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Maintenance therapy improved PFS, increased toxicity in metastatic breast cancer
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CHICAGO — Women with metastatic breast cancer assigned ongoing maintenance therapy with a gemcitabine plus paclitaxel regimen had longer PFS but increased toxicity compared with women assigned observation therapy.
“The duration of chemotherapy in this disease remains controversial,” said study researcher Young-Hyuck Im, MD, of Sungkyunkwan University School of Medicine in Seoul, South Korea.
The primary purpose of the prospective, randomized, multicenter, phase 3 study was to determine whether maintenance chemotherapy with gemcitabine plus paclitaxel is superior to observation regarding PFS in patients who responded after six cycles of first-line gemcitabine plus paclitaxel therapy. The chemotherapy regimen administered was gemcitabine 1,250 mg/m2 on day 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 3 weeks. The median number of cycles administered in the maintenance group was 12 (range 6-32).
Of 324 patients enrolled initially, 231 met response criteria. There were 116 patients assigned maintenance chemotherapy and 115 assigned observation. There were 172 patients with hormone receptor–positive disease.
The median follow-up duration was 33 months.
Maintenance therapy was linked to a superior median PFS than observation (12 vs. 8.3 months; P=.03). “The PFS from randomization was 7.5 months in the maintenance arm and 3.8 months in the observation arm, with a hazard ratio of 0.73,” Im said.
More benefit regarding PFS was observed in patients aged younger than 50 years (adjusted HR=0.5; P=.001) and those with hormone receptor–negative disease (HR=0.52, P=.019).
Median OS was 36.8 months in the maintenance arm and 28 months in the observation arm (P=.047).
The rate of at least grade-2 neurotoxicity was 41.7% in the maintenance arm and 33.3% in the observation arm, which was a nonstatistically significant difference.
“Toxicities were more common in the maintenance arm, as expected,” Im said.
No significant differences were observed regarding quality of life.
Eligible participants had metastatic breast cancer and were enrolled between 2007 and 2010 from 10 centers in Korea. “Eligibility criteria included histologically confirmed metastatic or recurrent breast cancer,” Im said. “Patients were pre- or postmenopausal and had measurable or nonmeasurable lesions.”
Im concluded that maintenance therapy substantially prolonged PFS from randomization. “OS was significantly prolonged in the maintenance group, and toxicities were well-tolerated and manageable,” he said. “No impairment in the quality of life was observed in the maintenance arm. Maintenance therapy after six cycles of therapy in metastatic breast cancer should be considered in patients with [hormone receptor]–negative tumors, visceral disease, high tumor burden, young age and postmenopausal patients.”
For more information:
Im YH. #1003. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: Dr. Im reports no relevant financial disclosures.
Perspective
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Kathy D. Miller, MD
The study was designed to test these two strategies of maintenance and observation. Here we see that a longer duration of therapy was linked to substantially longer PFS and minimal but perhaps statistically significant OS, but at the cost of increased toxicity. These results suggest that there is an increase in nearly all toxicities but no trade-off in quality of life.
There were a few devilish details with the analysis of this study. The primary endpoint was not a Kaplan-Meier based PFS. We are essentially looking at a response rate for PFS, which allowed the study to be done with slightly less statistical rigor and a smaller number of patients. They used one-sided testing quite reasonably since there was only one outcome that was of interest, but with a less rigorous HR. They reported adjusted HRs without telling us what the unadjusted HRs were, or what factors went into those adjustments. Finally, the quality-of-life analysis, while reassuring, does not tell us about some of the missing data.
But their overall results are consistent with what we’ve seen in other studies, which is that longer duration of therapy results in superior tumor control at the cost of increased or ongoing toxicity.
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