S. Lindsey Davis, MD, an assistant professor of medicine and gastrointestinal medical oncologist at the University of Colorado Cancer Center, discusses an investigational immunotherapy combination being explored in patients with HER2-positive gastric and gastroesophageal junction (GEJ) cancer.

Although the phase III KEYNOTE-062 trial was negative, there are still many opportunities and new combinations for immunotherapy in the field, explains Davis. For example, data from a single-center phase II trial from Memorial Sloan Kettering Cancer Center showed that the addition of pembrolizumab (Keytruda) and trastuzumab (Herceptin) to standard frontline therapy in previously untreated patients with metastatic HER2-positive gastric/GEJ cancer resulted in high response rates and disease control.

Results from the trial showed that the combination induced a partial response rate of 87% and a disease control rate of 100% among 32 evaluable patients. Although this was a phase II trial, it is exciting, says Davis. These data have led to the phase III KEYNOTE-811 trial, in which progression-free survival and overall survival will serve as co-primary endpoints.

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Dr. Davis on Immunotherapy in HER2-Positive Gastric/GEJ Cancer

S. Lindsey Davis, MD, an assistant professor of medicine and gastrointestinal medical oncologist at the University of Colorado Cancer Center, discusses the role of ramucirumab (Cyramza) in the treatment of patients with gastric/gastroesophageal junction (GEJ) adenocarcinoma.

Data from the phase III RAINFALL trial presented at the 2018 Gastrointestinal Cancers Symposium showed that the addition of ramucirumab to standard first-line chemotherapy did not improve overall survival (OS), which served as the secondary endpoint of the study. The agent was initially FDA-approved for use in combination with paclitaxel as second-line therapy, based on data from the RAINBOW trial. Since the single agent had previously shown potent activity in heavily pretreated patients, it was thought that earlier exposure may lead to higher responses.

However, RAINFALL demonstrated that adding ramucirumab in the first-line setting does not confer an advantage in progression-free survival or OS. Accordingly, ramucirumab should only be used in the second-line setting, concludes Davis.

Dr. Davis on the Role of Ramucirumab in Gastric/GEJ Cancer

S. Lindsey Davis, MD, an assistant professor of medicine and gastrointestinal medical oncologist at the University of Colorado Cancer Center, discusses caveats of the phase III KEYNOTE-062 trial findings in gastric and gastroesophageal junction (GEJ) cancer.

Immunotherapy has garnered a lot of excitement in gastric and GEJ cancer, following the incorporation of several FDA-approved agents in the third-line setting for patients with PD-L1—positive disease. However, there have been some setbacks, explains Davis.

For example, data from the KEYNOTE-062 trial were negative. The addition of frontline pembrolizumab (Keytruda) to standard cisplatin and either 5-fluorouracil or capecitabine did not show a significant benefit in overall survival, progression-free survival, or response rate in patients with advanced gastric/GEJ cancer versus chemotherapy alone. However, there are several ongoing studies exploring immunotherapy in various lines of therapy.

Notably, investigators observed some benefit in patients who had a PD-L1 (combined positive score [CPS]) of ≥1; these patients experienced a better response with the addition of pembrolizumab to standard chemotherapy. Moreover, a subsequent analysis showed that patients with even higher scores—a CPS of 10&mdash;seemed to have even better outcomes with that type of therapy, concludes Davis.

Dr. Davis on Caveats of the KEYNOTE-062 Trial Findings in Gastric/GEJ Cancer

S. Lindsey Davis, MD, an assistant professor of medicine and gastrointestinal medical oncologist at the University of Colorado Cancer Center, discusses the potential for maintenance therapy in gastric cancer.

Aside from the many ongoing trials with immunotherapy, one study of interest is evaluating the use of a PARP inhibitor after patients have had a response to platinum-based chemotherapy in the frontline setting, says Davis. The randomized phase III, double-blind trial (NCT03427814) is examining pamiparib versus placebo as maintenance therapy and is enrolling patients with inoperable, locally advanced, or metastatic gastric cancer.

Maintenance therapy has proven to be effective in other gastrointestinal malignancies, such as colorectal cancer and pancreatic cancer, and this trial will give physicians a sense of whether the approach is worth pursuing in gastric cancer. Notably, patients are not required to have any kind of homologous recombination deficiency or DNA repair deficiency to enroll. However, these deficiencies will be evaluated in the analysis, concludes Davis.

S. Lindsey Davis, MD

Articles

Dr. Davis on Immunotherapy in HER2-Positive Gastric/GEJ Cancer

Dr. Davis on the Role of Ramucirumab in Gastric/GEJ Cancer

Dr. Davis on Caveats of the KEYNOTE-062 Trial Findings in Gastric/GEJ Cancer

Dr. Davis on the Potential for Maintenance Therapy in Gastric Cancer