n SELECTED UPDA TES IN BREAST CANCER
improved overall survival, reducing the risk of death by 30% over other arms.
Toxicity was generally mild, with some differences between the regimens. The q-3-week docetaxel arm was associated with more severe neutropenia, febrile neutropenia, and infection, while weekly paclitaxel was associated with more neuropathy. The neuropathy with paclitaxel was reversible in most patients, he added.
As the discussant for this presentation, Robert Carlson, MD, Stanford University, Palo Alto, California, concluded, “Weekly paclitaxel is substantially more effective than paclitaxel given every 3 weeks, and weekly paclitaxel is more effective than either docetaxel regimen. The toxicity profile also favors weekly paclitaxel.”
Triple-Negative Breast Cancer Tumors Have Good Response to Novel Regimen
In the adjuvant treatment of breast cancer, a regimen of anthracycline plus paclitaxel (without cyclophosphamide) followed by weekly paclitaxel (AP→wP) may be as effective as the standard regimen of anthracycline/ cyclophosphamide (AC) followed by paclitaxel given every 3 weeks (AC→P). The study was reported by David Loesch, MD, of US Oncology, Houston, Texas.
“Anthracycline/paclitaxel followed by weekly paclitaxel can be considered a standard treatment in the community,” Dr. Loesch said, “although it is more neurotoxic and must be used with caution.”
In particular, this regimen was of the greatest benefit in the patients with “triple-negative” breast cancer: HER2-negative, estrogen receptor (ER)-negative, and progesterone receptor (PR)-negative, he reported. Especially in these patients, AP→wP was superior to AC →P, he reported.
The study randomized 1830 early breast cancer patients to one of these arms. About two-thirds of each arm was ER+ and/or PR+, while one-third was negative for hormone receptors. About two-thirds was also HER2-negative. Most patients had 1-3 positive lymph nodes.
In a previous interim analysis, disease-free survival at 3 years was significantly better with AP→wP: 88% vs 85% with AC→P, for a 26% reduction in relapse (p=0.05). However, the current 5-year analysis found no difference between the arms: 81% vs 80% (p=0.38), Dr. Loesch reported.
However, the differences in overall survival that were previously reported were maintained in the ASCO report. At 5 years, overall survival was 90% with AP→wP compared with 87% with AC→P, for a 24% reduction in risk with AP→wP (p=0.04; Figure 1).
Figure 1. Overall Survival (ITT).
1.0 0.9 0.8 0.7 0
p=0.04 12 24 36 Months
This 3% absolute survival difference was based on the considerable number of deaths in the AC→P arm: 106 versus 80 for AP→wP. Breast cancer deaths numbered 83 and 63, respectively.
“Omitting cyclophosphamide in the AP→wP regimen did not compromise disease-free survival or overall survival,” he pointed out.
There were no differences in disease-free or overall survival between the arm based on hormone receptor status or HER2 status. But in the unplanned analysis of triple-negative tumors, AP→wP was clearly superior. In fact, the superiority in this arm probably accounted for the difference in overall survival that was seen, according to the investigators.
Among the 378 triple-negative patients, disease-free survival at 5 years was 79% for the AP→wP arm and 74% for the AC→P arm, for a 41% reduction in risk. Overall survival was 87% and 79%, respectively. Again, this represented a 61% reduction in risk in this subgroup (p=0.037; Figure 2),
Dr. Loesch reported.
Figure 2. Overall Survival for Triple Negative ER-/PR-/ HER2neu.
1.0 0.9 0.8 0.7 0
92% 85% AC->P p=0.037 12 24 Months 36 48 60 HR=.59 79% 72 AP->wP 87% 48 90% 87% HR=.76 60 72
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