Dr. John N. Primrose presents Abstract 4006.
The BILCAP randomized study (Abstract 4006) examined a cancer type for which “outcomes are poor—the 1- and 5-year survival rates are 22% and 9%, respectively,” Dr. Primrose said.
He explained that “right now, the only curative treatment is surgical resection,” but only 15% to 20% of patients are eligible. Of those, there is a 15% 5-year survival rate.
In the two-arm, open-label, controlled study, patients were randomly assigned after surgery to observation or to capecitabine (1,250 mg/m2) twice daily for eight cycles; the primary outcome was OS (by the intent-to-treat [ITT] population). Secondary outcomes were relapse-free survival (RFS), toxicity, quality of life, and health economics (the latter of which was not presented). The researchers determined that 410 enrolled patients were needed to detect a hazard ratio (HR) of 0.69—ideally, to increase the 2-year OS from approximately 60% to 71%.
Between 2006 and 2014, 224 patients were randomly assigned to observation, and 223 were randomly assigned to capecitabine to form the ITT population. The per-protocol analysis included 220 patients in the observation group and 210 in the capecitabine group. Patients were well matched at baseline; 122 patients (55%) in the capecitabine ITT group received all eight cycles, and 10 patients (< 5%) received no cycles.
In the ITT population, the median OS in the capecitabine group was 51.1 months (95% CI [34.6, 59.1]) and 36.4 months in the observation group (95% CI [29.7, 44.5]). The 15-month difference was not statistically significant (HR 0.81, 95% CI [0.63, 1.04]; p = 0.097).
However, when analyzed by the per-protocol population, the difference became significant (HR 0.75, 95% CI [0.58, 0.97]; p = 0.028). The median OS was 52.7 months in the capecitabine group (95% CI [40.3, not reported]) and was 36.1 months in the observation group (95% CI [29.6, 44.2]).
The RFS times were also statistically significant in favor of capecitabine in the ITT group (24.6 vs. 17.6 months; HR 0.76, 95% CI [0.58, 0.99]; p = 0.039) and the per-protocol group (25.9 vs. 17.6 months; HR 0.71, 95% CI [0.54, 0.92]; p = 0.011).
“The effect does seem higher in [men],” Dr. Primrose said about the interesting trends, but no real differences were noted in tumor site. “Quality of life is undiminished by the use of capecitabine,” he said, adding that capecitabine “should be the control arm in future adjuvant trials in patients with biliary tract cancers.”
Dr. E. Gabriela Chiorean discusses Abstract 4006.
Biliary tract cancers are “extremely heterogeneous,” she noted, and the widely varying median OS can range from 8 to 79 months in gall bladder cancer and is around 36 months in perihilar cancers, she said.
The National Comprehensive Cancer Network guidelines “are all over the place,” Dr. Chiorean said, mainly because of the lack of phase III trials and “a paucity of well-controlled data” during the past decade.
“The 15-month improvement seen in the BILCAP study is highly relevant even if not statistically significant,” she said. Ongoing adjuvant trials include gemcitabine/cisplatin compared with observation (ACTICCA-1), the results of which are expected in 2022, and the Chinese study of gemcitabine/oxaliplatin (GEMOX) compared with capecitabine, with results due in 2018.
For now, though, “adjuvant capecitabine improves OS in biliary tract cancers,” Dr. Chiorean said, and should be the new standard of care.
–Michelle Dalton, ELS