Triple Therapy Demonstrates Efficacy for Advanced TNBC Patients

A recent phase 2 clinical trial, known as the ATRACTIB study (NCT04408118), has shown promising results for a novel triple therapy aimed at treating advanced triple-negative breast cancer (TNBC), regardless of programmed cell death-ligand 1 (PD-L1) status. The trial, which enrolled 100 female patients, focused primarily on those with PD-L1–negative tumors, a subset known for its poor prognosis and limited treatment options.

Triple-negative breast cancer is characterized by the absence of hormone receptors for estrogen and progesterone, as well as the lack of human epidermal growth factor receptor 2 (HER2) expression. This aggressive form of cancer often exhibits a poor overall survival rate compared to other breast cancer subtypes. Current therapeutic strategies typically rely on the presence of PD-L1 expression, with checkpoint inhibitors proving beneficial primarily in PD-L1–positive cases. However, patients with PD-L1–negative TNBC face significant challenges, particularly in finding effective treatments beyond standard chemotherapy.

The ATRACTIB trial evaluated the combination of atezolizumab (Tecentriq), paclitaxel, and bevacizumab (Avastin) as a first-line treatment for advanced TNBC. Of the 100 patients enrolled, 97.6% had evaluable tumors that were PD-L1–negative, underscoring the trial's focus on this difficult-to-treat subgroup. The primary endpoint of investigator-assessed progression-free survival (PFS) was met, with a median PFS of 11.0 months (95% CI, 9.0–13.4; P < .001). In patients with confirmed PD-L1–negative tumors, the median PFS was 9.3 months (95% CI, 7.8–13.2).

The results also indicated a promising objective response rate of 63.0% (95% CI, 52.8%–72.4%), with 14% of patients achieving complete responses and 49% experiencing partial responses. Additionally, the median overall survival (OS) was reported at 27.4 months (95% CI, 23.4–37.4), which compares favorably to historical data from other trials involving PD-L1–negative populations. For instance, the IMpassion130 trial had a median PFS of only 5.6 months and a median OS of 19.7 months in a similar patient cohort.

While the ATRACTIB trial's results are promising, the safety profile of the triplet combination was also a key focus. All participants experienced at least one treatment-emergent adverse event (TEAE), with 61% experiencing grade 3 or 4 TEAEs. The most frequent TEAEs included fatigue (63%), neurotoxicity (46%), and diarrhea (44%). Notably, no treatment-related deaths or new safety signals were identified, aligning with the known safety profiles of the individual agents involved.

The inclusion of bevacizumab in the combination therapy is significant; it is an anti-VEGF antibody that has shown potential immunomodulatory properties and may enhance the antitumor activity of immune checkpoint inhibitors. The ATRACTIB findings suggest that integrating antiangiogenic agents might extend the benefits of immunotherapy to a broader patient population, particularly those traditionally categorized as difficult to treat.

Despite the study's strengths, including its substantial sample size for a phase 2 trial, the single-arm design limits the assessment of the individual contributions of each treatment component. Future studies may need to explore the synergistic effects of these agents more formally. As the treatment landscape for TNBC continues to evolve, with the emergence of new therapies such as antibody-drug conjugates, the need for effective combination strategies remains paramount.

In conclusion, the ATRACTIB trial offers hope for patients suffering from advanced TNBC, particularly those with PD-L1–negative tumors, by presenting a potentially effective treatment option that could reshape future therapeutic approaches. As researchers continue to explore innovative treatment combinations, the findings from this trial may pave the way for improved outcomes in this challenging cancer subtype.