Michael K. Gibson MD, PhD, research director, Translational Research in Head and Neck Oncology, Vanderbilt Health, associate professor of medicine, Vanderbilt-Ingram Cancer Center, discusses the importance of addressing unmet needs related to treatment for patients with gastrointestinal (GI) cancers.

Despite advancements being made across the GI cancer treatment arena, unmet needs remain. The ultimate goal is cure, Gibson begins, adding that this is the main unmet need and bar that investigators are continuing to try to overcome. 

One of these areas of concern is the search for available targets for clinicians to investigate, Gibson expands. Moreover, how to combine or sequence the drugs available for the current 4 markers of interest in the GI space remains a challenge, Gibson says.

To address this area of concern, Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center, and colleagues launched the phase 3 KEYNOTE-811 trial (NCT03615326), investigating patients who have advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with overexpression of HER2, Gibson continues. This trial produced what is now the standard-of-care treatment for this patient population of chemotherapy plus immunotherapy, which in this case is pembrolizumab (Keytruda). It is now known that there is plausibility in further investigating combinations and sequencing currently known targets. With additional investigations into this arena, clinicians will be able to provide patients with better and effective therapies down the road, Gibson concludes.

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Michael K. Gibson MD, PhD, discusses the importance of addressing unmet needs related to treatment for patients with gastrointestinal cancers.


Dr Gibson on Addressing Remaining Unmet Needs in GI Cancers

Michael K. Gibson MD, PhD, research director, Translational Research in Head and Neck Oncology, Vanderbilt Health, associate professor of medicine, Vanderbilt-Ingram Cancer Center, discusses advancements in the identification of key biomarkers for patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, and the subsequent development of biomarker-driven therapeutics in this disease space.

Several decades of laboratory research has contributed to the identification of four key biomarkers expressed on the surface of tumor cells in adenocarcinoma, Gibson begins. These include HER2, Claudin 18.2, PD-L1, and 

HER2 was the first actionable target to be identified and targeted in gastric cancer following the read out of the phase 3 ToGA trial (NCT01041404) in 2010. This randomized controlled trial investigated the use of trastuzumab (Herceptin) in combination with chemotherapy vs chemotherapy alone as a first-line treatment for HER2-positive, gastric/GEJ adenocarcinoma. Results from this trial showed that the experimental regimen was highly effective in this patient population, and have supported subsequent use of HER2-targeted options in this space.

Improved molecular characterization of gastric cancer has allowed for the identification of the remaining 3 biomarkers. Claudin 18.2, PD-L1, and 

 mutations or alterations are considered more practical and emerging targets for therapeutic development, Gibson continues.

Currently, there is a significant need for the incorporation of targeted approaches in clinical practice for adenocarcinoma aside from first-line anti-HER2 therapy and second-line anti-VEGF therapy. Targeting these alterations may confer a higher degree of benefit for patients with adenocarcinoma, thereby improving patient outcomes, he explains. Moreover, the ability to identify more viable cell-surface markers of this disease and potentially develop novel monoclonal antibodies to target them may result in a shift in the treatment landscape, Gibson concludes.

Michael K. Gibson MD, PhD, discusses advancements in the identification of key biomarkers for patients with gastric or gastroesophageal junction adenocarcinoma, and the subsequent development of biomarker-driven therapeutics in this disease space.


Dr Gibson on Advancements in Biomarker Identification in Gastric/GEJ Adenocarcinoma

Michael K. Gibson MD, PhD, research director, Translational Research in Head and Neck Oncology, Vanderbilt Health, associate professor of medicine, Vanderbilt-Ingram Cancer Center, discusses current and emerging biomarkers in the treatment of patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma.

® State of the Science Summit™ on gastrointestinal (GI) cancers, Gibson provided an overview of the biomarkers that currently help inform treatment decisions for patients with gastric/GEJ cancer in clinical practice, along agents for 2 biomarkers for agents in late-stage clinical trials that could affect the treatment landscape for patients with gastric/GEJ adenocarcinoma.

Under the umbrella of currently approved treatment, immunotherapy is now a viable option for patients with gastric/GEJ adenocarcinoma. For example, 

the FDA approved nivolumab (Opdivo) to be combined with select types of chemotherapy

 for the frontline treatment of patients with advanced or metastatic gastric cancer, GEJ cancer, and esophageal adenocarcinoma, in April 2021.

Additionally, trastuzumab (Herceptin) is approved for patients with HER2-overexpressing metastatic gastric/GEJ adenocarcinoma who have not received prior treatment for metastatic disease. Furthermore, fam-trastuzumab deruxtecan has also been approved for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric/GEJ adenocarcinoma who have received a previous trastuzumab-based regimen.

The additional 2 targets with agents that are awaiting final data and review from regulatory agents are Claudin 18.2 (CLDN18.2) and FGFR2b, Gibson expands. In the phase 3 SPOTLIGHT trial (NCT03504397), zolbetuximab plus mFOLFOX6 significantly improved progression-free survival and overall survival (OS) vs placebo/mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.

The phase 3 FORTITUDE-101 trial (NCT05052801) is investigating the combination of the monoclonal antibody bemarituzumab plus chemotherapy vs placebo plus chemotherapy in patients with 

-positive advanced gastric/GEJ adenocarcinoma.

Michael K. Gibson MD, PhD, discusses current and emerging biomarkers in the treatment of patients with gastric or gastroesophageal junction adenocarcinoma.


Michael K. Gibson MD, PhD

Articles

Dr Gibson on Addressing Remaining Unmet Needs in GI Cancers

Dr Gibson on Advancements in Biomarker Identification in Gastric/GEJ Adenocarcinoma

Dr Gibson on Current and Emerging Biomarkers in Gastric/GEJ Adenocarcinoma