乌鸦传媒

SAN ANTONIO -- Women with HER2-positive early breast cancer may well have a new standard of care: Adjuvant trastuzumab emtansine (T-DM1, Kadcyla) significantly improved invasive disease-free survival in patients with HER2-positive early breast with residual disease after completion of neoadjuvant therapy, researchers reported here.

In the phase III KATHERINE study, the estimated invasive disease-free survival (IDFS) at 3 years was 88.3% among women on T-DM1 versus 77% for women taking trastuzumab (Herceptin, P<0.0001), according to Charles Geyer Jr., MD, of the Virginia Commonwealth University School of Medicine in Richmond, and colleagues.

At the interim analysis of 1,486 randomly assigned patients, invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%) for a hazard ratio for invasive disease or death of 0.50 (95% CI 0.39 -0.64, P<0.001), they wrote in the .

Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 arm and 15.9% of women in the trastuzumab arm, the authors noted.

"KATHERINE will likely form the foundation of a new standard of care in this population, and increase use of neoadjuvant therapy in HER2-positive early breast cancer," he said at a press conference at the San Antonio Breast Cancer Symposium, where the results were simultaneously presented.

"Patients receiving HER2-targeted monoclonal antibody therapy added to chemotherapy prior to surgery with clearance of invasive cancer in the breast and negative axially nodes have a favorable prognosis," Geyer said, "Patients with residual invasive disease in the breast or axillary nodes have a less favorable prognosis with an increased risk of recurrence and death."

KATHERINE enrolled women with centrally confirmed HER2-positive breast cancer who had completed neoadjuvant therapy, consisting of at least six cycles of chemotherapy and a minimum of 9 weeks of trastuzumab, Geyer said. The use of second HER2-targeted agents was allowed. After this therapy, if residual tumor was found in the breast or in the axillary lymph nodes, and the women could be randomized into the trial within 12 weeks of surgery, they were eligible for the study.

The researchers assigned 743 women to receive trastuzumab while another 743 women received T-DM1.

Geyer and colleagues looked at outcomes based an prespecified stratification, and found that treatment with T-DM1 was more effective than trastuzumab in women who had:

• Tumors that were operable or inoperable
• Any hormone receptor positivity
• Residual cancer in the lymph nodes after neoadjuvant therapy
• Received trastuzumab alone or multiple HER2-targeted therapies

"The benefit of T-DM1 for invasive disease-free survival was consistent across all key subgroups," Geyer said. "Additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival."

Adverse events were more frequent among women taking T-DM1, but most were mild to moderate, and grade ≥3 adverse events were infrequent. Decreased platelet counts reaching a level of thrombocytopenia occurred in 6% of the women, but Geyer said the adverse events were expected and were manageable.

"Of the 133 patients who discontinued T-DM1 early, 71 switched to trastuzumab, of whom 63 completed a total of 14 cycles of HER2-targeted treatment," the authors stated.

There were 42 deaths reported in the T-DM1 group and 56 in the trastuzumab group. The authors pointed out that overall survival analysis did not cross the early reporting boundary (HR for death 0.70, 95% CI 0.47-1.05).

The authors acknowledged that a potential study limitation was "the pragmatic decision to preferentially use the pretreatment core biopsy specimen of the primary tumor to centrally confirm positive HER2-status...Further analyses to define the rate of HER2 loss in the postsurgical specimens and the activity of T-DM1 in these patients are planned and possible, since paired specimens from more than two-thirds of the patients in the trial have been obtained."

"I do believe the KATHERINE study will change clinical practice," commented Jennifer Litton, MD, of the MD Anderson Cancer Center in Houston.

She told 乌鸦传媒 that previous studies of other agents in the adjuvant setting offered more modest results, "But what we saw with T-DM1 was a hazard ratio of 0.50 with a 3-year survival change of 11%, which really is much more significant. So I think for those patients who have not gotten a pathological complete response from their neoadjuvant therapies, I think we are going to see T-DM1 in the adjuvant setting."

Litton, who was not involved in the study, said she would not change treatment in patients already on a regime, "but for those patients who received standard neoadjuvant therapy for HER2-positive breast cancer, and did not get a pathological complete response, I think that offering T-DM1 would be reasonable, especially for the higher risk women."