news from Istanbul--are all taxanes created equal?

[Lani]

Taxane Regimens for First-Line Therapy of Breast Cancer

Zosia Chustecka
October 2, 2006 (Istanbul) — Three taxane regimes were equally effective as first-line therapy in advanced breast cancer and offer an alternative to the anthracyclines, a group of Greek researchers reported here at the 31st Congress of the European Society for Medical Oncology (ESMO).

"Anthracyclines are the backbone of therapy for advanced breast cancer, but they carry the risk of potentially life-threatening cardiotoxicity," commented one of the study investigators, Helena Linardou, MD, from the Metropolitan Hospital in Athens, Greece. "The cardiotoxicity observed with anthracyclines is potentially fatal," she continued, and includes congestive heart failure, which can significantly impair a patient's quality of life and incur substantial healthcare costs. The risk of cardiotoxicity increases exponentially with cumulative doses, and this limits the repeated use of these drugs. This class includes daunorubicin, doxorubicin, epirubicin, and idarubicin.

"The use of an effective alternative that lacks such risks is very attractive," Dr. Linardou said at an ESMO press conference. Previous studies have shown that the use of taxanes, with the addition of trastuzumab in HER2-positive patients, is one of the most effective and better-tolerated regimens.

In their study, the Hellenic Cooperative Oncology Group, headed by George Fountzilas, MD, set out to compare 3 taxane regimens as first-line therapy in women with advanced breast cancer. A total of 414 patients were randomized as follows:

Group A received 6 cycles of paclitaxel 175 mg/m2 over 3 hours, followed by carboplatin at an area under the curve (AUC) of 6 every 3 weeks.
Group B received gemcitabine 100 mg/m2 over 30 minutes on days 1 and 8, followed by docetaxel 75 mg/m2 on day 8.
Group C received paclitaxel 90 mg/m2 over 1 hour weekly for 12 weeks.

In addition, letrozole was given to all hormonal-sensitive patients until progression, along with ovarian ablation exclusively to premenopausal women. Also, in an addition to the protocol after the trial was already under way, patients with HER2-overexpressing tumors received trastuzumab.

The results showed no significant difference in survival between the 3 groups. At a median follow-up of 22 months, survival was 33 months in group A, 27 months in group B, and 41 months in group C. There were also no significant differences in the secondary end points of median time to progression (11, 11, and 12 months, respectively) or in the overall response rate (38%, 46%, and 49%, respectively). The 3 regimens were similar in costs (€15,260, €15,400, and €15,915, respectively).

Asked whether she was surprised that all 3 regimens were so similar, Dr. Linardou said that previous studies suggested that paclitaxel used alone may be superior, and in this study there was a nonsignificant trend favoring paclitaxel alone. Follow-up is still ongoing, and a final analysis will be completed in December.

Differences in Toxicities, Tailoring to Patients

All 3 regimens were associated with a significant improvement in quality of life over time. This was measured on the EuroQoL EQ50 questionnaire, which covers mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It was completed before chemotherapy, on completion of chemotherapy, and 6 months later.

Although all 3 regimens were well tolerated, there were significant differences in several toxicities. Severe myelotoxicity was significantly higher in group B, reported by 31% of patients, compared with 13% in group A and 10% in group C (P < .001), while severe peripheral neuropathy was seen, as was expected, only in the arms that included paclitaxel (5% in group A, 0% in group B, and 8% in group C; P = .008).

"All 3 regimens are active and well tolerated, show a significant improvement in quality of life, and cost the same," Dr. Linardou commented. Hence, all 3 can be used and the choice of treatment tailored to the patient, she concluded. In presenting the results at the meeting, Dr. Fountzilas said that treatment could be personalized to meet the requirements of the patients.

Discussant for this paper and chair of the session, Martine Piccart, MD, from the Jules Bordet Institute, in Brussels, Belgium, agreed with this statement. The take-home message is that there is no new standard of care and that the optimal single agent looks as good as combinations, she said. As the 3 regimens had similar quality of life and costs, and assuming equivalent efficacy on average, patient preference can dictate the choice of treatment. For example, from the point of view of visits to the hospital, as well as the incidence of grade 3 alopecia, the paclitaxel/carboplatin combination is the worst, while the gemcitabine/docetaxel combination is the worst for grade 3 mucositis but the best for neurotoxicity.

However, Dr. Piccart also criticized the study. It was powered for an unrealistic 20% difference in survival between the groups (hazard ratio, 1.79), which is a "really huge difference," she said. To look for a more realistic difference of 10% (HR, 1.30), the study is underpowered, and this will not change even with longer follow-up. Also, the results were possibly confounded by the addition of trastuzumab, which was used in about one third of patients. Finally, she criticized the study for being conducted only in Greece in the current era of widespread international collaborations. Dr. Piccart herself has led by example in such collaborations, having spearheaded the Breast International Group, which now comprises 39 groups across 21 countries.

ESMO 31st Congress: Abstract 1430. Presented October 1, 2006.