ASCOUpdated results of a phase III trial show that the addition
of the anti-HER2/neu monoclonal antibody (MoAb) Herceptin
(trastuzumab) to chemotherapy improves survival in patients with
metastatic breast cancer, compared with chemotherapy alone.
Herceptin plus either AC (Adriamycin and cyclophosphamide) or
paclitaxel (Taxol) reduced the relative risk of death by about
one-quarter and extended median survival time by the same amount,
Larry Norton, md, said at ASCO.
Dr. Norton, chief of medical oncology and director of the Lauder
Breast Center at Memorial Sloan-Kettering Cancer Center, said that
this result is particularly noteworthy given that about two-thirds of
patients randomized to chemotherapy alone subsequently received
Herceptin when their disease progressed.
The 469 patients with HER2-overex-pressing metastatic breast cancer
enrolled in the trial were divided into two strata. Patients who had
not received prior adjuvant chemotherapy (n = 281) were randomized to
doxorubicin (or epirubicin) and cyclophosphamide with or without
Herceptin, whereas those who had been previously exposed to adjuvant
chemotherapy (n = 188) were randomized to paclitaxel with or without
Preliminary results of the trial had shown significant improvements
in time to progression, response rate and duration, and 1-year
survival in patients treated with combination therapy, albeit at the
cost of increased cardiotoxicity. The updated results, obtained after
a median follow-up of 29 months, showed that Herceptin combined with
either chemotherapy regimen decreased the relative risk of death by
24% and increased median survival time from 20.3 to 25.4 months.
This Changes Everything
With these results, Herceptin joins a very short list of agents
that have proven, in a randomized trial, to improve overall survival
for metastatic breast cancer, George Sledge, Jr., MD, of
Indiana University, said in his discussion of the trial. He noted
that this changes everything. Testing for HER2 and use of
Herceptin in HER2-positive patients should be considered part of
standard care for patients with metastatic breast cancer, he said.
Nevertheless, further study is warranted to address many unresolved
issues surrounding the use of Herceptin in breast cancer. One of the
most important of these, according to both Dr. Sledge and Dr. Norton,
is integration of the MoAb into the adjuvant setting.
Further study also is needed, Dr. Norton said, to compare Herceptin
plus weekly paclitaxel with Herceptin plus the more traditional,
every-3-week schedule of the taxane.
A Phase II Trial
Weekly paclitaxel plus Herceptin showed favorable results in another
trial presented at ASCO. In this phase II cooperative study conducted
at Memorial Sloan-Kettering and M.D. Anderson, Herceptin plus weekly
paclitaxel showed activity in patients with metastatic breast cancer
with toxicity similar to that seen in previous studies of paclitaxel alone.
As reported by Monica Fornier, MD, of Sloan-Kettering, only 1 of the
63 patients with HER2-positive or HER2-negative metastatic breast
cancer treated with weekly paclitaxel and Herceptin suffered a
cardiac event. This individual had previously received a cumulative
doxorubicin dose of 615 mg/m².
Overall, left ventricular ejection fraction and cardiac
function were preserved throughout the 10 months of treatment,
Dr. Fornier noted. Peripheral neuropathy was the most common
toxicity, but was mostly moderate in severity, and febrile
neutropenia was infrequent.
Herceptin plus weekly paclitaxel produced responses in 62% of
patients with HER2-positive disease and 44% of those with
HER2-negative cancers, for an overall response rate of 52%.