Lung cancer symptom scale outcomes in relation to standard efficacy measures - An analysis of the phase III study of pemetrexed versus docetaxel in advanced non-small cell lung cancer

Background: Patients with advanced non-small cell lung cancer (NSCLC) require care that emphasizes symptom palliation in addition to extending survival. The low response rates and minimal survival gains observed in second-line studies underscore the need to assess treatment efficacy with symptomatic end points. Methods: To characterize the relationship between patient-reported health-related quality of life outcomes and efficacy end points (tumor response, overall survival [OS], progression-free survival [PFS]), retrospective analyses were performed on Lung Cancer Symptom Scale (LCSS) data (n = 488) from the phase III study of pemetrexed (500 mg/m(2) once every 3 weeks) versus docetaxel (75 mg/m(2) once every 3 weeks) in advanced NSCLC. The LCSS data consisted of patient ratings of six symptoms and three summary items using 100-mm visual analogue scales. The mean maximum improvement for each item was categorized according to best tumor response, with statistical analyses based on a two-factor interaction model (with treatment arm and response group as fixed factors). Additional analyses pooled data between treatment arms and examined correlation (nonparametric and Pearson's) of time to first worsening of symptoms (TWS) with PFS and OS. Results: All LCSS items, except hemoptysis, showed mean maximum improvement over baseline for responders and patients with stable disease (p < 0.01), with greater improvement associated with response. Median TWS for each LCSS item ranged between 2.3 months (fatigue) and 7.0 months (cough), with correlation between TWS and PFS and OS (all p values <= 0.017). Conclusions: For most NSCLC patients, second-line chemotherapy provides symptomatic improvement that is linked to standard efficacy outcomes. Health-related quality of life data provides complementary efficacy information that can guide routine clinical practice.