2019 ASCO: KEYNOTE-062: Pembrolizumab With or Without Chemotherapy vs Chemotherapy in Advanced Gastric or GEJ Adenocarcinoma
The randomized, phase III KEYNOTE-062 trial achieved its primary endpoint, showing that for patients with programmed cell death ligand 1 (PD-L1)-positive, HER2-negative, advanced gastric or gastroesophageal junction (GEJ) cancer, initial therapy with pembrolizumab resulted in noninferior overall survival compared with standard chemotherapy. Additionally, pembrolizumab showed clinically meaningful improvement in overall survival among patients with tumors that had high levels of PD-L1 expression. At 2 years, 39% of patients who received pembrolizumab alone were alive, compared with 22% of people who received standard chemotherapy. The trial also evaluated combined treatment with pembrolizumab and standard chemotherapy, and it found this regimen did not improve survival relative to chemotherapy alone. These results were presented by Tabernero et al at the 2019 ASCO Annual Meeting (Abstract LBA4007).
“This trial shows that front-line pembrolizumab is effective and could provide a new opportunity for people newly diagnosed with advanced gastric or GEJ cancers,” said lead study author Josep Tabernero, MD, PhD, Head of the Medical Oncology Department at the Vall d’Hebron Barcelona Hospital University Hospital and Institute of Oncology. “There remains a significant unmet need for treatments for these cancers and our results reinforce the importance of continued research in this field.”
Pembrolizumab was given accelerated approval by the U.S. Food and Drug Administration in September 2017 for patients with recurrent locally advanced or metastatic gastric or GEJ cancer with tumors that express PD-L1 with a combined positive score (CPS) of 1 or more.
Study Methods
The trial enrolled 763 patients with a median age of 62; 26% had previous gastric surgery to remove a tumor. In total, 69% had gastric cancer and 30% had GEJ cancer. Investigators focused on HER2-negative cancers alone, which studies have shown have a higher chance of recurrence after treatment, to limit factors that could affect outcomes.
PD-L1 expression was assessed via CPS. Previous studies of gastric or GEJ cancers have demonstrated that patients with a PD-L1 CPS of 1 or more may benefit from pembrolizumab, whereas a PD-L1 CPS of 10 or more indicates a higher likelihood of benefit. In the current trial, all patients had a PD-L1 CPS of at least 1, and 281 (37% of the enrollees) had a PD-L1 CPS score of 10 or more.
The investigators randomly assigned patients, in equal numbers, to receive one of three treatment options as initial therapy: intravenous pembrolizumab; pembrolizumab and chemotherapy; or chemotherapy plus placebo. The patients were followed for a median of 11.3 months.
Key Findings
The trial reached its primary endpoint, demonstrating that overall survival for pembrolizumab was noninferior to standard chemotherapy. A favorable survival outcome was seen among enrolled patients with a PD-L1 CPS of 10 or more. Specific findings include:
- Patients with a PD-L1 CPS of 1 or more: Survival was noninferior to chemotherapy (hazard ratio [HR] = 0.91); the median overall survival was 10.6 months for those receiving pembrolizumab compared with 11.1 months for those who received chemotherapy.
- Patients with a PD-L1 CPS 10 or more: Survival with pembrolizumab was superior to chemotherapy (HR = 0.69); the median overall survival was 17.4 months for those receiving pembrolizumab compared with 10.8 months for those receiving chemotherapy. After 2 years, 39% of people taking pembrolizumab were alive compared with 22% of those taking chemotherapy.
Overall survival and progression-free survival for the combination treatment of pembrolizumab and chemotherapy were comparable with those of chemotherapy alone, regardless of CPS.
The rates of serious side effects were lowest among patients treated with pembrolizumab alone. Grade 3 or higher toxic treatment-related adverse events were found in 17% of people receiving pembrolizumab, 73% of people receiving pembrolizumab and chemotherapy, and 69% of those receiving chemotherapy alone. The most common adverse events were nausea and fatigue.
Next Steps
The investigators are currently analyzing subsets of data to determine who benefited the most. Dr. Tabernero noted that better biomarkers than PD-L1 are needed to determine who the best responders might be to pembrolizumab alone or with chemotherapy.
The trial enrolled 58% of patients from North America, Europe, and Australia; 25% from Asia; and 17% from other regions of the world. The researchers are currently analyzing the effectiveness of the medicines based on prespecified geographic regions.
Disclosure: This study received funding from Merck & Co., Inc. For full disclosures of the study authors, visit coi.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
