Impact of first-line and second-line PFS definitions within a randomized phase III trial in patients (pts) with metastatic pancreatic adenocarcinoma (MPA)

Abstract

e15583 Background: The FFCD phase III trial in pts with MPA comparing LV5FU2-P followed by gemcitabine (arm A) versus the opposite sequence (arm B) had failed to demonstrate a significant difference in median OS and PFS. The aim of this ancillary study was to investigate definitions of 1st and 2nd line PFS and their impacts on results. Methods: From 08/2003 to 05/2006, 202 pts with measurable MPA, PS 0–2, non prior CT were included in 33 centers, 102 in arm A and 100 in arm B. PFS1 in 1st line was defined as time interval between randomization and progression (P) or death (D) during the 1st line. Alive patients without P have been censored at the beginning of 2nd line or at the last FU. PFS2 in 2nd line was defined as time interval between randomization and P or D during the 2nd line. Alive patients without P during 2nd line have been censored at the last FU. For patients receiving only one line, PFS2 was defined as time interval between randomization and first P or D. Survival curves has been estimated using Kaplan Meier and compared using log-rank Tests. Strict ITT and modified ITT (ie pts receiving 2 lines) analyses were performed Results: Amongst the 202 pts after a median follow-up of 44 months, 69 pts (45 pts due to P) in Arm A and 55 pts (48 pts due to P) in Arm B have received a 2nd line. Median PFS was respectively equal to 3.4 months in Arm A and 3.5 months in Arm B (Stratified Log-Rank p = 0.78). For PFS1 we observed 77 and 93 events respectively in Arm A and B. Median PFS1 was equal to 4.0 months in Arm A and 3.5 months in Arm B (Stratified Log-Rank p = 0.57). For PFS2 we observed 99 and 100 events respectively in Arm A and B. Median PFS2 was equal to 5.0 months in Arm A and 5.8 months in Arm B (Stratified Log-Rank p = 0.68). Restraining PFS2 amongst patients receiving 2 lines (N = 124 pts), we observed 67 and 55 events respectively in Arm A and B, median PFS2 was equal to 6.3 months in Arm A and 8.8 months in Arm B (Stratified Log-Rank p = 0.03) Conclusions: Our results suggest that PFS2 for patients receiving 2 lines was longer when pts received Gemcitabine in 1st line. To be clinically meaningful definition of PFS1 and PFS2 should be optimized regarding censoring rules. New definitions should be proposed and assessed. No significant financial relationships to disclose.