January 16, 2021 - Health-related quality of life during an 18-week period proved to be similar over for patients with esophageal cancer treated with either pembrolizumab or placebo added to chemotherapy.
Health-related quality of life (HRQoL) during an 18-week period proved to be similar over for patients with esophageal cancer treated with either pembrolizumab (Keytruda) or placebo added to chemotherapy, according to data from the phase 3 KEYNOTE-590 trial (NCT03189719) presented during the 2021 Gastrointestinal Cancers Symposium.1
Previously reported data presented at the European Society for Medical Oncology 2020 Virtual Congress demonstrated superior overall survival, progression-free survival, and overall response rates and a manageable safety profile with the pembrolizumab plus chemotherapy combination versus placebo plus chemotherapy for the treatment of patients with advanced esophageal cancer.2 The update to this trial that was presented at the 2021 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium aimed to determine if the experimental treatment had any adverse effects on HRQoL.
“The addition of pembrolizumab to chemotherapy maintained HRQoL measures relative to baseline and did not worsen HRQoL compared with chemotherapy alone,” explained lead investigator Wasat Mansoor, MBChB, MRCP, PhD, during an oral presentation. “These results support the use of pembrolizumab plus chemotherapy as first-line therapy for locally advanced and metastatic esophageal cancer or Siewert type 1 (esophagogastric junction) adenocarcinoma.”
For global health status/quality of life per the EORTC QLQ-C30 questionnaire, the least square mean (LSM) change from baseline to week 18 found no significant difference between arms (–0.10; 95% CI,–3.40 to –3.20; P = 0.9530). Further, the median time to deterioration for global health status/quality of life was similar between arms (HR, 0.86; 95% CI, 0.66-1.13; P = 0.2864).
Investigators did find that, by the QLQ-OES18 pain subscale, an LSM change from baseline to week 18 was better for the pembrolizumab and chemotherapy combination versus chemotherapy alone (–4.78 vs –1.85; [-2.94; 95% CI, –5.86 to –0.02]; P = 0.0487).
Even more, there was no significant difference found from baseline to week 18 in LSM change for both reflux (-1.19; 95% CI, –4.49 to –2.10; P = 0.4781) or dysphagia (-2.35; 95% CI, –7.78 to –3.07; P = 0.3945).
When asked about a concern for the lack of superior quality of life with the pembrolizumab plus chemotherapy combination, Mansoor explained, “We have to remember that these were secondary end points and some of them were exploratory in nature. Invariably, these trials will often show a deterioration in quality of life rather than superiority.”
The research team administered the EORTC QLQ-C30, EORTC QLQ-OES18, and EQ-5D-5L questionnaires electronically at baseline every 3 weeks up to week 24 and then every 9 weeks up to 1 year or the end of treatment. HRQoL was examined for all treated patients who completed the HRQoL assessments (n = 711).
The EORTC QLQ-C30 questionnaire was developed to assess quality of life for patients with cancer, while the EORTC QLQ-OES18 questionnaire is disease specific and was validated to address measures related to esophageal cancers. Lastly, the EQ-5D-5L model includes evaluations of mobility, self-care, usual activity, pain/discomfort, and anxiety/depression plus a visual analogue scale to measure the general state of health.
Time to deterioration in the EORTC QLQ-C30 and EORTC QLQ-OES18 questionnaires was measured as a decline from baseline of greater than or equal to 10. For all assessments, compliance at baseline and at week 18 was greater than or equal to 90%.
The primary end points of the research were overall survival and progression-free survival. Secondary end points included overall response rate and patient-reported outcomes.
Comparable safety profiles were seen with both treatment groups, and no new safety signals were detected. The mean time patients were on each respective therapy was 7.7 months for the pembrolizumab plus chemotherapy combination and 5.8 months for placebo plus chemotherapy.