A phase III trial presented at ASCO showed similar efficacy between two adjuvant paclitaxel regimens, but the weekly regimen led to fewer patient side effects.
Following surgery, paclitaxel-a current standard of care adjuvant chemotherapy-is typically given one of two ways for women with breast cancer: as a higher dose every 2 weeks or as a lower dose once weekly. A randomized phase III clinical trial presented at the American Society of Clinical Oncology (ASCO) Annual Meeting showed results of the first direct comparison of the two regimens. Both dosing schedules showed similar efficacy but different toxicity profiles.
Ball-and-stick model of paclitaxel
The estimated 5-year progression-free survival for both arms were very similar-82% for the weekly regimen compared with 81% for the dose-dense biweekly regimen.
“Our results suggest that either regimen will give a good outcome, but the weekly schedule seems to result in better quality of life for patients, causing less muscle and bone pain, and allergic reactions,” said lead study author and presenter G. Thomas Budd, MD, a medical oncologist at the Cleveland Clinic in Cleveland, in a statement. “The findings provide assurance that women can choose the lower-dose therapy without sacrificing their chances of survival.”
This study suggests clinicians may be inclined to recommend the less toxic, weekly regimen to patients. The once weekly regimen may also result in lower overall cost than the biweekly regimen, due to its higher toxicity, which requires supportive care to increase white blood cell counts depleted during treatment.
“Our study applies to most patients in whom [doxorubicin] is used, as paclitaxel adds to this treatment,” Budd told Cancer Network. Alternatives for the use of paclitaxel in this patient population include docetaxel-containing regimens, including docetaxel combined with cyclophosphamide, often used in lower-risk patients, according to Budd.
The S0221 trial was led by SWOG, one of five cooperative groups within the National Cancer Institute's clinical trial network. The study enrolled 3,294 patients with node-positive and high-risk node-negative surgery-candidate breast cancer patients between 2003 and 2010. Patients were randomized to receive either paclitaxel at 80 mg/m2 once a week for 12 weeks or standard-dose paclitaxel at 175 mg/m2 every 2 weeks for 12 weeks. Patients in the standard-dose treatment arm received pegfilgrastim supportive care to increase white blood cell counts.
Differences in the toxicity profiles between the two regimens were significant, both in terms of severity and the types of toxicities experienced by patients. Five grade 5 toxicities occurred in the higher-dose treatment arm and two in the lower-dose arm. “The weekly regimen appears to be more tolerable for patients,” said Budd in a press conference.
Overall, 36% of higher-dose and 35% of lower-dose arm patients had grade 3 or 4 adverse events. More frequent allergic reactions (1.4% vs 0.6%), skin toxicities (2.7% vs 1.9%), musculoskeletal pain (11% vs 3%), and neurologic toxicities (17% vs 10%) occurred in the biweekly therapy arm compared with the weekly therapy arm, respectively. The study researchers noted that the neurologic toxicities, mainly numbness and tingling in the fingers and toes, was more pronounced in the biweekly treatment arm, compared with what is the typical biweekly regimen seen in the clinic, because patients on trial received 2 extra cycles of therapy. The extra 2 cycles of therapy was to balance the number of cycles between both study arms. Leukopenia was more frequent in the weekly dose arm (6% vs 1%) compared with the higher-dose biweekly treatment arm.
According to Dr. Budd, some patients will likely opt for the biweekly schedule, which is given for 4 rather than 6 cycles, because treatment is over with sooner. Dr. Budd does not think patients in the real-world setting will receive the 6-cycle, 12-week therapy tested in this trial.
Patients on the trial will continue to be followed to collect long-term leukemia risk and other data. Several ancillary studies are also underway or are being planned, using patient tumor samples. Those studies will explore genetic, dietary, and other lifestyle factors, such as exercise on the effect of the paclitaxel therapy.
“This study allows individualization of treatment based on side effects since the outcomes were similar,” said Dr. Budd.