debates exist, asking, do all patients benefit from first-line immune checkpoint inhibition? I certainly would argue that those patients that have high PD-L1 overexpression or have MSI-high disease, the magnitude of benefit is there to adding PD-1 inhibitors to first line treatment. For HER2-positive disease, we do have an accelerated FDA approval, in terms of adding pembrolizumab to trastuzumab and chemotherapy.

There are certainly concerns about patients with microsatellite stable disease and PD-L1 low-expression, though. I did highlight in my talk some of the recent literature raising concerns about cross-validity of different assays for PD-L1 overexpression. I think we still have a lot of work to find a more composite biomarker, given there may still be some weaknesses in terms of PD-L1 and clearly identifying those patients that don't benefit from first-line immunotherapy with chemotherapy.

But in terms of other HER2 targeted approaches, we do have trastuzumab deruxtecan, mainly in the third-line setting, globally. Though, also in the US, we have accelerated FDA approval for second line. This is based on both randomized data in the third-line setting and single arm, phase 2 data for Western patients with a DESTINY-Gastric02 study, which has shown very promising response rates. But the key is, these are patients who had a revive after first-line treatment, and then subsequently were confirmed to still be HER2-positive. HER2 loss has been recognized as the mechanism of resistance to progression in first-line chemotherapy and anti-HER2 containing regimens.

And I think we hopefully can make some more headway in terms of early-stage disease. I did cover the NEONIPIGA study, a very encouraging phase 2 dataset for MSI-high patients given nivolumab and ipilimumab, having very encouraging pathologic complete response rates. Survival is still early in follow up but does appear very encouraging and hopefully we'll have more follow up studies. There are phase 3 studies in which we're waiting for readout in terms of incorporating IO strategies with perioperative chemotherapy and recyclable disease.

We’re very much looking forward to continuing datasets and new approaches that can hopefully bring about more improved outcomes for our patients affected by gastroesophageal cancer.

Source:

Chao J. “Novel and Targeted Agents in Gastric Cancer (IO and HER2).” Presented at Great Debates and Updates in Gastrointestinal Malignancies; September 21-23; virtual.