Discontinuation of First-Line Chemotherapy (CT) after 6 Weeks of CT in Patients (pts) with Metastatic Squamous-Cell Esophageal Cancer (MSEC): A Randomized Phase II Trial.

4002 Background: Even though there is no evidence to support the use of CT in MSEC, many physicians treat pts with good ECOG performance status (PS) with fluorouracil (5FU)/platinum-based CT. Therefore, in order to estimate overall survival (OS) in MSEC, we designed a discontinuation phase 2 trial in pts free from progression (PD) after 6 weeks (wks) of CT. Methods: PS<3 MESC pts were treated with 1st-line 5FU/platinum-based CT, and underwent tumor assessment at 6 wks. Pts free from PD after 6 wks of CT were randomized (1:1) to receive CT continuation (arm A) or CT discontinuation plus BSC (arm B). In arm B, pts were allowed to restart CT in case of PD. Primary endpoint was ITT 9-month OS rate (calculated from randomization date). The sample size has been calculated to provide an estimate of ITT 9-month OS rate ± 12.5% in arm A. Arm B served as an internal control, without formal comparison intent.With an anticipated 58% dropout rate at 1st tumor assessment, 106 pts were needed to randomize 62 pts. Secondary objectives were tolerance, PFS, quality of life, and medical costs. Results: 105 pts were included, and 101 received CT (FOLFOX: 76/101; LV5FU2-CDDPq2w: 18/101; TPF: 4/101, FU-CDDPq3w: 3/101). 67/101 pts free from PD at 6 wks were randomized. Baseline pts characteristics were as follows: median age: 64; male gender: 54/67; PS ≤1/2: 61/6; number of metastatic sites 1/≥2: 31/36; BMI<18.5kg/m²: 6/67; prior exposure to CT (combined to radiation therapy and/or surgery): 37/67. 64/67 pts were eligible and treated (arm A 31, arm B 33). CTs were LV5FU2-CDDPq2w 7/31, FOLFOX 24/31. ITT 9-months OS rate was 50% (85%-CI: 37-62) for arm A and 44% (85%-CI: 31-56) for arm B. PFS after randomization was 2.8 mo (95% CI: 1.7-5) for arm A, and 1.4 mo (95% CI: 1.4-2.7) for arm B. Tolerance was good, as expected with the CT we used. Conclusions: Inpts with MESC free from PD after 6 wks of 5FU/platinum-based CT who were randomized to the CT-continuation arm, 9-month OS rate in arm A was 50%. Despite a trend in OS and PFS favoring arm A, it does not appear that CT continuation provides much clinical benefit over CT discontinuation plus BSC, in such pts. Results of quality of life and medical costs are awaited. Clinical trial information: NCT01248299.