Pembrolizumab Did Not Improve PFS or OS Compared With Paclitaxel in Relapsed Gastric or Gastroesophageal Junction Cancer
Results from the KEYNOTE-061 were presented at ESMO World GI 2018.
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Pembrolizumab did not improve progression-free survival (PFS) or overall survival (OS) compared with paclitaxel in patients with previously treated gastric or gastroesophageal junction (GEJ) cancer, according to data from the KEYNOTE-061 trial (ClinicalTrials.gov Identifier: NCT02370498) presented at the ESMO World Congress on Gastrointestinal Cancer 2018.1
Results from the KEYNOTE-012 and -059 trials (ClinicalTrials.gov Identifers: NCT01848834 and NCT02335411, respectively) suggested that pembrolizumab had antitumor activity against relapsed/refractory gastric or GEJ cancer. The purpose of this trial was to evaluate the efficacy and safety of pembrolizumab in this population in a phase 3 trial.
The international, open-label, phase 3 KEYNOTE-061 trial randomly assigned 395 patients with advanced gastric or GEJ adenocarcinoma to receive pembrolizumab or paclitaxel. All patients had previously progressed after first-line treatment with platinum and fluoropyrimidine chemotherapy. The co-primary endpoints were OS and PFS in patients with a PD-L1 combined positive score (CPS) greater than or equal to 1.
The objective response rate was 15.8% with pembrolizumab and 13.6% with paclitaxel. Median PFS was also similar between groups at 1.5 and 4.1 months with pembrolizumab or paclitaxel, respectively (HR, 1.27; 95% CI, 1.03-1.57).
There was no significant difference in overall survival, with a median of 9.1 months (95% CI, 6.2-10.7 months) with pembrolizumab compared with 8.3 months (95% CI, 7.6-9.0 months) with paclitaxel (hazard ratio [HR], 0.82; 95% CI, 0.66-1.03) after a median of 8 months of follow-up. The 12- and 18-month OS rates were higher with pembrolizumab at 39.8% and 25.7%, respectively, compared with 27.1% and 14.8%, respectively, with paclitaxel. A post hoc analysis indicated that patients with a CPS greater than or equal to 10 demonstrated a prolonged median OS of 10.4 months with pembrolizumab compared with 8.0 months with paclitaxel (HR < 0.64; 95% CI, 0.41-1.02) and in tumors that had high microsatellite instability, regardless of CPS with a median OS not reached with pembrolizumab compared with 8.1 months with paclitaxel (HR, 0.42; 95% CI, 0.13-1.31).
The duration of response was longer with pembrolizumab at 18.0 months compared with 5.2 months with paclitaxel.
Grade 3 to 5 drug-related adverse events occurred in 34.8% of patients who received paclitaxel compared with 14.3% of patients who receive pembrolizumab. Discontinuation rates due to adverse events were 5.4% and 3.1% with paclitaxel and pembrolizumab, respectively.
The authors noted that “pembrolizumab had a better safety profile than paclitaxel,” and though this study did not show an improved OS with pembrolizumab, other trials of pembrolizumab monotherapy in gastric and GEJ cancers are ongoing.
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- Shitara K, Özgüroğlu M, Bang YJ, et al. KEYNOTE-061: Phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer. Ann Oncol. 2018;29 (suppl 5;abstr LBA-005):v123. doi: 10.1093/annonc/mdy208.004