Gastrointestinal Cancers Symposium
SAN FRANCISCO — The combination of S-1 plus
docetaxel failed to meet the primary endpoint of 25% improvement in OS for all
patients with advanced gastric cancer in the START study, but patients who had
non-measureable disease did see a significant improvement in OS and time to
progression on the regimen.
“The combination of S-1 and docetaxel did not meet
the primary endpoint of prolongation of OS,” said Yeul Hong Kim, MD,
PhD, with the Korea University College of Medicine in Seoul, South Korea.
“However, the use of second-line therapy was quite common in Japan and
Korea, so we think this high percentage of use of second-line or third-line or
even fourth-line therapy could impact on these results.”
Kim presented the results Thursday during the 2011
Gastrointestinal Cancers Symposium.
S-1 combined with cisplatin is a standard treatment for
advanced gastric cancer in Japan, but because that regimen requires
hospitalization, Kim and colleagues conducted START, a prospective, randomized
phase 3 trial conducted in Japan and Korea, to determine if S-1 plus docetaxel
could extend OS. The trial was designed to have 90% power to detect an
improvement in OS from 300 to 400 days.
Patients in the study arm (n=314) were assigned to 40
mg/m2 IV docetaxel on day 1 along with twice daily 40
mg/m2 S-1 for 14 days followed by 7 days rest. Patients in the
control arm (n=314) were assigned to 28 days of S-1 followed by 14 days rest.
At 2 years follow-up, Kim said median survival time was
390 days in the study group and 334 days in the control group (HR=0.88).
However, time to progression was superior in the experimental group (160 days
vs. 126) days and the difference was statistically significant (HR=0.74).
The response rate was 30.3% in the study arm and 18.4%
in the control arm.
Additionally, a subset analysis showed that in patients
with non-measurable disease, median survival time was 523 days for the S-1 plus
docetaxel group compared with 335 days for the control group (P=.0018).
Kim said time to progression was also significantly superior for the
experimental arm in this subset of patients (P=.0045).
“This study demonstrates that docetaxel plus S-1 is
an effective combination therapy for outpatient treatment of AGC and this is a
quite promising, non-platinum containing regimen for the treatment of gastric
cancer,” Kim said. – by Jason Harris
For more information:
Dr. Kim reported no relevant financial disclosures.
The statistically significant results of the SPIRITS trial make S-1 plus
cisplatin the preferred regimen for most patients in East Asia. In patients
with renal insufficiency or other contraindications to platinum, S-1 plus
docetaxel seems to be a reasonable alternative. The difference in survival
between measurable and non-measurable cohorts is interesting and merits further
investigation in future trials, particularly for docetaxel.
– Peter C. Enzinger, MD
Director, the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute