Hand-foot syndrome is a biomarker of improved survival following treatment with capecitabine

Jandu, H., Church, D., Paul, J. , Tomlinson, I., Iveson, T., Kerr, R., Kerr, D. and Palles, C. (2019) Hand-foot syndrome is a biomarker of improved survival following treatment with capecitabine. Annals of Oncology, 30(Supp4), iv117-iv118. (doi: 10.1093/annonc/mdz156.024)

Abstract

Introduction: Hand-foot syndrome (HFS) is experienced by ∼50% of patients treated with capecitabine. Trial protocols stipulate dose reductions for grade 3 events and recurrent grade 2 events and dose delays for isolated grade 2 events. Two small studies have shown improved survival of patients experiencing HFS following treatment with sorafenib or anti-VEGFR therapy (1, 2). We sought to determine the relationship between HFS and overall and disease-free survival in two randomised controlled trials (RCTs) where capecitabine was administered to stage II and stage III colorectal cancer patients. Methods: The maximum grade of HFS (CTCAE graded) experienced during treatment, overall survival and disease-free survival was available from 927 patients from the QUASAR 2 trial (3) and 526 patients from the SCOT trial (4) who had been treated with capecitabine either as a single agent or in combination with either bevacizumab or oxaliplatin. QUASAR 2 patients received 1250 mg/m2 capecitabine twice daily for 14 days and SCOT patients received 1000 mg/m2 capecitabine twice daily for 14 days. Grade 2+ HFS was experienced by 513 patients in QUASAR 2 and 78 patients in SCOT. The association between HFS and overall and disease-free survival was investigated in each study using a multivariate Cox-proportional hazards model including tumour site, stage, sex and age as covariates. Duration of treatment was included as an additional covariate in the SCOT trial where patients were randomised to receive 12 weeks or 24 weeks of treatment. Results: Mean follow-up of patients in from QUASAR 2 and SCOT was 4.48 years and 4.78 years respectively. Of the patients, 55.3% from the QUASAR 2 trial experienced ≥ grade 2 HFS and 14.82% of patients from the XELOX arm of SCOT trial experienced ≥ grade 2 HFS. QUASAR 2 patients who experienced grade 2+ HFS had an increase in overall survival compared to those who experienced no HFS or only grade 1 events (HR 0.61; 95% CI 0.45-0.83, P = .0017). A similar result was observed for disease-free survival (P = .03). HFS was far less common in the SCOT trial but data from the patients treated with capecitabine and oxaliplatin supported the findings in QUASAR 2. For overall survival, the HR was 0.74 (95%CI, 0.39-1.4; P = .36) and 0.75 (95% CI, 0.46-1.23; P = .258) for disease-free survival. In a fixed effects meta-analysis of the two trials the HR for overall survival was 0.63 (95% CI, 0.48-0.84; P = .01) and for disease-free survival 0.75 (95% CI, 0.58-0.98; P = .04). Conclusion: Dose reductions and delays as a result of HFS do not negatively impact upon survival. Data from two RCTs in the colorectal cancer setting supports HFS as a biomarker of improved survival. This finding will be explored in other studies that are part of the IDEA consortium. References: 1. Ogawa et al. Oncology. 2017;(93 Suppl 1):113-119. 2. Bailey et al. J Oncol Pharm Pract. 2018(3):190-197. 3. Kerr et al. Lancet Oncol. 2016(11):1543-1557. 4. Iveson et al. Lancet Oncol. 2018(4):562-578.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paul, Mr James
• Authors: Jandu, H., Church, D., Paul, J., Tomlinson, I., Iveson, T., Kerr, R., Kerr, D., and Palles, C.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Annals of Oncology
• Publisher: Elsevier
• ISSN: 0923-7534
• ISSN (Online): 1569-8041
• Published Online: 06 January 2020