Results of the KEYNOTE-062 trial suggest that pembrolizumab is noninferior to standard chemotherapy and also less toxic in patients with PD-L1-positive, HER2-negative, advanced gastric or gastroesophageal junction cancer. The results also suggested that Pembrolizumab plus chemotherapy was not superior to chemotherapy with respect to OS or progression-free survival, regardless of CPS score.
For patients with PD-L1-positive, HER2-negative, advanced gastric or gastroesophageal junction (G/GEJ) cancer, front-line treatment with pembrolizumab is noninferior to standard chemotherapy and far less toxic, according to results of the KEYNOTE-062 trial.
Additionally, pembrolizumab provided better overall survival in patients with high PD-L1 expression.
"This trial shows that front-line pembrolizumab is effective and could provide a new opportunity for people newly diagnosed with advanced gastric or gastroesophageal junction cancers," lead investigator Dr. Josep Tabernero, Head of the Medical Oncology Department at the Vall d'Hebron Barcelona Hospital University Hospital and Institute of Oncology, Barcelona, Spain, said in a statement.
Dr. Tabernero reported the study results during a press briefing June 1 at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Pembrolizumab (Keytruda, Merck) was approved in the U.S. in 2017 for recurrent, locally advanced or metastatic, G/GEJ cancer with tumors that express PD-L1 with a combined positive score (CPS) of one or more.
The phase 3 KEYNOTE-062 trial enrolled 763 patients (median age of 62); 69% had GC and 30% had GEJ cancer, all HER2-negative. About one quarter of the patients had previous tumor resection. All patients had a PD-L1 CPS of one or more, and 281 (37%) had a CPS of 10 or more.
Patients were evenly split between three groups: initial therapy with intravenous pembrolizumab alone, pembrolizumab plus standard chemotherapy, or standard chemotherapy plus placebo. Median follow up was 11.3 months (data cutoff date was March 27, 2019).
In patients with CPS of one or more, overall survival with pembrolizumab was noninferior to chemotherapy (hazard ratio = 0.91; 99.2% CI: 0.69 - 1.18). Median OS was 10.6 months with pembrolizumab and 11.1 months with chemotherapy.
For patients with CPS of 10 or more, OS was superior to chemotherapy (HR = 0.69; 95% CI: 0.49 - 0.97). Median OS was 17.4 months with pembrolizumab vs 10.8 months with chemotherapy. After two years, 39% of patients on pembrolizumab were alive compared with 22% on chemotherapy, Dr. Tabernero reported.
Pembrolizumab plus chemotherapy was not superior to chemotherapy with respect to OS or progression-free survival, regardless of CPS score.
Importantly, Dr. Tabernero told the briefing, "patients who received pembrolizumab had less adverse events and less grade 3 to 5 events and fewer patients discontinued therapy due to adverse events."
Grade 3 or higher toxic treatment-related adverse events occurred in 17% of patients on pembrolizumab, 73% of those on pembrolizumab and chemotherapy, and 69% of those on chemotherapy only. Nausea and fatigue were the most common adverse events. The safety profile of pembrolizumab was in line with prior experiences of patients treated with the drug.
G/GEJ is a "tough disease to treat and chemotherapy has been our only option for many years," ASCO Chief Medical Officer Dr. Richard L. Schilsky told the briefing. "This study, demonstrating the potential of immunotherapy to substantially improve outcomes is really important. It is quite clear that pembrolizumab is superior to chemotherapy in the high biomarker category, and pembrolizumab should replace chemotherapy - in many cases - as first-line therapy in this population."
In a phone interview with Reuters Health, Dr. Nicholas Rohs, Assistant Professor of Medicine, Hematology and Medical Oncology at The Tisch Cancer Institute at Mount Sinai in New York, called the results "exciting" and said "it's really nice to have a new option for these challenging patients."
"The results will probably change some of what I do for these advanced HER2-negative patients, where it's really been chemo or bust. This is a really difficult disease to treat and the patients really get beat up by the chemotherapy. For these higher-expressing tumors, it's great to be able to offer an immune therapy that is not inferior, and actually showed an advantage in survival while also being better tolerated," said Dr. Rohs.
The study was funded by Merck & Co. Dr. Tabernero and several colleagues have disclosed relationships with the company and other pharmaceutical companies.