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SAN ANTONIO -- Adjuvant treatment with ado-trastuzumab emtansine (Kadcyla), or T-DM1, demonstrated acceptable efficacy as a standalone treatment for women with stage I HER2-positive breast cancer, but failed to reduce clinically relevant toxicities, a randomized phase II trial found.

The so-called ATEMPT study met its primary efficacy endpoint, with 97.7% of patients treated with T-DM1 remaining disease free at 3 years (95% CI 96.2%-99.3%), Sara Tolaney, MD, MPH, of the Dana-Farber Cancer Institute in Boston, reported here at the (SABCS).

This 3-year disease-free survival (DFS) benefit was consistent regardless of hormone receptor (HR) status or tumor size:

• HR-positive: 97.5%

• HR-negative: 98.5%

• Tumor <1 cm: 98.5%

• Tumor ≥1 cm: 97.1%

Recurrence-free interval -- defined as no invasive local or regional recurrence, distant recurrence, or breast cancer death -- in the overall group of 383 patients treated with the antibody-drug conjugate reached 99.1% (95% CI 98.1%-100%).

But the rate of clinically relevant toxicities -- the study's other primary endpoint -- was no better than standard paclitaxel plus trastuzumab (TH), landing at 46% for both arms.

"T-DM1 was associated with very few recurrences in the study population," Tolaney said during an oral presentation. "T-DM1, however, was not associated with significantly fewer clinically relevant toxicities when compared to TH."

Among these clinically relevant adverse events (AEs), grade ≥3 non-hematologic events were similar between the T-DM1 and TH arms (10% vs 11%, respectively), as were rates of febrile neutropenia (0% vs 2%) and grade ≥4 hematologic events (1% vs 0%).

But Tolaney emphasized that there were differences in the toxicity profiles.

Grade ≥2 neurotoxicity was cut in half with T-DM1 (11% vs 23% with TH), yet patients on the standalone treatment were nearly three times as likely to discontinue treatment early for toxicity (17% vs 6% with TH). Only 9% discontinued T-DM1 early for toxicities that were protocol mandated, Tolaney pointed out, and most went on to trastuzumab following treatment cessation.

"It's also important to note that not all toxicities that are significant for our patients are captured in this clinically relevant toxicity endpoint, such as alopecia," said Tolaney, who added that patient reported outcomes (PROs) should also be considered when assessing tolerability and generally favored T-DM1, particularly during the time on therapy.

"Given the low event rate seen in this trial, T-DM1 may be considered an alternative treatment approach to TH for select patients with stage I HER2-positive disease who are concerned about specific TH-related side effects and who understand the potential for T-DM1 toxicities," Tolaney concluded. "There may be some patients and physicians however, who will want longer follow-up before adopting such an approach."

One of these physicians was SABCS invited discussant Jo Chien, MD, of the University of California San Francisco, who called the 3-year DFS rates achieved with T-DM1 "excellent," but cautioned against the approach.

"One year of T-DM1 is not ready to be a standard of care for small node-negative HER2-positive malignancies, due to short follow-up, high discontinuation rates, and high cost," said Chien. "For stage I disease, paclitaxel and trastuzumab remains the standard of care."

Reached for comment, Charles Shapiro, MD, of the Icahn School of Medicine at Mount Sinai in New York City, agreed, telling 口袋女优 that these data don't give him the confidence to offer T-DM1 as an alternative to trastuzumab and paclitaxel, despite the comparable efficacy.

"I don't think it's ready for prime time," said Shapiro. "If we wholesale decided to do T-DM1 it'd be very expensive also."

He pointed out that the investigators hypothesized that T-DM1 would deliver when it came to reducing overall toxicity, but there the study came up short.

The ATEMPT trial randomized 497 patients 3:1 to 17 cycles of T-DM1 (n=383) or weekly paclitaxel plus trastuzumab for 12 weeks followed by trastuzumab alone every 3 weeks for 13 cycles (n=114), with all treatments administered intravenously at standard doses.

Baseline characteristics were well balanced, and roughly three-fourths in each arm were HR-positive. In the TH arm, the 3-year DFS rate was 92.8% (95% CI 87.8%-98.1%), but Tolaney emphasized that the trial was not powered or designed for a comparison and that the 98.7% 3-year DFS results from the TH arm of the APT trial were a more apt comparison.

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