Second-line treatment of stage III/IV non-small-cell lung cancer (NSCLC) with pemetrexed in routine clinical practice: evaluation of performance status and health-related quality of life

Abstract

Background: Second-line treatment of advanced non-small-cell lung cancer (NSCLC) improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS) and health-related quality of life (HR-QoL) during second-line pemetrexed treatment in routine clinical practice.

Methods: Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation) were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI) of ≥ 10% (absolute) or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response"). HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D). Factors potentially associated with KI benefit response were evaluated using logistic regression models.

Results: Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%), 471 (90.4%) completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2%) achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%).

Conclusions: In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years), physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients.

Trial registration: Registered on ClinicalTrials.gov (NCT00540241) on October 4, 2007.

Figure 1

Shift table presenting the number of patients by baseline KI and KI after second treatment cycle with pemetrexed. KI = Karnofsky Index

Figure 2

Odds ratios for patients' characteristics potentially associated with KI benefit response after the second treatment cycle. CI = confidence interval, KI = Karnofsky Index. Odds ratios derived from univariate regression analyses, including all eligible patients (N = 521). Reference categories: KI at baseline = < 80%, prior first-line chemotherapy = single agent, time elapsed since prior chemotherapy = immediately, Grade 3/4 toxicities = none. Time elapsed since prior chemotherapy: Immediately = first dose of pemetrexed given ≤ 28 days after the last dose of first-line therapy. Within 3 months = first dose of pemetrexed given > 28 days but ≤ 3 months after the last dose of first-line therapy. Later than 3 months: first dose of pemetrexed given > 3 months after the last dose of first-line therapy

Figure 3

EQ-5D health status profiles: mean ratings for each of the 5 dimensions of the EQ- 5D questionnaire over time. On the EQ-5D questionnaire, the patient rates each of the 5 dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression) as associated with "some problems" (= 1), moderate problems (= 2), extreme problems (= 3). EQ- 5D = European Quality Of Life Five Dimensions questionnaire, QoL = Quality Of Life, n = number of patients