A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.
, say the researchers.
The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.
“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”
Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
S-1 widely used in Asia
S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.
“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.
The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.
The data presented at the meeting are the final results from GC-07. They confirm earlier data.
Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.
That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).
Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).
At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.
In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).
No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).
However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.
The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.
However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.
“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.
She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.
“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.
The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.
A version of this article first appeared on Medscape.com.