Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial
Mené dans 23 pays sur 307 patients atteints d'un cancer colorectal présentant une haute instabilité des microsatellites ou une déficience MMR, cet essai de phase III compare l'intérêt, du point de vue de la qualité de vie, du pembrolizumab et d'une chimiothérapie de première ligne
Background : In the KEYNOTE-177 study, pembrolizumab monotherapy provided statistically significantand clinically meaningful improvements in progression-free survival versus chemotherapyas first-line treatment in patients with microsatellite instability-high or mismatchrepair-deficient metastatic colorectal cancer. To further support the efficacy andsafety findings of the KEYNOTE-177 study, results of the health-related quality oflife (HRQOL) analyses are reported here. Methods : KEYNOTE-177 is an open-label, randomised, phase 3 trial being done at 192 cancer centres in 23 countries, in patients aged 18 years and older with microsatellite instability-highor mismatch repair-deficient metastatic colorectal cancer, with an Eastern CooperativeOncology Group performance status of 0 or 1, and who had not received previous systemictherapy for metastatic disease. Eligible patients were randomly assigned (1:1) centrallyby use of interactive voice response or integrated web response technology to receivepembrolizumab 200 mg intravenously every 3 weeks or investigator's choice chemotherapy(mFOLFOX6 [leucovorin, fluorouracil, and oxaliplatin] or FOLFIRI [leucovorin, fluorouracil,and irinotecan] intravenously every 2 weeks with or without intravenous bevacizumabor cetuximab). Patients and investigators were not masked to treatment assignment.The primary endpoints were progression-free survival (previously reported) and overallsurvival (data to be reported at the time of the final analysis). HRQOL outcomes wereevaluated as prespecified exploratory endpoints. The analysis population comprisedall randomly assigned patients who received at least one dose of study treatment andcompleted at least one HRQOL assessment. HRQOL outcomes were mean change from baselineto prespecified week 18 in European Organisation for Research and Treatment of CancerQuality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Colorectal29 (EORTC QLQ-CR29) scale and item scores, and in the EuroQoL 5 Dimensions 3 Levels(EQ-5D-3L) visual analogue scale and health utility scores; the proportion of patientswith improved, stable, or deteriorated scores from baseline to prespecified week 18in EORTC QLQ-C30 scales and items; and time to deterioration in EORTC QLQ-C30 globalhealth status/quality of life (GHS/QOL), physical functioning, social functioning,and fatigue scores and EORTC QLQ-CR29 urinary incontinence scores. The threshold fora small and clinically meaningful mean difference in EORTC QLQ-C30 score was 5–8 points.This study is registered with ClinicalTrials.gov, NCT02563002 and is ongoing; recruitment is closed. Findings : Between Feb 11, 2016, and Feb 19, 2018, 307 patients were enrolled and randomly assigned to receive pembrolizumab (n=153) or chemotherapy (n=154). The HRQOL analysis population comprised 294 patients (152 receiving pembrolizumab and 142 receiving chemotherapy).As of Feb 19, 2020, median time from randomisation to data cutoff was 32·4 months(IQR 27·7–37·8). Least squares mean (LSM) change from baseline to prespecified week18 showed a clinically meaningful improvement in EORTC QLQ-C30 GHS/QOL scores withpembrolizumab versus chemotherapy (between-group LSM difference 8·96 [95% CI 4·24–13·69];two-sided nominal p=0·0002). Median time to deterioration was longer with pembrolizumabversus chemotherapy for GHS/QOL (hazard ratio 0·61 [95% CI 0·38–0·98]; one-sided nominalp=0·019), physical functioning (0·50 [95% CI 0·32–0·81]; one-sided nominal p=0·0016),social functioning (0·53 [95% CI 0·32–0·87]; one-sided nominal p=0·0050), and fatiguescores (0·48 [95% CI 0·33–0·69]; one-sided nominal p<0·0001). Interpretation : Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL comparedwith chemotherapy in patients with previously untreated microsatellite instability-highor mismatch repair-deficient metastatic colorectal cancer. These data, along withthe previously reported clinical benefits, support pembrolizumab as a first-line treatmentoption for this population.
The Lancet Oncology 2021