TY - JOUR
T1 - Impact of disease progression date determination on progression-free survival estimates in advanced lung cancer
AU - Qi, Yingwei
AU - Allen Ziegler, Katie L.
AU - Hillman, Shauna L.
AU - Redman, Mary W.
AU - Schild, Steven E.
AU - Gandara, David R.
AU - Adjei, Alex A.
AU - Mandrekars, Sumithra J.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - Background: In patients with advanced lung cancer, overall survival is largely influenced by progression status. Because progression-free survival (PFS)-based endpoints are controversial, the authors evaluated the impact of the progression date (PD) determination approach on PFS estimates. Methods: Individual patient data from 21 trials (14 North Central Cancer Treatment Group trials and 7 Southwest Oncology Group trials) were used. The reported PD (RPD) was defined as either the radiographic scan date or the clinical deterioration date. PD was determined using Method 1 (M1), the RPD; M2, 1 day after the last progression-free scan; M3, midpoint between the last progression-free scan and the RPD; and M4, an interval-censoring approach. PFS was estimated using Kaplan-Meier (M1-M3), and maximum-likelihood (M4) methods. Simulation studies were performed to understand the impact of the length of time elapsed between the last progression-free scan and the PD on time-to-progression estimates. Results: PFS estimates using the RPD were the highest, and M2 was the most conservative. M3 and M4 were similar because the majority of progressions occurred during treatment (ie, frequent disease assessments). M3 was influenced less by the length of the assessment schedules (percentage difference from the true time-to-progression, <1.5%) compared with M1 (11% to 30%) and M2 (-8% to -29%). The overall study conclusion was unaffected by the method used for randomized trials. Conclusions: The magnitude of difference in the PFS estimates was large enough to alter trial conclusions in patients with advanced lung cancer. The results indicate that standards for PD determination, the use of sensitivity analyses, and randomized trials are critical when designing trials and reporting efficacy using PFS-based endpoints. Cancer 2012.
AB - Background: In patients with advanced lung cancer, overall survival is largely influenced by progression status. Because progression-free survival (PFS)-based endpoints are controversial, the authors evaluated the impact of the progression date (PD) determination approach on PFS estimates. Methods: Individual patient data from 21 trials (14 North Central Cancer Treatment Group trials and 7 Southwest Oncology Group trials) were used. The reported PD (RPD) was defined as either the radiographic scan date or the clinical deterioration date. PD was determined using Method 1 (M1), the RPD; M2, 1 day after the last progression-free scan; M3, midpoint between the last progression-free scan and the RPD; and M4, an interval-censoring approach. PFS was estimated using Kaplan-Meier (M1-M3), and maximum-likelihood (M4) methods. Simulation studies were performed to understand the impact of the length of time elapsed between the last progression-free scan and the PD on time-to-progression estimates. Results: PFS estimates using the RPD were the highest, and M2 was the most conservative. M3 and M4 were similar because the majority of progressions occurred during treatment (ie, frequent disease assessments). M3 was influenced less by the length of the assessment schedules (percentage difference from the true time-to-progression, <1.5%) compared with M1 (11% to 30%) and M2 (-8% to -29%). The overall study conclusion was unaffected by the method used for randomized trials. Conclusions: The magnitude of difference in the PFS estimates was large enough to alter trial conclusions in patients with advanced lung cancer. The results indicate that standards for PD determination, the use of sensitivity analyses, and randomized trials are critical when designing trials and reporting efficacy using PFS-based endpoints. Cancer 2012.
KW - advanced lung cancer
KW - clinical trials
KW - disease progression date
KW - progression-free survival
KW - tumor assessment schedule
UR - http://www.scopus.com/inward/record.url?scp=84867864337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867864337&partnerID=8YFLogxK
U2 - 10.1002/cncr.27528
DO - 10.1002/cncr.27528
M3 - Article
C2 - 22434489
AN - SCOPUS:84867864337
SN - 0008-543X
VL - 118
SP - 5358
EP - 5365
JO - Cancer
JF - Cancer
IS - 21
ER -