728P - Randomized phase II trial of S-1 versus S-1 plus oxaliplatin (SOX) in patients with gemcitabine refractory pancreatic cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anticancer agents
Pancreatic Cancer
Therapy
Biological Therapy
Presenter Takuji Okusaka
Authors T. Okusaka1, S. Ohkawa2, H. Isayama3, A. Fukutomi4, K. Yamaguchi5, M. Ikeda6, A. Funakoshi7, M. Nagase8, S. Nakamori9, Y. Hamamoto10
  • 1Division Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 2Department Of Gastroenterology, Kanagawa Cancer Center Hospital, Kanagawa/JP
  • 3Department Of Gastroenterology, Graduate School of Medicine The University of Tokyo, Tokyo/JP
  • 4Division Of Gastrointestinal, Shizuoka Cancer Center, Shizuoka/JP
  • 5Division Of Gastroenterology, Saitama Cancer Center, Saitama/JP
  • 6Division Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital East, Chiba/JP
  • 7Department Of Gastroenterology, National Kyushu Cancer Center, Fukuoka/JP
  • 8Department Of Medical Oncology, Jichi Medical University Hospital, Tochigi/JP
  • 9Department Of Surgery, Osaka National Hospital, Osaka/JP
  • 10Tochigi, Department Of Clinical Oncology, Tochigi Cancer Center, Tochigi/JP

Abstract

Background

Gemcitabine (Gem) monotherapy or Gem-based combination therapy is used as standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. The addition of oxaliplatin (L-OHP) to 5-FU/LV, however, yielded a significant improvement in overall survival (OS) and progression-free survival (PFS) in a second-line setting in the CONKO 003 trial. As S-1, an oral fluoropyrimidine derivative, is commonly used to treat advanced PC rather than 5-FU/LV in Japan, we conducted a randomized phase II trial to evaluate the efficacy and safety of S-1 plus L-OHP (SOX) compared with S-1 alone in a second-line setting.

Material and methods

The inclusion criteria were as follows: 1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; 2) confirmed PD after Gem treatment; 3) ECOG PS, 0-1; 4) measurable metastatic lesion based on RECIST criteria; 5) age ≥ 20 years. Patients were randomized to receive either S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm A) or SOX (L-OHP 100 mg/m2, iv, d1 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q3w; Arm B). The primary endpoint was PFS to detect the superiority of Arm B over Arm A.

Results

Of a total of 271 pts enrolled between January 2009 and July 2010, 264 were eligible (130 randomized to Arm A and 134 to Arm B). Median PFS in Arm A and B was 2.8 and 3.0 months, respectively (HR= 0.838; 95% CI, 0.649-1.082; P = 0.1795) with a median follow-up time of 12.6 months. Median OS in Arm A and B was 7.0 and 7.5 months, respectively (HR = 1.031; 95% CI, 0.791-1.344; P = 0.8235) with a median follow-up time of 13.8 months. Response rate (RR) was 11.5% in Arm A (15/130; 95% CI, 6.6-18.3) and 20.9% in Arm B (28/134; 95% CI, 14.4-28.8)(P = 0.0395). The incidences of grade 3/4 toxicities were as follows: neutropenia (11.4% and 14.0%), thrombocytopenia (3.8% and 9.8%), anorexia (11.4% and 12.5%), diarrhea (4.5% and 5.1%) and nausea (3.0% and 9.8%) in Arm A and B, respectively. Both regimens were tolerable.

Conclusions

Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Disclosure

T. Okusaka: The study detailed in the abstract was funded by a pharmaceutical company.

S. Ohkawa: The study detailed in the abstract was funded by a pharmaceutical company.

H. Isayama: The study detailed in the abstract was funded by a pharmaceutical company.

A. Fukutomi: The study detailed in the abstract was funded by a pharmaceutical company.

K. Yamaguchi: The study detailed in the abstract was funded by a pharmaceutical company.

M. Ikeda: The study detailed in the abstract was funded by a pharmaceutical company.

A. Funakoshi: The study detailed in the abstract was funded by a pharmaceutical company.

M. Nagase: The study detailed in the abstract was funded by a pharmaceutical company.

S. Nakamori: The study detailed in the abstract was funded by a pharmaceutical company.

Y. Hamamoto: The study detailed in the abstract was funded by a pharmaceutical company.