medwireNews: The PD-1 inhibitor pembrolizumab elicits durable responses and has a manageable adverse event profile in previously treated patients with advanced gastric or gastroesophageal junction adenocarcinoma, indicates the KEYNOTE-059 trial.
These results – now published in JAMA Oncology – underlie the US FDA’s approval of pembrolizumab monotherapy for patients who have received at least two prior systemic regimens and who have programmed cell death ligand 1 (PD-L1)-positive tumors.
In the phase II trial, 259 patients with recurrent or metastatic disease – just over half (51.7%) of whom had received two prior lines of therapy, while the remainder had received three or more treatments – were given pembrolizumab 200 mg every 3 weeks until disease progression, unacceptable toxicity, or withdrawal.
Over a median follow-up of 5.8 months, 11.6% of participants achieved an objective response, with complete responses in 2.3%. Responses were achieved at a median of 2.1 months and lasted for a median 8.4 months.
The researchers, led by Charles Fuchs (Yale School of Medicine, New Haven, Connecticut, USA), report that 53.3% of responding patients were continuing to exhibit responses at data cutoff.
They add that pembrolizumab elicited responses irrespective of tumoral PD-L1 expression; however, the objective response rate (ORR) was higher among patients with tumors that were positive for PD-L1, at 15.5% versus 6.4% for those with PD-L1-negative tumors, and the median duration was also longer, at 16.3 and 6.9 months, respectively.
Responses were also observed across subgroups stratified by lines of therapy, but the ORR was higher for participants who received pembrolizumab in the third line rather than in later lines, at 16.4% versus 6.4%. The highest ORR was seen in the subgroup of PD-L1-positive patients receiving the agent as third-line therapy, at 22.7%.
“These results suggest the potential for pembrolizumab to confer sustained responses and disease control” in this patient population with “limited treatment options and poor prognosis,” say the study authors.
Treatment-related adverse events of grade 3–5 occurred in 17.8% of study participants, and led to discontinuation in two patients (bile duct stenosis and abnormal hepatic function). Two deaths, resulting from a case each of acute kidney injury and pleural effusion, were attributed to treatment by the investigators.
A total of 17.8% of patients experienced an immune-mediated adverse event of any grade, the most common being hypothyroidism, hyperthyroidism, and colitis. The incidence of grade 3 or 4 immune-mediated events was low, at 4.6%, and none resulted in death.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group