The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR-Mutant Lung Cancer
Journal
Journal of Thoracic Oncology
Journal Volume
13
Journal Issue
6
Pages
792-800
Date Issued
2018
Author(s)
Lee C.K
Lord S
Marschner I
Wu Y.L
Sequist L
Rosell R
Fukuoka M
Mitsudomi T
Asher R
Davies L
Gebski V
Gralla R
Mok T
Abstract
Introduction: Traditionally, marked tumor shrinkage has been assumed to portend better outcome. We investigated whether depth of tumor response was associated with improved survival outcomes in advanced EGFR-mutant NCLC. Methods: Individual patient data from randomized trials (EURTAC, IPASS, ENSURE, LUX-Lung 3, and LUX-Lung 6) were used. The association of depth of response with progression-free survival (PFS) and overall survival was examined using landmark analyses. Depth of response based on radiologic assessments at 6 weeks and 12 weeks was calculated as the relative changes in the sum of the longest diameters of the target lesions from baseline. Results: Of 1081 evaluable patients at 6 weeks with no disease progression, 71.2% achieved Response Evaluation Criteria in Solid Tumors response. Using a landmark analysis, EGFR-TKI was more effective than chemotherapy (PFS hazard ratio = 0.36, p <.0001); and was associated with greater mean tumor shrinkage than chemotherapy (35.1% versus 18.5%, p <.0001). However, there was no significant difference in the relative PFS benefit between treatment groups across the entire spectrum of tumor shrinkage (p =.18 for test of interaction between treatment and continuously measured depth of response). Depth of response at 6 weeks was not associated with PFS when adjusted for treatment effect (hazard ratio = 0.96, p =.78). Similar results were obtained for 12-week landmark analysis and for OS outcome. Conclusions: The PFS advantage of EGFR-TKI over chemotherapy in advanced EGFR mutant NCLC is not explained by depth of response at 6 or 12 weeks. It should not be used as a surrogate of benefit in future trials or routine clinical decision making. ? 2018 International Association for the Study of Lung Cancer
Subjects
Chemotherapy; Depth of response; EGFR mutation; Tyrosine kinase inhibitor
SDGs
Other Subjects
epidermal growth factor receptor; epidermal growth factor receptor kinase inhibitor; EGFR protein, human; epidermal growth factor receptor; protein kinase inhibitor; Article; cancer chemotherapy; comparative effectiveness; controlled study; female; human; lung cancer; major clinical study; male; overall survival; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; treatment response; tumor volume; disease free survival; enzymology; genetics; lung tumor; metabolism; mutation; pathology; prognosis; randomized controlled trial (topic); treatment outcome; Disease-Free Survival; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Mutation; Prognosis; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
Publisher
Elsevier Inc
Type
journal article