Novel drug shows potential for advanced colon cancer
TAS-102, a novel antitumor drug for patients with inoperable, metastatic colorectal cancer, improved survival time, reduced risk of death and achieved better overall disease control compared with placebo, according to results of a phase 2 study.
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide and accounts for about 10% of all cancer cases. There are currently no treatment options for patients with advanced, inoperable colon cancer who do not respond to standard treatment, according to background information in the study.
In the multicenter, double-blind, randomized trial, Takayuki Yoshino, MD, of the department of gastroenterology and gastrointestinal oncology at National Cancer Center Hospital East in Chiba, Japan, and colleagues evaluated 169 patients aged 20 years or older with advanced colon cancer and a treatment history of two or more regimens of standard chemotherapy.
Researchers randomly assigned patients to either TAS-102 (n=112) or placebo (n= 57) group.
Patients assigned to TAS-102 (Taiho Pharmaceuticals) received 35 mg/m² orally twice a day in a 28-day cycle.
Median follow-up was 11.3 months.
Median OS in the TAS-102 group was 9 months (95% CI, 7.3-11.3) compared with 6.6 months (95% CI, 4.9-8.0) in the placebo group (HR for death=0.56; P=.0011).
An independent review showed 49 patients (43%) assigned to TAS-102 achieved disease control compared with six (11%) assigned to placebo (P<0.0001).
“The increase in disease control in the TAS-102 group could have contributed to the improved PFS and OS in patients treated with this agent,” Yoshino and colleagues wrote.
Serious adverse effects occurred in 21 patients (19%) in the TAS-102 group compared with five (9%) in the placebo group. No treatment-related deaths occurred.
Half of the patients assigned to the study drug developed grade-3/grade-4 neutropenia, 28% developed leucopenia and 17% developed anemia.
In the placebo group, no patients had grade-3 or higher neutropenia or leucopenia. Three patients (5%) had grade-3 or higher anemia.
“TAS-102 has promising efficacy with a manageable safety profile in patients with metastatic colorectal cancer who are refractory or intolerant to standard chemotherapy,” Yoshino and colleagues concluded.
An international phase 3 study evaluating and confirming the clinical benefits of TAS-102 is under way.
In an accompanying editorial, Alberto Sobrero, MD, head of the oncology unit for the Ospedale San Martino in Genoa, Italy, called the study results “strong” and “impressive.” He urged caution, however, noting that the results must be confirmed in a phase 3 trial.
“With the assumption that the results represent the true effect of TAS-102, a new important advance in the treatment of colorectal cancer will have been made,” Sobrero wrote.
Disclosure: The researchers report consulting fees, honoraria and research funding from Bristol-Myers Squibb, MerckSerono, Takeda, Bayer, Novartis and AstraZeneca, as well as advisory board and speaker roles with Roche, Merck, Amgen, Bayer and Nordic.