Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1–Expressing NSCLC

Abstract

Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m 2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/ kg compared to docetaxel (nominal two-sided p ¼ 0.03), but not for the 2-mg/kg dose.Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population.

Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non–small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial

“…Our findings are consistent with previous reports showing an improved impact on symptom burden and HRQoL for immunotherapy versus chemotherapy across first-line [22] and previously treated [8,10,23,24] NSCLC. Immunotherapies have also shown a similar trend in other tumour types [25,26].…”

<p>Feasibility and Utility of Incorporating Patient-Reported Outcomes into Surveillance Strategies for Advanced Lung Cancer</p>

“…[52][53][54] The fourth group concerned the evaluation of the role of PROs in assessing the effects of immunotherapy: the EORTC QLQ-LC13 instrument may not adequately reflect the experiences of patients who receive new therapies. 55 They concluded that commonly occurring symptoms attributed to immunotherapy can be found by using the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires. PROs disease questionnaire find some, but not all relevant symptoms in a disease area and are unlikely to discover several common toxicities related to immunotherapy drugs.…”

“…Data on PRO completion rates are available for 20 studies (60.61%) (Table 3), only in 3 studies (15%) was it lower than 80%; 44,47,59 for the others 17 (85%) it was higher than 80%. 35,36,39,40,45,48,49,51,52,[55][56][57][58]61,[66][67][68] Only in one study (5%) did the authors report a completion rate of 100%. 52 In most cases, frequencies decreased over time from baseline to subsequent measurements.…”

“…It must be emphasized that there is much evidence in the literature about the benefits of collecting and using PROs in lung cancer populations, for treatment monitoring, 35,[38][39][40][44][45][46][47][48]51,55,[57][58][59][65][66][67] detection of symptoms, 36,37,41,50,53,54,60,65 the role of patient or pathology characteristics on QoL, 40,42,56,68 to improve patientclinician communication and patient satisfaction. 43,61,62 Only one study about the effect of disease progression on QoL was identified 49 assessing the use of PROs related to efficacy outcomes (PFS, OS).…”

Immunotherapy – new perspective in lung cancer

“…The OS remained longer for immunotherapy treatment with HR = 0.53 and 0.69 for PD-L1 expression ≥ 50% and ≥1%, respectively[ 28 ]. The health-related quality of life was evaluated in keynote 010 and it was better for patients in immunotherapy group[ 29 ]. The most common AEs were hypothyroidism, hyperthyroidism, and pneumonitis.…”