In a study reported in the Journal of Clinical Oncology, Adenis et al found that health-related quality of life was maintained with both pembrolizumab and chemotherapy in the pivotal phase III KEYNOTE-181 trial, which included patients with advanced esophageal cancer who had received previous treatment.
The study supported the July 2019 approval of pembrolizumab for the treatment of patients with recurrent, locally advanced, or metastatic esophageal squamous cell carcinoma whose tumors have a PD-L1 combined positive score (CPS) of ≥ 10 and who had experienced disease progression after one or more prior lines of systemic therapy.
Study Details
In the trial, 628 patients with squamous cell carcinoma or adenocarcinoma were randomly assigned to receive pembrolizumab or investigator’s choice of chemotherapy with paclitaxel, docetaxel, or irinotecan. Pembrolizumab prolonged overall survival in patients with PD-L1 CPS ≥ 10. The current prespecified analysis assessed health-related quality of life among patients with squamous cell carcinoma (n = 387), as well as among patients with a CPS of ≥ 10 (n = 218), and among patients with squamous cell carcinoma and a CPS of ≥ 10 (n = 166). Health-related quality of life was assessed with the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC questionnaire (OES18), and EuroQol 5-dimension questionnaire (EQ-5D).
Key Findings
Among the 387 patients with squamous cell carcinoma, decreases in global health status/quality-of-life mean scores between baseline and week 9 were smaller in the pembrolizumab group (least squares mean [LSM] difference = 2.80, 95% confidence interval [CI] = -1.48 to 7.08) than in the chemotherapy group (LSM difference = -6.01, 95% CI = -9.24 to -2.79). The between-group difference was not clinically meaningful (LSM difference = 2.80, 95% CI= -1.48 to 7.08), with clinically meaningful difference defined as change from baseline of ≥ 10 points.
Patients with squamous cell carcinoma in both treatment groups exhibited stable functioning and symptom scores on the QLQ-C30 and QLQ-OES18 from baseline to week 9.
For the squamous cell carcinoma pembrolizumab vs chemotherapy groups, hazard ratios for time to deterioration (first onset of deterioration of ≥ 10 points from baseline) were 1.22 (95% CI = 0.79–1.89) for pain, 2.38 (95% CI = 1.33–4.25) for reflux, and 1.53 (95% CI = 1.02–2.31) for dysphagia.
Findings in the CPS ≥ 10 and squamous cell carcinoma with CPS ≥ 10 subgroups were generally similar to those in the squamous cell carcinoma subgroup. For example, in the CPS ≥ 10 subgroup, changes in global health status/quality-of-life least squares mean score from baseline to week 9 were -3.30 (95% CI = -7.55 to 0.96) with pembrolizumab and -6.97 (95% CI = -11.45 to -2.50) with chemotherapy, with a least squares mean difference between groups of 3.68 (95% CI = -2.28 to 9.64). In the squamous cell carcinoma with CPS ≥ 10 subgroup, changes were -3.84 (95% CI = -8.39 to 0.70) with pembrolizumab and -10.40 (95% CI = -15.41 to -5.38) with chemotherapy, with a between-group difference of 6.55 (95% CI = 0.01–13.10).
The investigators concluded, “In patients with advanced esophageal cancer, pembrolizumab monotherapy and chemotherapy maintained health-related quality of life in patients with squamous cell carcinoma, CPS ≥ 10, and [squamous cell carcinoma and] CPS ≥ 10.”
Antoine Adenis, MD, PhD, of the Institut du Cancer de Montpellier and IRCM Université Montpellier, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
