Adjuvant S-1 ‘New Standard Care’ For Japanese Pancreatic Cancer Patients

Japanese patients with resected pancreatic cancer derive a significant overall and relapse-free survival benefit with S-1 compared with gemcitabine

medwireNews: Adjuvant chemotherapy with the oral fluoropyrimidine S-1 is superior to gemcitabine for the treatment of resected pancreatic cancer in Japanese patients, researchers report in The Lancet.

S-1 treatment nearly doubled the 5-year survival rate relative to the current standard of care gemcitabine and thus could be “a new standard care” in this patient population, say Narikazu Boku, from National Cancer Center Hospital in Tokyo, Japan, and co-workers.

However, Andrew Ko, from the University of California San Francisco in the USA, who describes the results as “eye-opening” in an accompanying commentary, points out that “[i]t is essential to recognise the possibility that interethnic variability might produce differences in both efficacy and toxicity of this drug.”

And thus, “the question of whether S-1 could be a worldwide game-changer for the adjuvant treatment of pancreatic cancer remains unresolved”, he adds.

In this phase III trial, 187 Japanese patients who had no or microscopic residual tumour after resection for stage I–III pancreatic cancer were randomly assigned to receive oral S-1 twice a day at a dose of 40 mg, 50 mg or 60 mg according to body-surface area for up to four 6-week cycles comprising 28 days on-treatment and 14 days off. Their 190 counterparts were given intravenous gemcitabine 1000 mg/m² once a week for 3 weeks followed by a 1-week rest period, for up to six cycles.

After a median follow-up of 79.3 months in the S-1 group and 82.3 months in the gemcitabine group, overall survival (OS) was a median of 46.5 and 25.5 months, respectively, giving a hazard ratio (HR) for mortality of 0.57, which was significant not only for the non-inferiority of S-1, but also for superiority.

And the 5-year OS rate in the S-1 arm was 44.1%, compared with 24.4% for gemcitabine-treated patients, a significant difference.

Indeed, Andrew Ko writes that “the observation that close to half of patients were still alive at the 5 year mark represents a result undocumented in any previous clinical trial, registry data, or institutional experience.”

Relapse-free survival (RFS) was also significantly better with S-1 than gemcitabine, with median RFS times of 22.9 versus 11.3 months (HR=0.60) and 5-year RFS rates of 33.3% versus 16.8%.

stomatitis and diarrhoea of grade 3 or 4 occurred more frequently in the S-1 group, while gemcitabine-treated participants were more likely to experience leukopenia, neutropenia and elevation of aspartate aminotransferase and alanine aminotransferase.

Significantly fewer patients discontinued the study drug in the S-1 relative to the gemcitabine group, at 28% and 42%, respectively.

“S-1 was well tolerated in the adjuvant setting”, say the study authors, but they add that S-1 needs to be assessed in non-east Asian populations as previous research has shown a higher incidence of grade 3 or 4 gastrointestinal toxicity in Western populations.

Narikazu Boku et al believe, however, that S-1 adjuvant chemotherapy could “perhaps be applicable for non-east Asian patients after careful adjustment of the dose and schedule.”

References

Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 2016; Advance online publication 2 June. doi: http://dx.doi.org/10.1016/S0140-6736(16)30583-9

Ko AH. Raising the bar for the adjuvant treatment of pancreatic cancer. Lancet 2016; Advance online publication 2 June. doi: http://dx.doi.org/10.1016/S0140-6736(16)30680-8

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