S-1 Meets Docetaxel Efficacy For Previously Treated Advanced NSCLC

EAST-LC findings confirm S-1 is noninferior to docetaxel for non-small-lung cancer patients who have progressed after platinum-based chemotherapy

medwireNews: Second- or later-line treatment with the oral 5-fluorouracil-based agent S-1 matches the overall survival (OS) achieved by docetaxel chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), demonstrate findings from the East Asia S-1 Trial in Lung Cancer (EAST-LC).

Median OS was 12.75 months for the 577 patients randomly assigned to receive S-1 at a dose of 80–120 mg/day on days 1–28 of a 6-week cycle. This compared with 12.52 months for the 577 patients who were given docetaxel 60 mg/m2 or 75 mg/m2 on day 1 of a 21-day cycle.

This gave a nonsignificant hazard ratio of 0.945 and the upper limit of its 95% confidence interval was below 1.2, confirming noninferiority of S-1 to docetaxel, report Tony Mok, from the Chinese University of Hong Kong, and EAST-LC co-investigators.

The patients, who were treated at centres in China, Japan, Hong Kong, Singapore and Taiwan, also achieved similar progression-free survival with S-1 and docetaxel regimens, at 2.86 versus 2.89 months.

However, patients given S-1 achieved significantly better EORTC Quality of Life Questionnaire Core-30 scores over 48 weeks compared with the docetaxel-treated participants. S-1 was also associated with significantly better fatigue and physical, role, emotional and social functioning scores than docetaxel on the same measure.

And on a lung cancer-specific quality of life questionnaire, S-1-treated patients fared significantly better with regard to dyspnoea, peripheral neuropathy and alopecia than those given docetaxel, but had poorer quality of life in terms of dysphagia.

The authors remark in the Annals of Oncology that PD-1 pathway inhibitor therapy is the new standard of care for NSCLC who have progressed after first-line doublet chemotherapy, but that single-agent chemotherapy remains an option for patients who are ineligible or unable to afford immunotherapy.

“S-1 shares similar efficacy with docetaxel but differs in toxicity and [quality of life] profile”, Tony Mok et al conclude. “Our study confirmed S-1 as a viable treatment option for previously treated advanced NSCLC.”

The authors of an accompanying editorial note that S-1 is not commonly used in the West following report of greater gastrointestinal toxicity in European populations than in Asian patients, a pattern attributed to differences in CYP2A6 gene polymorphisms between the populations. 

“Given that diarrheagenic agents such as tyrosine kinase inhibitors of the epidermal growth factor receptor can now be safely administered with the appropriate use of loperamide, the favorable characteristics of S-1 such as oral availability and low incidence of neutropenic fever and alopecia deserve to be better appreciated in Western countries”, they suggest.

Acknowledging that the genomic heterogeneity of lung cancer means that no treatment will be uniformly effective, Hidetoshi Hayashi and Tetsuya Mitsudomi, from Kindai University in Osaka, Japan, believe that “the more weapons in the therapeutic armamentarium the better.”

“However, with the currently available biomarkers and clinical factors such as treatment line, type of driver gene mutation, as well as PD-L1 expression status and histological type of the tumor, prediction of the efficacy and toxicity of a given treatment in a given patient is not easy”, they conclude.

“It is therefore important to pursue further individualization of treatment based on the identification of new and effective biomarkers.”

References

Nokihara H, Lu S, Mok TSK, et al. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol; Advance online publication 29 September 2017. doi: https://doi.org/10.1093/annonc/mdx419

Hayashi H, Mitsudomi T. S-1 as an option for second-line treatment of NSCLC. Is the “East Side Story” applicable in the West? Ann Oncol; Advance online publication 3 October 2017. doi: https://doi.org/10.1093/annonc/mdx519