Triple-negative: a new targeted weapon?

By Ana Espino | Published on October 28, 2025 | 3 min read


Triple-negative breast cancer (TNBC) accounts for about 15% of all breast cancers. Its prognosis is poor, particularly in the metastatic stage. Its biology—characterized by the absence of hormone receptors (ER, PR) and HER2—limits the effectiveness of conventional targeted therapies. In addition, recurrence is common, and patients have few therapeutic options after the first lines of chemotherapy, which are often taxane-based.

Among the potential therapeutic approaches, the PI3K/AKT/PTEN pathway, which is frequently altered in these tumors, could represent a promising target. Ipatasertib, an oral selective AKT inhibitor, has already shown some efficacy, particularly when combined with paclitaxel. However, taxane-related toxicities can limit their use.

In this context, this study was initiated to evaluate the safety, tolerability, and preliminary efficacy of ipatasertib combined with three non-taxane chemotherapies, carboplatin, vinorelbine, or capecitabine, in patients with previously treated locally advanced or metastatic TNBC.  

What did the study find?

Eighty-five patients with advanced TNBC were enrolled and randomly assigned to three treatment arms:

• Ipatasertib (400 mg/day, 3 weeks on / 1 week off) combined with carboplatin (n=34);
• Vinorelbine (n=30);
• Capecitabine (n=21).

Treatments were administered in 28-day cycles. The study assessed the efficacy and tolerability of these combinations. Patients could have received up to two prior lines of treatment.

The results showed an objective response rate (ORR) of 29.4% in the ipatasertib + carboplatin arm, compared with 13.3% for vinorelbine and 10.7% for capecitabine. The median duration of response was 4.6 months in the carboplatin arm, confirming this combination as the most promising. Notably, patients with PI3K/AKT/PTEN pathway alterations responded better to treatment, suggesting potential value as a targeted therapy.

In terms of tolerability, the most common grade ≥3 adverse events included diarrhea (up to 28%), neutropenia (13–20% depending on the arm), as well as nausea, fatigue, and mucositis, which were less frequent. Overall, toxicities were considered manageable, with no new safety signals, although some treatment interruptions were required due to gastrointestinal effects.  

What does this mean?

This study shows that the combination of ipatasertib + carboplatin demonstrates promising antitumor activity in previously treated advanced TNBC, especially in tumors with targetable molecular alterations (PI3K/AKT/PTEN pathway). These findings support the relevance of a precision medicine approach in this heterogeneous and difficult-to-treat population.

However, the other combinations tested (with vinorelbine or capecitabine) produced more modest responses, limiting their clinical usefulness. Future research will include a phase III trial comparing ipatasertib + carboplatin with chemotherapy alone, as well as a more precise molecular stratification of patients based on tumor genetic alterations. The use of predictive biomarkers will also be crucial to refine therapeutic indications.     

Read next: TNBC: exploring the global landscape of biomarkers and therapeutic prospects