ESMO 2014 Abstract 1266P: Quality of life results from the phase 3 REVEL randomised clinical trial of ramucirumab+docetaxel versus placebo+docetaxel in second-line advanced/metastatic NSCLC patients with progression after platinum-based chemotherapy.
Edward B. Garon et al.
Background: Ramucirumab is a recombinant human monoclonal antibody that specifically binds to the extracellular domain of vascular endothelial growth factor receptor 2 with high affinity. Results from the global phase 3 REVEL study comparing the addition of ramucirumab to docetaxel in the second-line treatment of advanced NSCLC demonstrated a median PFS of 4.5 months for the combination arm compared to 3.0 months for the docetaxel alone arm (p<0.0001) with a corresponding increase in median OS to 10.5 months vs. 9.1 months (HR 0.86, CI 0.75-0.98; p=0.023). This study aimed to determine the effect of this regimen on quality of life (QoL).
Methods: The authors measured the Lung Cancer Symptom Scale (LCSS), a patient-reported assessment that includes 6 items focused on lung cancer symptoms (appetite loss, fatigue, cough, dyspnea, hemoptysis and pain) plus 3 global items (symptom distress, difficulties with daily activities and global QoL) as well as the ECOG performance status at baseline, every cycle and at the end of therapy. In addition, the Average Symptom Burden Index (ASBI) was calculated as the mean of the 6 symptom items and the LCSS total score was calculated as the mean of all 9 items.
Results: Patient compliance with the questionnaires was approximately 75% and equal in both arms of the study. While there was a general increase in symptom burden over time as measured by the LCSS and ASBI, there was no difference identified in the magnitude of change in either group and it appeared to occur at a similar rate. Stratified hazard ratios for the time to deterioration for total LCSS total score was HR=0.99 (0.81-1.22; p=0.932) and for ASBI it was HR=0.93 (0.75-1.15; p=0.514) with approximately 70% of patients censored.
CARE Faculty Perspective: QoL is an important element to consider when managing patients with advanced lung cancer particularly in the second-line setting as they often have a heavy burden of symptoms. Even though there was no improvement in QoL with the addition of ramucirumab, it is encouraging to see that the benefits gained in OS were not at the expense of a detriment in QoL or patient functioning. However, there was no discussion regarding the use of concomitant supportive care medications or access to palliative care personnel nor how these may have affected the results. In addition, it is unknown what affect on the outcome may be attributed to the high level of patient censoring. Although targeting the VEGF-receptor pathway in NSCLC appears to have clinical activity, the benefit is modest and it remains to be seen whether this strategy will gain popularity in a tumour site where VEGF inhibitors did not.
Rob El-Maraghi, MD