SABCS Dr Slamon: final 10 yr results of non nthrocycline-containing herceptir egimen

[Lani]

vs anthracycline containing regimen ie TCH vs AC/TH


MEETING COVERAGE 12.12.2015 0 COMMENTS
10 Years On, Herceptin Still Rides High
Final analysis of 'landmark' trial finds sustained efficacy

by Michael Smith
North American Correspondent, MedPage Today

SAN ANTONIO -- Final results of a groundbreaking trial show a lasting benefit for a year of treatment with trastuzumab (Herceptin) in women with HER2-positive early stage breast cancer, a researcher said here.
After a decade of follow-up, the two trastuzumab arms of the BCIRG-006 trial show a "sustained and significant efficacy advantage" over a then-standard chemotherapy regimen of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), followed by docetaxel (Taxotere), according to Dennis Slamon, MD, of the University of California Los Angeles.
And the two trastuzumab regimens are not statistically different from each other in efficacy after a median of 10.3 years of follow-up, Slamon reported at the 38th San Antonio Breast Cancer Symposium here, where he presented the original practice-changing results.
On the other hand, there were important safety differences between the two trastuzumab regimens -- doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) or the combination of docetaxel, carboplatin (Paraplatin), and trastuzumab (TCH).
The equivalent efficacy, Slamon said, "comes at the cost" of more congestive heart failure, leukemia, and cardiac dysfunction in the AC-TH arm.
The original trial was a "landmark trial -- one of our key adjuvant trastuzumab studies that helped to firmly implant trastuzumab in the care of our HER2-positive patients," commented Minetta Liu, MD, of the Mayo Clinic in Minneapolis, who was not involved in the study.
The focus of the presentation, she told MedPage Today, was really on a long-time question: whether treatment can dispense with the anthracycline doxorubicin?
The safety differences between the two trastuzumab arms are mainly because of the adverse effects associated with doxorubicin, she noted, but Liu cautioned that they should be looked at carefully because the study wasn't powered to compare the trastuzumab arms directly.
Nonetheless, the accumulated evidence over 10 years might spark a "practice shift" away from the doxorubicin-containing regimen and toward TCH, she said, particularly in patients with other cardiac risk factors, such as diabetes or a family history of heart disease.
"I don't plan to abandon anthracyclines altogether," she said. "I will use them judiciously."
The bottom line, she said, is that both trastuzumab regimens work well, and doctors and patients can choose either with confidence. "We have two really good options for our HER2 patients in the early stage setting," she said.
The BCIRG-006 trial randomized 3,222 patients with HER2-positive early stage cancer to one of the three regimens, Slamon recalled, with the primary goal of seeing if there was a difference in disease-free survival, defined as breast cancer relapses, second primary tumors, or death from any cause.

The initial analysis showed a 51% improvement in disease-free survival for AC-TH and a 39% improvement for TCH over the AC-T arm, Slamon noted, and although the margins have narrowed, after a decade both experimental arms remain significantly better than the chemotherapy arm, with about a 28% edge in both cases.
The pattern was similar for high-risk patients -- those with positive lymph nodes and those with four or more positive nodes -- although the absolute rates of disease-free survival were lower than in the overall cohort, Slamon said,
Overall survival at 10 years is also better, Slamon reported, at 85.9% for AC-TH and 83.3% for TCH, compared with 78.7% for AC-T.
But there were important differences on the safety front, he said.
For grades 3 and 4 nonhematological adverse events, all three arms were roughly similar, although TCH patients had less arthralgia, myalgia, hand-foot syndrome, stomatitis, and vomiting, Slamon reported. Over all grades, the TCH patients had significantly less neuropathy, nail changes, and myalgia.

For the hematological toxicities, TCH patients had less neutropenia and leucopenia than those in the AC-TH arm, but more anemia and thrombocytopenia.
Cardiac toxicity differed markedly between the trastuzumab arms, Slamon reported, although there were no cardiac-related deaths on any arm. Specifically:
There were 21 cases of grades 3 and 4 congestive heart failure in the AC-TH arm, compared with four in the TCH arm (P=0.0005).
And there were 200 patients with at least a 10% relative decline in left ventricular ejection fraction (LVEF) in the AC-TH arm, compared with 97 among those getting TCH (P<0.0001).
The average LVEF had returned to baseline values after 10 years among TCH patients but remained depressed in patients in the other two arms, he reported.
The original BCIRG study had support from sanofi-aventis with additional support from Genetech, the National Cancer Institute, and the Cancer International Research Group. Slamon made no disclosures.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner