Geoffrey Y. Ku, MD, medical oncologist, head, Esophagogastric Section, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the efficacy of zanidatamab (ZW25) plus standard chemotherapy in patients with HER2-positive gastroesophageal adenocarcinoma ​(GEA) in the ongoing phase 2 ZW25-201 trial (NCT03929666).

Overall, zanidatamab in combination with various chemotherapies has been shown to elicit high response rates of 75%, as well as a favorable disease control rate of 89%, in patients with HER2-positive GEA, Ku says. These results favorably compare with the historical data expected with trastuzumab (Herceptin) and chemotherapy alone, Ku explains 

Moreover, in addition to high response rates, the duration of response was encouraging as well at a median of 16.4 months, Ku continues. However, it is believed that responses can deepen over time because and there have several patients have gone on to achieve a complete response, Ku concludes.

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Geoffrey Y. Ku, MD, medical oncologist, discusses the efficacy of zanidatamab plus standard chemotherapy in patients with HER2-positive gastroesophageal adenocarcinoma in the ongoing phase 2 ZW25-201 trial.


Dr. Ku on the Efficacy of Zanidatamab Plus Chemotherapy in HER2+ Gastroesophageal Adenocarcinoma 

Geoffrey Y. Ku, MD, medical oncologist, head, Esophagogastric Section, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the rationale to evaluate zanidatamab in combination with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma (GEA). 

In the phase 1 ZW25-101 trial (NCT02892123), zanidatamab, a bispecific, IgG1-like antibody, demonstrated durable responses and good tolerability when used as monotherapy in patients with heavily pretreated advanced or metastatic HER2-expressing GEA, Ku explains. The confirmed overall response rate was 33% among 35 patients in this population, and the median duration of response was 6 months. 

These results served as the basis for the ongoing phase 2 ZWI-ZW25-201 trial (NCT03929666), which is evaluating zanidatamab in combination with physician’s choice of standard frontline chemotherapy in patients with unresectable, locally advanced, or metastatic HER2-expressing GEA, Ku concludes.

Geoffrey Y. Ku, MD, discusses the rationale to evaluate zanidatamab in combination with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma. 



Dr. Ku on Evaluating Zanidatamab Plus Chemotherapy in HER2-Expressing GEA  

Geoffrey Y. Ku, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the role of durvalumab (Imfinzi) in the treatment of patients with gastric cancer.

There remains a lack of clarity on whether PD-L1 inhibitors like durvalumab, atezolizumab (Tecentriq), and avelumab (Bavencio) are comparable with PD-1 inhibitors like pembrolizumab (Keytruda) and nivolumab (Opdivo). These drugs inhibit the same axis, but it is unknown if they have the same activity. Recent studies have looked at PD-L1 inhibition in gastric cancer, particularly with avelumab, but these trials were relatively disappointing, Ku says.

In a 5-cohort study presented at the 2019 AACR Annual Meeting, durvalumab was evaluated as a second- and third-line treatment for patients with gastric cancer. Specifically, researchers were trying to use an interferon-γ signature to enrich patients who were more likely to respond to the therapy. While this biomarker seemed feasible in predicting response to durvalumab, data showed it did not correspond with a significant advantage in terms of clinical outcomes.

Geoffrey Y. Ku, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the role of durvalumab in the treatment of patients with gastric cancer.

Dr. Ku on Role of Durvalumab in Gastric Cancer

Geoffrey Y. Ku, MD, medical oncologist at Memorial Sloan Kettering Cancer Center discusses immunotherapy treatments for patients with gastric and esophageal cancers.

Researchers of a phase III study tested almost 500 patients who had previously received 2 or more chemotherapy treatments. These patients were treated with either nivolumab (Opdivo), the PD-1 antibody, or placebo.

There was a 12-month overall survival rate of 27% in these patients versus the 11% in patients who had received placebo. For the first time, this phase III evidence confirmed that these drugs are active in patients with gastric and esophageal cancers, says Ku.

Dr. Ku on Immunotherapy in Gastric and Esophageal Cancer

Geoffrey Y. Ku, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses combinations and sequencing of treatments for patients with gastric and esophageal cancers.

Patients getting the treatment in the third-line setting is too late, explains Ku. There are 10 other phase III studies that are evaluating treatment in the first- and second-line setting.

Another area of improvement is biomarker selection. Up until this point, the main biomarker has been PD-L1 expression on the tumor cells; however, it’s not perfect, Ku states. When PD-L1 is used as a biomarker, PD-L1—positive tumors respond approximately 25% of the time, whereas PD-L1–negative tumors respond 10% of the time.

Geoffrey Y. Ku, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses combinations of treatments for patients with gastric and esophageal cancers.

Geoffrey Y. Ku, MD

Articles

Dr. Ku on the Efficacy of Zanidatamab Plus Chemotherapy in HER2+ Gastroesophageal Adenocarcinoma

Dr. Ku on Evaluating Zanidatamab Plus Chemotherapy in HER2-Expressing GEA

Dr. Ku on Role of Durvalumab in Gastric Cancer

Dr. Ku on Immunotherapy in Gastric and Esophageal Cancer

Dr. Ku on Combinations and Sequencing of Treatments for Gastric Cancer