In the treatment of early breast cancer, outcomes are equivalent whether paclitaxel is delivered weekly or every 2 weeks, though the weekly schedule may be better tolerated, according to the results of a phase III trial presented at the 2013 ASCO Annual Meeting.1
“The progression-free survival curves lie right on top of each other. With either schedule you get equivalent outcomes, but weekly paclitaxel is less toxic for most patients,” said G. Thomas Budd, MD, a staff physician at the Cleveland Clinic’s Taussig Cancer Institute. “The findings provide reassurance that women can choose the lower-dose weekly therapy without sacrificing their chance of survival.”
In the Southwest Oncology Group (SWOG) S0221 trial—the first to directly compare the two common taxane regimens—patients with node-positive or high-risk node-negative operable breast cancer were initially randomly assigned in a 2×2 factorial design to one of two different regimens of doxorubicin and cyclophosphamide. All patients were also randomized to one of two different regimens of paclitaxel.
In the taxane comparison, patients received paclitaxel at 80 mg/m2 weekly for 12 cycles or 175 mg/m2 every 2 weeks plus pegfilgrastim (Neulasta) for six cycles. The latter group received six cycles, not four, to achieve the same overall duration of treatment as the weekly patients, he explained.
The doxorubicin/cyclophosphamide randomization was halted for futility, and the results were presented at ASCO 2011.2 The study closed in January 2012, having accrued 3,294 patients, and at the third interim analysis, the futility boundary was crossed for the paclitaxel comparison.
At a median follow-up of 4.4 years, the estimated 5-year disease-free survival rates for weekly and every-2-week paclitaxel were equivalent—82% and 81%, respectively. There was similarly no difference in overall survival; median survival has not been reached.
“Our comparison did not show that weekly paclitaxel had superior efficacy.” Dr. Budd announced. “Since this was not conducted as a noninferiority study, we cannot make a statistical conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratio (HR = 1.05) suggest little difference in efficacy.”
In a subset analysis, patients with HER2-positive tumors tended to derive somewhat more benefit with every-2-week paclitaxel, but the hazard ratio of 1.40 was within the 95% confidence interval, he noted. “The major difference was seen in HER2-positive patients treated without trastuzumab [Herceptin] (HR = 1.71), but given the small number of patients in this subset and the lack of a biological explanation, it’s unclear whether this observation is of any significance,” he added.
Toxicity Profiles Different
There were, however, differences in toxicities between the arms. About one-third of each arm experienced some type of grade 3 or 4 toxicity. While overall and dermatologic toxicities did not differ, there was more hematologic toxicity with weekly paclitaxel, especially leukopenia (6% vs 1%, P < .001) and neutropenia (11% vs 2%, P < .001). However, patients in this arm had complete blood counts performed more often and did not receive hematopoietic growth factors routinely, he pointed out.
“Importantly, this did not result in more infectious complications, which were uncommon in both,” he noted.
In contrast, with every-2-week paclitaxel there was a higher incidence of allergic reactions (1.4% vs 0.6%, P = .035), musculoskeletal pain (11% vs 3%; P < .001), and peripheral neuropathy (17% vs 10%, P = .001). At a press briefing, Dr. Budd did acknowledge that the incidence of neuropathy is a bit lower when the every-2-week schedule is given for four cycles rather than for six, as was done in this study.
“These findings tell me that we have a choice. Either schedule can be recommended based on efficacy. We can discuss the side effects with patients and individualize treatment,” Dr. Budd concluded. “I do believe there will be a move to more weekly paclitaxel, since hematopoietic growth factors are not required.” ■
Disclosure: Dr. Budd served on an advisory board for Amgen, though not for more than 2 years. Within the past year he has served on advisory boards for and received research funding from Genentech.
1. Budd GT, Barlow WE, Moore HCF, et al: S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer. 2013 ASCO Annual Meeting. Abstract CRA1008. Presented June 3, 2013.
2. Budd GT, Barlow WE, Moore HCF, et al: First analysis of SWOG S0221: A phase III trial comparing chemotherapy schedules in high-risk early breast cancer. ASCO 2011 Annual Meeting. Abstract 1004. Presented June 6, 2011.