INCREASE USE OF TAXANE CHEMOTHERAPY IN BREAST CANCER

May 29, 2012 — In the treatment of breast cancer, taxane-based chemotherapy has replaced anthracycline-based chemotherapy as the preferred regimen in the United States, according to a new study.

The study, which used Medicare and private insurance claims data from 1998 to 2009, was published online May 21 in the Journal of Clinical Oncology.

The researchers found that, after 2005, there was a "sharp" increase in the use of taxane-based chemotherapy and a decline in the use of anthracycline-based chemotherapy.

In 2008, in the Medicare cohort, 51% of patients received taxane-based chemotherapy and 32% received anthracycline-based chemotherapy, report the authors, led by Sharon H. Giordano, MD, from the University of Texas M.D. Anderson Cancer Center in Houston.

"The use of anthracyclines has been quite rapidly replaced by taxane-based regimens," write the authors.

This change was seen in patients of all ages. However, patients younger than 35 years were less likely to be treated with a taxane-based regimen, "perhaps because of concerns over the higher risk of recurrence seen in younger patients," say the authors.

Also of note was the finding that women who received 21-gene recurrence score testing (Oncotype DX) were more likely to receive a taxane-based regimen. In addition, patients with HER2-positive breast cancer were more likely to receive a nonanthracycline, taxane-based chemotherapy regimen (along with trastuzumab)

"By 2008, the only identified subset of patients who were still more likely to receive anthracycline-based chemotherapy than taxane-based chemotherapy were women younger than 65 years with HER2-negative breast cancer," the authors report.

The overall change is mystifying to the authors, who speculate that the cardiotoxicity of anthracyclines is likely the major driver. However, they raise of flag of caution, saying that the "potential impact [of the change in preference] on patient outcomes is unknown" because the efficacy of taxanes are less well established.

Pivotal Studies

Dr. Giordano and colleagues believe that the pendulum swung toward taxane-based therapy because of oral presentations of 2 well-publicized studies — the US Oncology Research Trial 9735 and the Breast Cancer International Research Group (BCIRG) 006 — both of which were presented in 2005 at the San Antonio Breast Cancer Symposium.

"The 2 studies, which provided nonanthracycline chemotherapy options for both HER2-positive and HER2-negative breast cancer, may have resulted in changes in the treatment patterns of breast cancer," they write.

The US Oncology Research Trial 9735 compared docetaxel plus cyclophosphamide (TC) with a first-generation anthracycline regimen (doxorubicin plus cyclophosphamide [AC]), and reported superior overall survival in the patients treated with TC. However, this finding now has limited relevance, Dr. Giordano and colleagues suggest.

"How the TC regimen will compare with more current third-generation regimens, which incorporate both an anthracycline and taxane and are significantly more effective than AC, is still unknown, and the pivotal studies are ongoing," they write.

The BCIRG 006 trial, conducted in women with HER2-positive disease, demonstrated statistically equivalent results between AC followed by docetaxel (AC-T) plus trastuzumab and a nonanthracycline-containing regimen of docetaxel, carboplatin, and trastuzumab (TCH).

However, in both trials, toxicities might have been of keen interest, suggest the authors. In the US Oncology Research Trial 9735, the toxicities were "fairly similar" in the TC and the AC group, observe Dr. Giordano and colleagues.

The patients treated with TC had more fever and neutropenia (5.0% vs 2.5%). However, congestive heart failure developed in 1 patient treated with AC (total n = 510) and none with TC (total n = 506). Furthermore, 2 patients died while being treated with TC (1 as a result of sepsis and 1 as a result of unrelated cardiac death), and none died while being treated with AC.

"It seems surprising that this small change in toxicity profile could drive such a large change in treatment," write Dr. Giordano and coauthors.

The differences in toxicity were larger in the BCIRG 006 trial. Specifically, 21 patients developed congestive heart failure while being treated with AC-T plus trastuzumab (n = 1074), compared with 4 patients treated with TCH (total n = 1075).

In addition, 144 of the TCH patients developed distant recurrence, compared with 124 patients treated with AC-T plus trastuzumab. But these outcomes data "must be interpreted cautiously because the trial was not designed to evaluate the noninferiority of TCH compared to AC-T plus trastuzumab," say the authors.

Don't Take Too Much Stock

In a comment accompanying but not linked to the study by Dr. Giordano and colleagues, a team of breast cancer experts urge clinicians not to put too much stock in the BCIRG 006 outcomes data. In that comment, Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, and colleagues argue in favor of using anthracycline-based regimens in certain HER2-positive patients.

"Among patients at moderate to high risk of recurrence who do not have specific cardiac risk factors, the tradeoffs of efficacy and cardiotoxicity seem likely to justify the anthracycline-based treatment," they write.

Other women might be candidates for taxanes, they explain.

"For women with lower-risk HER2-positive tumors, in whom marginal differences in treatment outcome are possibly less critical, or women with clinical reasons for preferring to avoid anthracyclines, TCH is an effective and important alternative option," they write.

Dr. Giordano and her coauthors are not sure if oncologists are "abandoning" anthracyclines or if they are simply "selecting the patients they feel are most appropriate for each type of chemotherapy."

They speculate that because of "concern about cardiac toxicity, patients are requesting more taxane-based chemotherapy regimens."

The authors have disclosed no relevant financial relationships. Some of Dr. Burstein's report relationships with industry, as detailed in the paper.

J Clin Oncol. Published online May 21, 2012. Abstract, Comment