! I’m your host today, Caroline Seymour.

 provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

We had the pleasure of speaking with John L. Marshall, MD, chief in the Division of Hematology/Oncology at Medstar Georgetown University Hospital, professor of medicine and oncology, and director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer at Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, who discussed the evolving treatment landscape of HER2-targeted treatment strategies in colorectal cancer.

 is an important target in colorectal cancer for which there are several approved and investigational agents, explained Marshall. Although the optimal HER2-targeted strategy has yet to be defined, antibody-drug conjugates have shown early promise in this subset of patients.

Marshall explained that trastuzumab deruxtecan, which received an accelerated approval from the FDA for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti—HER2-based regimens in the metastatic setting, has shown early signals of activity in colorectal cancer.

In order to move the needle forward in colorectal cancer, HER2 testing will be essential, according to Marshall.

Listen on to hear Marshall discuss the necessity of identifying patients with HER2-positive colorectal cancer and the work being done to better elucidate effective targeted treatments for patients.

Videos

We had the pleasure of speaking with John L. Marshall, MD, who discussed the evolving treatment landscape of HER2-targeted treatment strategies in colorectal cancer.

Talking HER2-Targeted Therapy With Dr. Marshall

We had the pleasure of speaking with Ian Chau, MD, FRCP, consultant medical oncologist within the Gastrointestinal and Lymphoma units at The Royal Marsden Hospital, and Reader at the Institute of Cancer Research in London and Surrey, United Kingdom, who discussed the state of HER2-directed therapy in gastric/gastroesophageal cancer.

Approximately 20% to 22% of patients with gastric/GEJ cancer will have HER2-positive tumors, said Chau. As such, HER2 has become one of the guideline-recommended markers that should be tested for, preferably with a broad molecular panel, per the National Comprehensive Cancer Network, added Chau.

A patient with HER2-positive gastric/GEJ cancer should receive chemotherapy and trastuzumab. However, limited options exist for those who progress on these agents. However, antibody-drug conjugates, specifically trastuzumab deruxtecan, could help fill this unmet need, according to Chau. According to topline findings from the phase II DESTINY-Gastric01 trial, the HER2-targeted ADC showed a statistically significant improvement in objective response rate and overall survival versus physician’s choice of paclitaxel or irinotecan in patients with advanced HER2-positive gastric/GEJ cancer who progressed on 2 prior therapies, meeting the primary end point of the study. Additionally, the safety profile of the agent proved to be consistent with prior findings reported from the phase I study.

Data from the phase II study will be presented at an upcoming medical meeting. Also anticipated, are data from the phase II DESTINY-Gastric02 trial, in which patients with unresectable or metastatic HER2-positive gastric/GEJ cancer who progressed on or after a trastuzumab-based regimen will receive trastuzumab deruxtecan.

Listen on to hear Chau discuss HER2 testing in gastric/GEJ cancer and several HER2-targeted strategies under evaluation

We had the pleasure of speaking with Ian Chau, MD, FRCP, who discussed the state of HER2-directed therapy in gastric/gastroesophageal cancer.

Talking HER2-Targeted Therapy With Dr. Chau

We had the pleasure of speaking with Jaffer Ajani, MD, professor of medicine, and internist in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, who discussed some of the investigational HER2-targeted treatment strategies with trastuzumab, antibody-drug conjugates, and bispecific antibodies that are under investigation in gastrointestinal malignancies.

Several clinical trials are ongoing in gastric cancer and colorectal cancer and through this research, investigators are seeking to define the optimal HER2-targeted approach, explained Ajani. For example, in the phase III KEYNOTE-811 trial, previously untreated patients with advanced HER2-positive gastric/gastroesophageal cancer will be randomized to receive the combination of trastuzumab and chemotherapy plus pembrolizumab or placebo.

Additionally, in an ongoing phase II trial, investigators are evaluating the safety and efficacy of combining the bispecific antibody ZW25 with physician’s choice of chemotherapy in patients with previously untreated, advanced HER2-positive GEJ cancer.

Following encouraging data with the ADC DS-8201a in patients with unresectable or metastatic HER2-positive gastric/GEJ cancer who had received at least 2 prior therapies, the drug is being evaluated as second-line therapy in patients with unresectable or metastatic disease in the phase II DESTINY-Gastric02 trial.

Moreover, the monoclonal antibody margetuximab is under evaluation as frontline therapy in the multiarm phase II/III MAHOGANY trial in combination with PD-1 and anti—LAG-3 inhibition in patients with HER2-positive gastric/GEJ cancer.

In colorectal cancer, DS-8201a and ZW25 have shown the most potential, said Ajani; however, where these agents will play a role in the treatment landscape has yet to be determined.

Listen on to hear Ajani discuss some of the HER2-targeted strategies that are under exploration in gastric/GEJ cancer and colorectal cancer, the potential downsides of bulk tumor testing, and the promise of liquid biopsies in the space.

We had the pleasure of speaking with Jaffer Ajani, MD, who discussed some of the investigational HER2-targeted treatment strategies with trastuzumab, antibody-drug conjugates, and bispecific antibodies that are under investigation in gastrointestinal malignancies.

Talking HER2-Targeted Therapy With Dr. Ajani

We had the pleasure of speaking with Ryan Corcoran, MD, PhD, associate professor of medicine at Harvard Medical School, gastrointestinal oncologist, director of the Gastrointestinal Cancer Center Program, and scientific director of the Termeer Center for Targeted Therapy at the Massachusetts General Hospital Cancer Center, who discussed key takeaways regarding the use and investigation of HER2-targeted therapies in gastrointestinal malignancies.

The most established role of HER2-targeted therapy is in gastric cancer, wherein approximately 20% of patients will have HER2 overexpression or amplification, said Corcoran. In colorectal cancer, HER2 amplification is less common, found in approximately 4% of patients. Despite this disparity, Corcoran recommends testing these for 

 with a comprehensive next-generation sequencing panel so that these patients can be directed to appropriate clinical trials, including but not limited to, those with antibody-drug conjugates and bispecific antibodies.

Among these investigational treatment strategies, trastuzumab deruxtecan has demonstrated encouraging phase I data and positive topline findings from the phase II DESTINY-Gastric01 trial. Specifically, topline data with the agent showed improved overall survival versus chemotherapy in patients with heavily pretreated HER2-positive gastric/gastroesophageal cancer. While the data from the phase II trial have yet to be presented, data from the phase I experience showed that the agent led an objective response rate of 43.2% and a disease control rate of 79.5% in patients with advanced gastric/GEJ cancer who had progressed on at least 2 prior regimens, including trastuzumab, 5-FU, and platinum chemotherapy.

Listen on to hear Corcoran discuss the current testing standards and practice patterns surrounding the treatment of HER2-positive gastrointestinal malignancies and provide insight on the current understanding of acquired resistance to HER2-directed therapy.

We had the pleasure of speaking with Ryan Corcoran, MD, PhD, who discussed key takeaways regarding the use and investigation of HER2-targeted therapies in gastrointestinal malignancies.

Emerging Advances in Gastrointestinal Cancers | Supplements and Featured Publications

Talking HER2-Targeted Therapy With Dr. Marshall

Talking HER2-Targeted Therapy With Dr. Chau

Talking HER2-Targeted Therapy With Dr. Ajani

Talking HER2-Targeted Therapy With Dr. Corcoran