MILAN—Prolonging chemotherapy until disease progression improves progression- free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC), according to a systematic analysis conducted in Italy.
The findings address an important debate in oncology, said Alessandra Gennari, MD, of Ospedali Galliera in Genova. “In metastatic breast cancer there is substantial controversy over how long chemotherapy should be continued in the absence of significant toxicity, after the achievement of disease control,” said Gennari.
Typically, the number of cycles tends to be based on the response to treatment, symptomatic improvement, patient tolerability and, “most importantly,” physician preference, she said. “We asked whether prolonging chemotherapy after patients respond or stabilize would be associated with longer survival and time to progression.”
The investigators searched for randomized trials in the first-line MBC setting comparing longer and shorter durations of chemotherapy. Data were obtained from literature databases and meeting abstracts and through contact with individual authors of studies. Trials comparing different types of chemotherapy or including high-dose chemotherapy were excluded.
Subgroup analyses were performed according to time of randomization, type of maintenance chemotherapy, number of cycles in the shorter arm, and whether patients received concomitant endocrine treatment.
The investigators found 11 studies involving 2269 patients to be eligible for analysis.
Longer chemotherapy was better
Patients receiving chemotherapy of longer duration had a 36% reduction in the risk of progression and a 9% reduction in the risk of death. “These results are more than clinically meaningful— they are statistically significant,” Gennari said at a press briefing. “The results justify why we must tell patients that they should continue chemotherapy.”
Assuming that the median OS in MBC after first-line chemotherapy is 24 months, longer chemotherapy was associated with absolute improvements of about 3 months in PFS and 2 months in OS.
In the regression analysis, the magnitude of this effect was remarkably similar across groups of trials, and the effect of longer chemotherapy was independent of any of the factors in the subgroup analysis.
“These results provide support to the clinical approach of prolonging firstline chemotherapy in the absence of significant toxicity and disease progression,” she commented.
Questions remain as to the optimal maintenance chemotherapy, such as: Should the same drug or a different one be used? Should sequences be planned? What is the role of low-dose maintenance therapies? Would targeted agents be optimal?
“Do more prolonged side effects justify a gain of 3 months in PFS and 2 months of OS?” asked Miguel Martin, MD, of the Hospital Universitario Greg orio Marañón in Madrid, who discussed the paper at the meeting. “I guess that most patients would accept that deal.”
He said there were many caveats to the analysis, including potential literature bias. Many negative trials are never published, he noted.
“Even considering the caveats of the analysis,” he concluded, “this Italian study provides support for the administration of chemotherapy until disease progression.”