Adjuvant S-1 + docetaxel yields survival benefit for stage III gastric cancer patients following resection

A combination therapy of S-1 plus docetaxel in the adjuvant setting is not only superior to S-1 alone for recurrence-free survival (RFS) following D2 gastrectomy for stage III gastric cancer, it also confers overall survival (OS) benefit, according to the updated analysis of the JACCRO GC-07 trial presented at ASCO GICS 2021.

After a median follow-up period of 42.5 months, 67.7 percent of patients treated with S-1 plus docetaxel were still alive without disease recurrence at 3 years, compared with 57.4 percent of patients receiving S-1 alone (hazard ratio [HR], 0.715; p=0.0008). [GICS 2021, abstract 159]

This updated analysis confirmed earlier RFS benefit seen in the previous interim analysis (65.9 percent vs 49.5 percent; HR, 0.632; p=0.0007), as well as demonstrated a clear superiority of the combination therapy over S-1 alone.   

In addition, the RFS benefit with the combination therapy was observed across subgroups, with no significant interactions between treatment effect and baseline characteristics such as age, gender, pStage, histologic type, and tumour

Further, the improvements in RFS translate into survival benefit, as indicated by the significantly higher OS rate in the combination therapy arm vs the S-1 alone arm at 3 years (HR, 0.742; p=0.0076). Again, the survival advantage was seen regardless of whether it was for stage IIIA (HR, 0.0617; p=0.025), IIIB (HR, 0.881; p=0.46), or IIIC population (HR, 0.64; p=0.0032), although the difference between treatments was not significant for stage IIIB population.

“Adjuvant S-1 plus docetaxel is recommended for patients with pathologic stage III gastric cancer who underwent D2 gastrectomy without neoadjuvant chemotherapy,” said presenting author Dr Kazuhiro Yoshida from the Gifu University Graduate School of Medicine, Gifu, Japan.

Participants in the phase III study were 915 patients (mean age 66 years) with pStage III gastric cancer who had R0 resection and D2 lymphadenectomy with negative peritoneal washing cytology. Following surgery, they were randomized 1:1 to receive either S-1 + docetaxel or S-1 alone for a maximum of 1 year.

S-1 is an oral chemotherapy comprising the 5-fluorouracil (5-FU) prodrug tegafur and two biomodulators to maintain tegafur at high serum concentrations while minimizing gastrointestinal toxicity. According to the researchers, S-1 has been widely used in Asia for treating several solid tumors and presents a standard adjuvant treatment option for pathologic stage II/III gastric gastric cancer after curative resection.

Consistent with the overall RFS benefit seen with S-1 plus docetaxel, the combination therapy also led to reductions in relapse incidence at specific sites vs S-1 alone. The most prominent reductions were seen for lymphatic recurrence (incidence rate, 6.4 percent vs 15.0 percent), followed by haematogenous recurrence (9.7 percent vs 15.5 percent).

In addition, recurrence at local site (2.9 percent vs 4.4 percent) and peritoneal site (18.8 percent vs 21.4 percent) were similarly reduced with the combination therapy over S-1 alone.

“Postoperative S-1 plus docetaxel was safe and manageable. Neutropenia was the most common adverse event,” reported Yoshida, who noted that that rate of neutropenia was 39.2 percent in the combination therapy arm compared with 16.4 percent in the S-1 alone arm.

Other grade 3/4 adverse events that were more common with the combination therapy vs S-1 alone included leukopenia (22.4 percent vs 2.7 percent) and febrile neutropenia (5.7 percent vs 0.4 percent).

Calling the findings “meaningful and impactful”, invited discussant Dr Rutika Mehta of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, US said “[S-1 plus docetaxel] might find a place in the guidelines out East for stage III gastric cancer.”