Disease-free survival (DFS) was not enhanced in patients with early-stage, triple-negative breast cancer (TNBC) treated with additional capecitabine (Xeloda, Genentech, Roche) compared with observation alone in patients who had previously received standard, adjuvant chemotherapy, new research indicates.
On the other hand, statistically significant improvements in both DFS and overall survival (OS) were seen in patients who received additional capecitabine compared with observation alone if they had a nonbasal phenotype of TNBC.
“We were disappointed to find that adding adjuvant capecitabine to standard treatment did not significantly improve disease-free or overall survival,” Miguel Martin, MD, PhD, professor of medicine, Universidad Complutense, Madrid, Spain, said in a statement.
“However, given that we found a subset of patients with nonbasal-like disease seemed to have a significant benefit from capecitabine…we strongly recommend that patients with triple-negative breast cancer discuss adjuvant capecitabine with their oncologists,” he added.
The study was presented during a press briefing here at the San Antonio Breast Cancer Symposium (SABCS) 2018.
The CIBOMA/2004-01_GEICAM/2003-11 study was a phase III trial in which investigators assessed the potential benefit of administering adjuvant capecitabine after patients had been treated with six to eight cycles of chemotherapy consisting of an anthracycline plus a taxane, or treated with anthracycline alone.
Patients with node-negative disease received four cycles of doxorubicin plus cyclophosphamide.
A total of 448 patients received eight cycles of additional capecitabine, at a dose of 1000 mg/m2 twice a day, on days 1 through to 14, every 3 weeks, while 428 others received no further adjuvant treatment and were randomized to the observational group.
Approximately two thirds of the cohort overall were postmenopausal, and approximately 60% had stage II disease at diagnosis.
Some 80% of both groups received adjuvant chemotherapy alone while approximately two thirds received anthracycline plus a taxane-based adjuvant regimen.
At a median follow-up of 7.3 years, DFS rates were 79.2% for patients who received additional capecitabine and 76.8% for observational controls for a nonsignificant adjusted hazard ratio (HR) of 0.79, as Martin reported.
Similarly, OS rates were not significantly different between the two groups, with 86.2% of patients in the capecitabine arm still alive at follow-up compared with 85.9% of observational controls for an HR of 0.92, he added.
Subgroup Analysis
On the other hand, among 248 patients with a nonbasal phenotype defined by immunohistochemistry, differences in both DFS and OS at the same follow-up point were significantly different between the 2 groups.
For example, DFS rates were 82.6% in the capecitabine group vs 72.9% for those randomized in the observation alone arm (HR, 0.53; P = .02).
Similarly, 89.5% of those patients were alive at follow-up if they received capecitabine compared with 79.6% for those who received observation alone (HR, 0.42; P = .007).
Grade 3 or higher hand-foot syndrome was the most common adverse event associated with capecitabine, which occurred in about 20% of extended adjuvant group.
“Tolerance of extended adjuvant capecitabine was as expected,” Martin observed. “And my personal opinion is that capecitabine is useful for some TNBC patients.”
Investigators are now pursuing genomic studies to better understand why the nonbasal-like group responded so differently to capecitabine than patients with ductal TNBC.
“If we could identify this population of patients — those who actually benefit from capecitabine — that would be great for patients,” Martin observed.
The problem now is that a diagnosis of TNBC is where the diagnosis stops.
Press briefing moderator and SABCS codirector, Carlos Arteaga, MD, said a distinction is not made between patients with the basal and the nonbasal phenotype of TNBC, but rather they are all lumped together under the umbrella diagnosis of TNBC.
Arteaga is from the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas.
“This makes the distinction between the two [phenotypes] very challenging,” Arteaga said.
“So an important message from this study is that patients with TNBC are a very heterogeneous group and we need to start better educating ourselves about this [heterogeneity] and define these phenotypes better,” Dr. Arteaga emphasized.
The study was sponsored by CIBOMA and supported by Roche, who provided capecitabine.
Martin declares he has received speaker honoraria from Pfizer and Lilly and has participated in advisory boards and received honoraria from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly. He also declares he has received research grants from Novartis and Roche. Arteaga has disclosed no relevant financial relationships.
SABCS 2018: Abstract GS2-04. Presented December 5, 2018.
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