Breast cancer patients can obtain the same disease control but with less toxicity when they receive weekly low-dose chemotherapy compared to a dose-dense regimen every two weeks, according to a large US study that could prove practice changing in breast cancer management.
The Southwest Oncology Group (SWOG) S0221 trial compared two commonly used schedules of paclitaxel as adjuvant therapy for breast cancer in order to determine whether one schedule leads to better results than the other.
Presenting the results at ASCO 2013 in Chicago, lead author Dr George Thomas Budd, a staff physician at the Cleveland Clinic in Ohio, reported that both schedules were equally effective in women with high-risk stage I to III breast cancer: Five-year progression-free survival (PFS) rates were practically the same for paclitaxel administered weekly (82%) and paclitaxel administered every two weeks (81%).
Although no difference was seen in overall toxicity between the two arms, with more than a third of patients having some type of grade 3 or 4 toxicity during treatment, the toxicity profiles had significant differences. The low-dose weekly schedule was far less toxic than the dose-dense biweekly schedule in terms of neurologic events (17% versus 10%), musculoskeletal pain (11% versus 3%) and allergy (1.4% versus 0.6%)
Dr Budd pointed out that the S0221 trial was comparing six cycles of dose-dense versus weekly, whereas common practice is to give only four cycles. He explained that six cycles in the biweekly regimen was chosen so that patients in both groups would be on treatment for 12 weeks.
He also suggested that the weekly schedule could cost significantly less than the biweekly dose-dense option, in which patients received routine haematopoietic growth factor support.
“Either regimen can be selected on the basis of efficacy,” Dr Budd said. “So, in practice, treatment can be selected based on other considerations, such as toxicity.”
Responding to a question from the floor concerning cost savings, he said that no formal pharmaco-economic analysis has been performed, however, a ‘back of the envelope calculation’ does show that the weekly schedule involves lesser drug costs by reducing the need for growth factor support.
“For me, this is actually going to change my practice,” Dr Andrew Seidman, a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, told an ASCO press briefing. “These data suggest to me that I can get the same benefit with less toxicity, possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial.”
He also remarked that, for patients whose livelihoods depend on their fine motor skills, the issue of reduced neuropathy with the weekly schedule would be particularly relevant.
Tamoxifen: long term benefits
Meanwhile, updated results from the aTTom trial found that women with early-stage breast cancer, who received an extended duration of adjuvant tamoxifen therapy from five to 10 years had a reduced risk of recurrence and breast cancer mortality.
Prof Richard Gray, professor of medical statistics at the University of Oxford, UK, told an ASCO plenary session that 10 years of tamoxifen was associated with a significant 15% reduction in the risk of recurrence, compared with five years of tamoxifen, and a major 25% reduction in the risk of breast cancer mortality starting at year 10.
Almost 7,000 women were enrolled in the aTTom trial, results of which align closely with those from the recently published ATLAS trial. Prof Gray said this was “proof beyond reasonable doubt” that continuing tamoxifen beyond five years reduces the risk of late recurrence and reduces breast cancer mortality.
In fact, the benefit of tamoxifen in the aTTom trial may be even greater than reported, as 60% of enrolled patients had an unknown estrogen receptor (ER) status. An estimated 15% of patients likely had ER-negative disease and did not benefit from tamoxifen. He noted that extending the duration of tamoxifen had little effect on non–breast cancer mortality.
Although there was an increased risk of endometrial cancer with the use of extended tamoxifen, Prof Gray remarked that the absolute hazard was low at 0.5%. Otherwise, there were no safety concerns with the extended use of tamoxifen as reported.
Increase in pathologic complete response
Adding carboplatin to a regimen of neoadjuvant therapy resulted in a significant increase in pathologic complete response (pCR) for patients with breast cancer, Dr Gunter von Minckwitz of the German Breast Group reported to an ASCO breast cancer oral abstract session.
He revealed that an increase of more than 20% in pCR was seen in women with triple-negative breast cancer, but no benefit was seen in those with HER2+ breast cancer in the GeparSixto trial.
This randomised phase II study compared the results of neoadjuvant chemotherapy with and without the addition of carboplatin in 595 patients with centrally confirmed triple-negative breast cancer or HER2+ breast cancer. Dr von Minckwitz said that discontinuation of all treatments because of an adverse event occurred in 37.7% of the arm receiving carboplatin and 31.5% of the arm not receiving carboplatin.
Dr Judy Garber, director of the Center for Cancer Genetics and Prevention at the Dana-Farber Cancer Institute in Boston, coimmented on the high number of adverse events in the trial.
“One wonders what modifications might have made this regimen more tolerable for women in all arms of the study,” she said, adding that it remains to be determined in whom the platinum agents are effective, and whether and at what disease stage carboplatin can be added to the routine care of patients with triple-negative breast cancer.
Dr George Thomas Budd, staff physician, Cleveland Clinic, Ohio, US. Photo by © ASCO/Scott Morgan 2013 (click to enlarge)
