medwireNews: Second-line pembrolizumab does not significantly improve survival compared with paclitaxel in patients with advanced gastric or gastroesophageal junction cancer positive for programmed cell death ligand 1 (PD-L1) expression, KEYNOTE-061 data show.
The phase III study included 592 patients who were randomly assigned to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel.
Of these, 196 patients in the pembrolizumab and 199 in the paclitaxel group had PD-L1-positive tumors (combined positive score [CPS] ≥1) and were followed-up for survival outcomes for a median 8.5 months.
During this time, 77% of patients in the pembrolizumab group and 88% of those in the paclitaxel group died. Median overall survival (OS) did not differ significantly between the two groups, at 9.1 and 8.3 months, respectively.
Treatment with pembrolizumab did not prolong progression-free survival (median 1.5 vs 4.1 months) or boost the response rate (16 vs 14%) relative to paclitaxel, but responses were more durable with pembrolizumab, at a median of 18.0 months, compared with 5.2 months with paclitaxel.
Although there was no survival advantage with pembrolizumab overall, subgroup analyses suggested that patients with an ECOG performance status of 0, those with a PD-L1 CPS score of at least 10, and those whose tumors had high levels of microsatellite instability might derive greater benefit from treatment with pembrolizumab than the PD-L1-positive population as a whole. Median OS times for these patients were 12.3 months, 10.4 months, and not reached, respectively.
The researchers also report that pembrolizumab had a favorable safety profile compared with paclitaxel, with fewer grade 3 or higher treatment-related adverse events reported in the former group compared with the latter (14 vs 35%).
Writing in The Lancet, Kohei Shitara (National Cancer Center Hospital East, Kashiwa, Japan) and co-investigators conclude: “The greatest relative benefit for these therapies, when given as monotherapy, might be in the setting of third-line therapy and beyond in patients with a PD-L1 combined positive score of 1 or higher (approved by the US Food and Drug Administration) and as second-line therapy in patients with good performance status or patients whose tumours show high levels of microsatellite instability or higher levels of PD-L1 expression.”
In an accompanying commentary, Elizabeth Smyth (Royal Marsden Hospital, London, UK) and Russell Petty (University of Dundee, UK) say the KEYNOTE-061 findings “reinforce the need to identify biomarkers that will maximise the benefits of anti-PD-1 therapy.”
They add: “[C]ombinatorial PD-1 blockade with chemotherapy in ongoing trials such as KEYNOTE-062 (NCT02494583) and CHECKMATE-649 (NCT02872116) or novel immuno-targeted therapies such as anti-LAG3 antibodies could provide a valuable mechanism to overcome resistance and augment the benefits of immune checkpoint blockade for most patients with gastro-oesophageal adenocarcinoma who do not respond to single-drug anti-PD-1 therapy.”
The study data were also presented at the ASCO Annual Meeting 2018 in Chicago, Illinois, USA.
By Laura Cowen
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