ImPassion130 brings breast cancer into the immunotherapy era

Medical writer: Dr. Giuseppe Curigliano

2018 was a pivotal year in breast cancer research, with the phase III ImPassion130 trial bringing breast cancer into the immunotherapy era. Schmid et al.¹ demonstrated a substantial overall survival (OS) benefit in patients with PD-L1–positive metastatic triple-negative breast cancer (TNBC) by the addition of the anti–PD-L1 agent atezolizumab to first-line chemotherapy with nab-paclitaxel.

At median follow-up of 12.9 months, the median progression-free survival (PFS) in the ITT population was significantly improved with the addition of atezolizumab (5.5 vs. 7.2 months; HR 0.80, 95% CI [0.69, 0.92]; P = 0.002). A PFS benefit with atezolizumab was also observed in the PD-L1–positive population (5.0 vs. 7.5 months; HR 0.62, 95% CI [0.49, 0.78]; P < 0.001). An interim OS analysis was performed, and the OS difference was not statistically significant in the ITT population (median OS, 17.6 to 21.3 months; HR 0.84, 95% CI [0.69, 1.02]; P = 0.08). However, an impressive median OS increase of 9.5 months was observed with the addition of atezolizumab in the PD-L1–positive population (15.5 vs. 25.0 months; HR 0.62, 95% CI [0.45, 0.86]).

According to these data, is immunotherapy transformative for metastatic TNBC? Many open questions can be raised from the current trial. What is the best way to test the tumor for PD-L1 expression since this subgroup of patients derived benefit from atezolizumab? Is nab-paclitaxel the ideal partner for an immune checkpoint inhibitor? Did we miss an atezolizumab monotherapy arm that might be a good option for certain subset of patients? Should we be more focused on OS rather than PFS? What can we learn from the neoadjuvant setting?

The positive result in the PD-L1–positive subgroup suggests that we need to enrich the study population. Therefore, we need to define the immunogram of patients with breast cancer who are most likely to respond to immune checkpoint inhibitors. The objective response rate (per RECIST) was numerically higher with the addition of atezolizumab in the ITT population (56% vs. 46% without atezolizumab) and PD-L1–positive population (59% vs. 43% without atezolizumab), and more complete responses were observed with atezolizumab than without (ITT: 7% vs. 2%; PD-L1–positive group: 10% vs. 1%). A companion diagnostic test assessed PD-L1 expressed only on immune cells.

Conclusion

It is an exciting time in the treatment of TNBC. The multiple ongoing trials may shed light on breast cancer immune response biomarkers and determine whether a multidimensional immunogram could predict efficacy better than the current PD-L1–based unidimensional immunogram.

1. Schmid P, et al. New Engl J Med . 2018;379:2108-21

Posted on 15 July 201925 March 2021