Subtype-Tailored Treatment Bests Standard Chemotherapy in TNBC

Molecular subtype-based treatment can improve outcomes in patients with triple-negative breast cancer (TNBC), according to research published in The Lancet Oncology.

Researchers compared molecular subtype-based treatment to standard treatment for patients with TNBC in the phase 2 trial FUTURE-SUPER trial (ClinicalTrials.gov Identifier: NCT04395989).

The trial included 139 female patients with metastatic or recurrent TNBC. Most patients (n=104) had previously received neoadjuvant or adjuvant chemotherapy for early-stage breast cancer, but none had received nab-paclitaxel.

Treatment Details

The patients were randomly assigned to receive nab-paclitaxel alone (n=70) or nab-paclitaxel in addition to a subtype-based regimen (n=69). Nab-paclitaxel was given at 100 mg/m² on days 1, 8, and 15 of each 28-day cycle.

Of the 59 patients who had the immunomodulatory subtype, 30 received nab-paclitaxel alone, and 29 received nab-paclitaxel plus camrelizumab (200 mg on days 1 and 15) and famitinib (20 mg daily).

Of the 58 patients with the basal-like immune-suppressed (BLIS)/mesenchymal-like (MES) PI3K/AKT wild-type subtype, 30 received nab-paclitaxel alone, and 28 received nab-paclitaxel plus bevacizumab (10 mg/kg on days 1 and 15).

Of the 18 patients with the luminal androgen receptor (LAR) PI3K/AKT-mutant subtype, 9 received nab-paclitaxel alone, and 9 received nab-paclitaxel plus bevacizumab (10 mg/kg on days 1 and 15).

Of the 3 patients who had the LAR HER2-mutant subtype, 1 received nab-paclitaxel alone, and 2 received nab-paclitaxel plus pyrotinib (400 mg orally daily). There was 1 patient with the MES PI3K/AKT-mutant subtype. This patient received nab-paclitaxel plus everolimus (10 mg orally daily).

Results

At a median follow-up of 22.5 months, the median PFS was almost twice as long in patients who received subtype-based therapy as in those who received nab-paclitaxel alone — 11.3 months and 5.8 months, respectively (hazard ratio [HR], 0.44; 95% CI, 0.30-0.65; P <.0001).

Among patients with the immunomodulatory subtype, the median PFS was 15.1 months with subtype-based treatment and 6.5 months with control treatment (HR, 0.46; 95% CI, 0.25-0.85). Among patients with the BLIS/MES PI3K/AKT wild-type subtype, the median PFS was 9.1 months and 3.9 months, respectively (HR, 0.35; 95% CI, 0.19-0.63).

Among patients with the LAR PI3K/AKT-mutant subtype, the median PFS was 13.9 months with subtype-based treatment and 6.1 months with control treatment (HR, 0.48; 95% CI, 0.15-1.52). Sample sizes were too small for assessment of the other subtypes.

In the 118 patients who had measurable disease at baseline, the objective response rate was higher in the subtype-based treatment arm than in the control arm — 80.0% and 44.8%, respectively (odds ratio, 4.92; 95% CI, 2.17-11.15). The median duration of response was 12.0 months and 4.2 months, respectively (HR, 0.44; 95% CI, 0.26-0.78).

The median overall survival was not reached in either treatment arm (HR, 0.82; 95% CI, 0.38-1.56).

Nearly all patients had at least 1 treatment-related adverse event. The most common grade 3-4 events (in the subtype-based and control treatment arms, respectively) were neutropenia (30% vs 23%), anemia (7% vs 0%), and increased alanine aminotransferase (6% vs 1%).

“These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimization in patients with triple-negative breast cancer, suggesting a path for further clinical investigation,” the researchers wrote. “Phase 3 randomized clinical trials assessing the efficacy of subtyping-based regimens are now underway.”

Disclosures: This research was supported by Jiangsu Hengrui Pharmaceuticals. Two study authors are employed by the company. Please see the original reference for complete disclosures.

This article originally appeared on Cancer Therapy Advisor