Diana L. Hanna
In this Guest Commentary, Diana L. Hanna, MD, assistant professor of clinical medicine at the University of Southern California’s Norris Comprehensive Cancer Center, discusses results of the KEYNOTE-062 study and the potential role of pembrolizumab as an alternative to chemotherapy in the frontline setting for advanced gastric or gastroesophageal junction cancer.
This year at ASCO, researchers presented results of the KEYNOTE-062 trial. This was a phase 3 trial, in which patients with PD-L1, HER2-negative, advanced gastric or gastroesophageal cancer were randomly assigned to one of three treatment arms: pembrolizumab (Keytruda, Merck) monotherapy; chemotherapy, which consisted of fluoropyrimidine plus cisplatin; or a combination of chemotherapy and pembrolizumab.
There were two parts to this study. One was to determine the noninferiority of pembrolizumab as compared with chemotherapy. The other was to determine superiority of chemotherapy plus immunotherapy compared with chemotherapy alone.
The results showed that pembrolizumab monotherapy was noninferior to chemotherapy in patients with a combined positive score (CPS) greater than 1 and especially so in patients with a CPS greater than 10. There is a marked OS difference in this subgroup of patients with a CPS greater than 10 — approximately 17 months with pembrolizumab monotherapy vs. 10 months with chemotherapy. At 2 years, almost 39% of patients were alive in the pembrolizumab arm compared with 22% in the chemotherapy arm.
These results are very exciting and have practicing-changing implications for how we treat our patients. Prior to these findings, platinum-based doublet chemotherapy or more intense chemotherapy has really been the mainstay of first-line therapy for patients with advanced gastroesophageal cancer. This opens the door to new treatment options. Still, there are a lot of questions that remain to be answered. Among them is the role of CPS. Here, the pembrolizumab benefit was primarily seen in patients with a CPS greater than 10; however, we need to find better, more precise predictive biomarkers to find the patients who would most benefit from this treatment option.
In other results, the researchers observed a higher response rate among patients in the combination arm than the chemotherapy arm. However, there was not a significant improvement in OS. This raises questions about optimal sequencing strategies and the efficacy of other chemotherapy backbones, as well as other immunotherapy agents.
In addition to looking into more predictive biomarkers, more research is needed to investigate the benefits of immunotherapy and chemoimmunotherapy in various ethnicities and regions. Finally, of course, the role and integration of HER2 directive therapies in this scheme remains to be defined.
Tabernero J, et al. Abstract LBA4007. Presented at: ASCO Annual Meeting; May 31- June 4, 2019; Chicago.
Disclosure: Hanna reports no relevant financial disclosures.