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Dose-dense adjuvant chemotherapy reduces breast cancer mortality
SAN ANTONIO — Increasing the dose intensity of adjuvant chemotherapy reduced breast cancer recurrence and mortality, according to results of a large meta-analysis conducted by the Early Breast Cancer Clinical Trialists’ Collaborative Group and presented at the San Antonio Breast Cancer Symposium.
Researchers increased chemotherapy dose intensity by shortening the intervals between cycles, or by sequential administration instead of concurrent administration.
“We know from a lot of previous research that giving chemotherapy with an anthracycline and a taxane can reduce the chance of a woman dying of breast cancer by about a third,” Richard Gray, MSc, professor of medical statistics in the Nuffield Department of Population Health at University of Oxford in the United Kingdom, said during a press conference. “We’re still trying to figure out ways to improve how we give this chemotherapy. ... It seems that if you increase dose intensity, you might be more likely to eradicate all cancer cells.”
The current meta-analysis included three types of dose-intensification trials. These included comparisons of:
- Twice-weekly vs. standard three-times-weekly dosing, which included seven trials and 10,004 patients given the same drugs and doses, and 5,508 patients from five trials given some different chemotherapies;
- Standard sequential vs. concurrent therapy, both given three times weekly, which included 9,644 patients from five trials given the same drugs, and 1,384 patients from one trial with different drugs used; and
- Twice-weekly sequential therapy vs. three-times-weekly concurrent therapy, accounting for 6,532 patients in six trials.
“There was a whole series of studies that set out to test the hypothesis of dose intensity,” Gray said.
Recurrence and mortality served as the study’s primary endpoints.
Results of the first comparison showed the dose-dense, twice-weekly regimen significantly reduced the recurrence rate (24% vs. 28.3% RR = 0.83; 95% CI, 0.76-0.91) and 10-year breast cancer mortality rate (16.8% vs. 19.6%; RR = 0.86; 95% CI, 0.77-0.95) compared with the same chemotherapy given three times weekly.
“The reduction in mortality was almost 15%,” Gray said. “It may seem a pretty marginal difference, but we’ve already made a lot of improvements in chemotherapy and get about a third [mortality] reduction. If you can then give it dose dense, you get almost half a reduction in breast cancer mortality. These increments make a big difference to breast cancer survival.”
Results of the second comparison of sequential vs. concurrent chemotherapy showed almost a 15% reduction in recurrence (RR = 0.87; 95% CI, 0.8-0.94) and more than a 10% reduction in mortality (RR = 0.89; 95% CI, 0.8-0.99) with the sequential schedule.
“The dose intensity that you achieve with sequential is a bit less than you achieve with the two-weekly vs. three-weekly regimen,” Gray said. “This gives slightly less benefit but, clearly, the sequential [schedule] is better than concurrent chemotherapy.”
Regarding the third comparison, sequential therapy twice-weekly yielded a nearly 20% reduction in recurrence (RR = 0.82; 95% CI, 0.74-0.91) and in breast cancer mortality (RR = 0.82; 95% CI, 0.73-0.93).
“This is about twice the dose intensity compared with standard treatment,” Gray said.
Pooled analysis of all the trials showed a 15% reduction in recurrence (RR = 0.85; 95% CI, 0.81-0.89) and a 13% reduction in breast cancer mortality (RR = 0.87; 95% CI, 0.82-0.92) with the dose-dense regimens.
Safety findings suggested no increase in mortality from nonbreast cancer causes, according to Gray.
“Whichever way the trials achieved dose intensification, we saw benefits in fewer recurrences and fewer breast cancer mortalities,” Gray added. “We haven’t looked long enough at simple bread-and-butter questions, like how long to give chemotherapy for.” – by Rob Volansky
Reference:
Gray R, et al. Abstract GS1-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: The authors report no relevant financial disclosures.
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The beauty of these approaches is that we use the exact same drugs, in many cases, just with different doses. We used to give these drugs over 6 months but, with this schedule, we can give it over 4 months, which the patients prefer. The toxicity with growth factor support can be less. Everybody wins here.
We’ve been doing these approaches for the past several years because of a few pivotal trials. But, the results of those trials were not as impressive by themselves. When you look at the 10,000 or 20,000 patients included here, it shows each little trial gives little benefit. But, when you add them all together, there is great incremental benefit. Meta-analyses are not easy to do.
When you give chemotherapy the right way, you almost double the benefit. This is huge. Even in the era of immunotherapeutic drugs and other targeted drugs, the main treatment I offer my patients every single day is chemotherapy. I’d rather make it better and better tolerated.