Dynamic change of fatigue of pemetrexed maintenance treatment in the JMEN trial

Li Zhang; Chandra P Belani; Ping-Hai Zhang; Xin Wang; Lulu Yang; Mauro Orlando; Yi-Long Wu

doi:10.1016/j.lungcan.2017.11.026

Dynamic change of fatigue of pemetrexed maintenance treatment in the JMEN trial

Lung Cancer. 2018 Jan:115:121-126. doi: 10.1016/j.lungcan.2017.11.026. Epub 2017 Nov 28.

Authors

Li Zhang¹, Chandra P Belani², Ping-Hai Zhang³, Xin Wang⁴, Lulu Yang³, Mauro Orlando⁵, Yi-Long Wu⁶

Affiliations

¹ Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China.
² Penn State Milton S. Hershey Medical Center, Penn State Hershey Cancer Institute, Hershey, PA, USA.
³ Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, PR China.
⁴ Asia Pacific Statistical Sciences, Lilly China Drug Development and Medical Affairs Center, Shanghai, PR China.
⁵ Oncology Emerging Markets, Eli Lilly Interamérica Inc., Buenos Aires, Argentina.
⁶ Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, PR China. Electronic address: [email protected].

PMID: 29290253
DOI: 10.1016/j.lungcan.2017.11.026

Abstract

Objectives: In the JMEN trial, patients with advanced non-squamous non-small cell lung cancer (NSCLC) without progression after platinum-based first-line therapy derived extended survival, delayed disease progression, and maintained overall quality of life (QoL) from pemetrexed maintenance therapy. However, fatigue was the most common physician-reported non-hematological toxicity in the pemetrexed group. This post hoc analysis investigated dynamic change of fatigue.

Materials and methods: Analysis of the overall safety population with squamous and non-squamous NSCLC subgroups included Common Terminology Criteria for Adverse Events to summarize adverse event (AE) rates by cycle and AE investigator-reported severity. Worsening of fatigue, defined as +15mm or more from baseline on a 100mm scale, evaluated QoL using the patient-reported Lung Cancer Symptom Scale. Patients with worsening fatigue and time-to-worsening of fatigue symptoms were also analyzed.

Results: Drug-related fatigue occurred more frequently with pemetrexed than placebo. The drug-related grade 3/4 fatigue was also higher in the overall population on pemetrexed than with placebo. Fatigue incidence during pemetrexed maintenance after induction was not altered with cumulative exposure. Percentage of patients who experienced worsening of fatigue based on patient-reported LCSS scores was comparable between the two arms in cycles 1-10. The time-to-worsening of fatigue was similar between the pemetrexed arm and the placebo arm in the overall population; however, the East Asian subpopulation patients taking pemetrexed experienced a longer median time-to-worsening of fatigue than patients taking placebo.

Conclusion: Analyses suggest that despite higher incidence of any grade drug-related fatigue compared with placebo in patients with advanced NSCLC, pemetrexed maintenance does not impair patient-reported QoL.

Keywords: East asian; Fatigue; Non-squamous non-small cell lung cancer; Pemetrexed; Quality of life (QoL).

Publication types

Clinical Study
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use*
Asian People*
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / epidemiology
Carcinoma, Non-Small-Cell Lung / mortality
Disease Progression
Drug-Related Side Effects and Adverse Reactions / epidemiology*
Fatigue / epidemiology*
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / epidemiology
Lung Neoplasms / mortality
Pemetrexed / adverse effects
Pemetrexed / therapeutic use*
Quality of Life
Surveys and Questionnaires
Survival Analysis

Substances

Antineoplastic Agents
Pemetrexed