TAS-102 significantly improved overall survival in patients (pts) with refractory metastatic colorectal cancer (mCRC). The most common treatment-related adverse event of TAS-102 is bone marrow suppression, such as neutropenia. Potential predictive value of neutropenia caused by cytotoxic drugs has been reported in various types of cancer.
We retrospectively analyzed 86 consecutive refractory mCRC pts who received TAS-102 at two Japanese institutions between May 2014 and March 2015. To evaluate the association between survival and neutropenia, pts were divided into four categories according to the grade of neutropenia during the first course (4 weeks) of TAS-102: Category A (grade 0-1, n = 48), B (grade 2–4, n = 38), C (grade 0-2, n = 65), and D (grade 3-4, n = 21).
Pts characteristics were as follows: median age 64 years old (range 32–90); male 59%; PS 0-1 90%; primary site colon 56%; KRAS exon2 wild 58%; number of metastatic site ≥3 55%. With a median follow up time of 7.6 months (m) (range 3.8- 12.6), median progression free survival (mPFS) was 2.1 m, disease control rate (DCR) was 36.3%, and median overall survival (mOS) was 5.7 m. The association between neutropenia and efficacy is shown in the table below. Multivariate analysis in both Category A vs B and C vs D showed that neutropenia was the only significant predictive factor of DCR and mPFS.
The association between neutropenia and efficacy of TAS-102
|Category A vs B||Category C vs D|
|DCR||%||25.0 vs 50.0||29.5 vs 57.9|
|OR, p value||2.96, 0.03||3.23, 0.03|
|mPFS||m||1.8 vs 2.9||1.9 vs 4.8|
|HR, p value||0.50, 0.003||0.40, 0.002|
|mOS||m||4.4 vs 6.4||5.3 vs 6.7|
|HR, p value||0.66, 0.11||0.49, 0.04|
Neutropenia during the first course caused by TAS-102 was associated with better efficacy. Neutropenia may be a surrogate marker for adequate antitumor doses of TAS-102.
Clinical trial identification
S. Hamauchi, K. Yamazaki, H. Taniguchi: lecture fees from Taiho Pharmaceutical. All other authors have declared no conflicts of interest.