Durable Remissions in Metastatic Breast Cancer With ABMT

MIAMI BEACH—Use of aggressive induction therapy followed by high-dose chemotherapy with autologous bone marrow transplantation (ABMT) yielded a 40% complete remission rate among 425 women with metastatic breast cancer treated at Duke University Medical Center. Of these women, 11% remained in complete remission 5 years after therapy, David A. Rizzieri, MD, reported at the 40th Annual Meeting of the American Society of Hematology (ASH).

Noting that the Duke results compare favorably with those of currently available standard therapies, Dr. Rizzieri characterized the ability of this intensive regimen to produce durable remissions in patients with metastatic breast cancer as a “baby step forward for high-dose therapy.”

The median age of patients participating in the study was 43 years; 306 were premenopausal; and 10% were African-Americans or another nonwhite ethnic group. More than 40% of the women (180 patients) had lung or pleural metastases, and 147 had liver involvement. More than half of the participants (250) had two or more sites of metastasis. None of the patients had received prior chemotherapy for metastatic disease.

Thus, the women were fairly representative of metastatic breast cancer patients and not a highly select group, Dr. Rizzieri told Oncology News International in an interview.

Treatment Regimen

The participants first received 2 to 4 cycles of the Duke AFM regimen—fluorouracil (750 mg/m²/d infused continuously for 5 days), doxorubicin (250 mg/m² on days 3 through 5), and methotrexate (250 mg/m² for 10 minutes on day 15, with leucovorin rescue if necessary).

Patients who responded completely to AFM were randomized to immediate high-dose therapy plus ABMT or were followed very closely (every 6 weeks) and given high-dose therapy at the first sign of relapse. Women who had only a partial response to the induction regimen underwent immediate high-dose therapy, while those whose disease did not respond or progressed were taken off study and followed for survival.

The preparative regimen used in this study was STAMP 1, consisting of cyclophosphamide (1,875 mg/m² on days -6 through -4), cisplatin (55 mg/m² via continuous infusion on days -6 through -4), and carmustine (600 mg/m² delivered at a rate of 5 mg/m²/min on day -3).

Overall, 315 (74%) of the 425 women responded to AFM, 113 with a complete response and 202 with a partial response. Of the 315 patients who responded to induction therapy, 299 (100 complete and 199 partial responders) actually received high-dose therapy plus ABMT.

At the end of the entire treatment regimen, 40% of patients (171/425) were in complete remission. Of the 299 patients who underwent high-dose therapy, 58% (171/299) attained a complete remission. This complete remission rate, Dr. Rizzieri told ONI, is higher than that achieved with standard chemotherapy, although not significantly so.

He added, “We were able to convert one-third of patients who had a partial response to induction therapy to actual complete response with high-dose therapy,” characterizing this as a “significant” conversion rate.

CRs Maintained Over the Long Term

Even more important, Dr. Rizzieri said, was that women whose disease responded completely to the intensive regimen stayed in remission over the long term. Of all 425 patients enrolled in the study, 11% remained in complete remission at 5 years. Among the subgroup of patients who responded to AFM and received ABMT, 16% were alive and still completely free of disease at the 5-year mark (for an overall survival rate of 20%). The smaller subgroup of patients who had a complete response to AFM and remained in remission after high-dose therapy enjoyed a 20% progression-free survival rate at 5 years and a 38% overall survival rate.

When asked whether the Duke group uncovered any characteristics that could be used to identify patients who maintained remission over the long term. Dr. Rizzieri said that women with liver metastases appeared to have a worse outcome than did those with nonvisceral sites of metastasis. However, he said, “these are patients with liver metastases who remain in long-term remission.” Other factors predictive of a poor prognosis, he said, were the failure of prior adjuvant therapy and a short duration of first complete response.

Dr. Rizzieri noted that there were no statistically significant differences between women randomized to immediate vs delayed transplant. Thus, it would not be “unreasonable” for a patient with newly diagnosed metastatic breast cancer to receive standard chemotherapy and, if a remission is obtained, be monitored closely for signs of relapse, and then given high-dose therapy if such signs were observed.

However, given that most patients will relapse eventually, Dr. Rizzieri believes that high-dose therapy has a better chance for success if started when the patient is in remission rather than after relapse, as new protocols are focusing on manipulation of minimal residual disease post-transplant.