Trastuzumab deruxtecan improves PFS in metastatic breast cancer with rapid progression

06 Jan 2025 bởiStephen Padilla
Trastuzumab deruxtecan improves PFS in metastatic breast cancer with rapid progression

Treatment with trastuzumab deruxtecan (T-DXd) results in longer progression-free survival (PFS) in patients with hormone receptor–positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC) compared with physician’s choice of chemotherapy, according to the results of the phase III DESTINY-Breast06 study presented at SABCS 2024. In addition, no new safety signals have been identified.

“T-DXd demonstrated a clinically meaningful efficacy benefit versus [chemotherapy], with a >12-month median PFS across first-line endocrine therapy (ET) plus CDK4/6 inhibitor time-to-progression (TTP) subgroups, notably in patients with rapid (<6 months) progression,” said lead author Dr Aditya Bardia, professor of medicine in hematology/oncology at the David Geffen School of Medicine at UCLA, US.

In the DESTINY-Breast06 study, Bardia and his team randomized 866 patients to receive either T-DXd 5.4 mg/kg given intravenously every 3 weeks or chemotherapy (59.8-percent capecitabine, 24.4-percent nab-paclitaxel, 15.8-percent paclitaxel).

Endocrine therapy

Participants had previously received ≥2 lines of endocrine-based therapy for mBC or 1 line if disease progression occurred within 24 months of adjuvant ET or within 6 months of first-line ET plus CDK4/6 inhibitor (the latter considered rapid progression). Subgroups were TTP on first-line ET plus CDK4/6 inhibitor and primary versus secondary endocrine resistance (per 5th ESO-ESMO ABC criteria).

Bardia and colleagues assessed the following outcomes: PFS, confirmed objective response rate (ORR), and duration of response (DOR) by blinded independent central review in the ITT, and safety.

Of the participants, 713 had HER2-low and 153 had HER2-ultralow disease. The intent-to-treat (ITT) population included 89.3 percent of patients who received at least one prior line of ET plus CDK4/6 inhibitor. The TTP analysis included 65.8 percent of patients in ITT, of which 124 had <6-month, 112 had 6‒12-month, and 334 had >12-month TTP. [SABCS 2024, abstract LB1-04]

Patient number, demographics, clinical characteristics at baseline were balanced across subgroups. In the TTP subgroup, 73 patients (<6 months; 58.9 percent), 26 (6‒12 months; 23.2 percent), and 24 (>12 months; 7.2 percent) received T-DXd or chemotherapy as a second-line treatment following one line of ET plus CDK4/6 inhibitor.

Survival benefit

T-DXd induced longer PFS than chemotherapy in patients with rapid progression (<6 months; median, 14.0 vs6.5 months; hazard ratio [HR], 0.38, 95 percent confidence interval [CI], 0.25‒0.59). A similar trend was observed in the 6‒12-month (13.2 vs 6.9 months; HR, 0.69, 95 percent CI, 0.43‒1.12) and >12-month subgroups (12.9 vs 8.2 months; HR, 0.67, 95 percent CI, 0.51‒0.88).

ORR was significantly better with T-DXd, compared with chemotherapy, in patients with <6-month (67.7 percent vs 25.4 percent), 6‒12-month (60.0 percent vs 28.8 percent), and >12-month TTP (59.5 percent vs 33.1 percent). Likewise, T-DXd had better DOR than chemotherapy across TTP subgroups (<6 months: median, 11.1 vs 7.3 months; 6‒12 months: 13.7 vs 11.5 months; >12 months: 15.7 vs 11.1 months).

“Efficacy outcomes were consistent in patients with investigator-assessed primary and secondary endocrine resistance,” according to Bardia.

In terms of safety, the incidence of grade ≥3 treatment-emergent adverse events associated with T-DXd versus chemotherapy across TTP subgroups was consistent with the overall safety population (<6 months: 55.4 percent vs 42.2 percent; 6‒12 months: 59.3 percent vs 40.8 percent; >12 months: 45.8 percent vs 42.9 percent).

These findings “highlight the potential role of T-DXd as an early-line treatment after ≥1 line of endocrine-based therapy for patients with hormone receptor–positive, HER2-low or -ultralow mBC,” Bardia said.