SAN FRANCISCO—Patients treated with S-1 chemotherapy after resection for pancreatic cancer have significantly better overall survival compared with patients who received gemcitabine, researchers reported during a news conference for the Gastrointestinal Cancers Symposium (Abstract 145).
In the Phase III randomized controlled trial, two-year overall survival in S-1 treated patients was 70 percent compared with 53 percent for gemcitabine-treated patients, said the lead investigator, Katsuhiko Uesaka, MD, PhD, Medical Deputy Director at the Shizuoka Cancer Center Hospital in Japan.
“S-1 may be considered the new standard treatment for resected pancreatic cancer patients, at least in Japan,” he concluded.
When asked whether these data are likely to be transferable to the U.S. patient population, he noted that prior studies indicate that Caucasian patients have different responses to S-1 compared with Asian patients, including a substantially higher rate of diarrhea in Caucasian individuals. For example, he said, that while S-1 is approved for use in Europe for the treatment of gastric cancer, it is used at a lower dose (25 mg/m2 twice daily for three weeks, followed by one week off) relative to the dose used in the current pancreatic cancer trial (40-60 mg based on body surface twice daily for four weeks, followed by two weeks off).
“If the dose and schedule are optimized, I expect someday it will be applicable for Caucasian patients with pancreatic cancer,” Uesaka said.
‘Very Impressive, Incredibly Promising’
“The data speak for themselves,” said pancreatic cancer specialist Kenneth Yu, MD, Assistant Professor at Memorial Sloan-Kettering Cancer Center. “The results that were presented are very impressive and, I think, will lead to a lot more discussion about whether or not S-1 can be developed in the U.S. population. But certainly these are incredibly promising results.”
The trial, called JASPAC 01, enrolled a total of 385 patients who had undergone potentially curative resection for pancreatic cancer. Within 10 weeks of surgery, patients were randomly assigned to receive either gemcitabine (at 1,000 mg/m2 on days 1, 8, and 15 every four weeks for six courses) or S-1 (four six-week cycles).
The prespecified boundary for the non-inferiority trial was 1.25, with an expected hazard ratio of 0.87. Patients were enrolled between April 2007 and June 2010.
Following a preplanned interim analysis in August 2011, the data safety monitoring board recommended immediate publication of the data given the magnitude of the survival benefit. The results are statistically significant for both non-inferiority and superiority, based on a log-rank test.
There were substantial differences in adverse events between the two arms. Patients in the gemcitabine arm experienced more hematologic side effects, whereas patients in the S-1 arm had more gastrointestinal side effects.
The most common grade 3/4 non-GI adverse event was leukopenia, which occurred in about 39 percent of patients in the gemcitabine arm and about nine percent in the S-1 arm, followed by anemia (17% vs. 13%), thrombocytopenia (9% vs. 4%), elevated AST (5% vs. 1%) and elevated ALT (4% vs. 0.5%).
The most common grade 3/4 GI side effect was diarrhea (0% in the gemcitabine arm vs. about 5% in the S-1 arm) followed by stomatitis (0% vs. 3%), and vomiting (1.0% vs. 2%). Anorexia was more common in the gemcitabine arm than in the experimental arm (about 6% vs. 8.0%); fatigue was more common in the S-1 arm (4.7% vs. 5.4%).
“Pancreatic cancer remains highly lethal worldwide, but one-third of patients can undergo resection with curative intent,” said the moderator of the news conference, Neal J. Meropol, MD, Chief of the Division of Hematology and Oncology in the Department of Medicine at University Hospitals Case Medical Center and Case Western Reserve University School of Medicine. “Among these patients, we've viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone.
“For the first time we now have another option that looks superior to gemcitabine in this setting—improving the cure rate for pancreatic cancer that is resectable.”