Atezolizumab/Nab-Paclitaxel Induces Clinically Meaningful OS Benefit in PD-L1+ Locally Advanced or Metastatic TNBC

Hiroji Iwata, MD, PhD

The combination of atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) led to a clinically meaningful overall survival (OS) benefit in treatment-naïve patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who had PD-L1 expressing tumor-infiltrating immune cells (IC), according to data from the final OS analysis of the phase 3 IMpassion130 trial presented during the 2020 ESMO Asia Congress.¹

Results showed that patients with PD-L1 IC–positive disease had a 3-year OS rate of 36% with atezolizumab/nab-paclitaxel compared with 22% with placebo/nab-paclitaxel. The median OS was 25.4 months (95% CI, 19.6-30.7) with the atezolizumab combination and 17.9 months (95% CI, 13.6-20.3) with placebo/nab-paclitaxel (HR, 0.67; 95% CI, 0.53-0.86).

However, the OS boundary for statistical significance was not crossed in the intent-to-treat (ITT) population, precluding formal testing. In this group, the 3-year OS rate was 28% with atezolizumab/nab-paclitaxel versus 25% with placebo/nab-paclitaxel. The median OS was 21.0 months (95% CI, 19.0-23.4) in the investigational arm versus 18.7 months (95% CI, 16.9-20.8) in the control arm (HR, 0.87; 95% CI, 0.75-1.02; P = .077).

“Clinically meaningful OS benefit was observed in the PD-L1 IC–positive population,” said lead author of the study Hiroji Iwata, MD, PhD, vice director and chief of breast oncology at Aichi Cancer Center Hospital, clinical professor at Nagoya City University Medical School, during the presentation. “The OS results in the PD-L1 IC–positive population were consistent with the first and second interim analyses. With additional follow-up, atezolizumab and nab-paclitaxel [continued to be] tolerable.”

Results from the primary analysis of the trial showed that the combination prolonged progression-free survival (PFS) in both the ITT population and those with PD-L1 positivity.² The median PFS in the ITT population was 7.2 months with atezolizumab/paclitaxel versus 5.5 months with placebo/nab-paclitaxel (HR, 0.80; 95% CI, 0.69-0.92; P =.002). In those with PD-L1–positive tumors, the median PFS was 7.5 months versus 5.0 months, respectively (HR, 0.62; 95% CI, 0.49-0.78; P <.001).

Two interim OS analyses showed a clinically meaningful OS improvement was observed in patients with PD-L1 positivity, although this was not formally tested per the prespecified statistical analysis plan. At the first analysis, the median OS was 25.0 months with atezolizumab/nab-paclitaxel versus 15.5 months with placebo/nab-paclitaxel (HR, 0.62; 95% CI, 0.45-0.86). At the second analysis, the median OS in this population continued to be 25.0 months in the investigational arm versus 18.0 months in the control arm (HR, 0.71; 0.54-0.94).³

The global, double blind phase 3 IMpassion130 study enrolled patients with previously untreated metastatic TNBC with an ECOG performance status of 0-1 who had tumor tissue available for PD-L1 testing. Patients were randomized 1:1 to receive either atezolizumab plus nab-paclitaxel (n = 460) or placebo plus paclitaxel (n = 430). The co-primary end points of the study were PFS and OS.

Thirteen percent of patients (n = 60) in the ITT population received atezolizumab for up to 24 months, while 8% (n = 38) received it for 24 months or more at a mean dose intensity of 96%. Eight percent of patients in this cohort (n = 35) were given nab-paclitaxel up to 24 months and 5% (n = 22) received the agent for 24 months or more at a mean dose intensity of 86%.

Additional results from the final survival analysis presented during the meeting looked at OS by PD-L1 status and showed that those with PD-L1 negativity did not experience a benefit with the addition of atezolizumab. The median OS in both the investigational and control arm was 19.7 months (HR, 1.02; 95% CI, 0.84-1.24).

Regarding safety, in the ITT population, 51% (n = 233) of patients experienced grade 3/4 adverse effects (AEs) and 1% (n = 6) had a grade 5 AE. Eighty-eight patients (19%) who were given the atezolizumab regimen experienced an AE that led to withdrawal of any treatment; 37 patients discontinued treatment with atezolizumab (8%) and 85 discontinued nab-paclitaxel (19%).

The most common any-grade AEs reported in the ITT population included rash (36%; n = 165), hypothyroidism (18%; n = 84), and hyperthyroidism (5%; n = 22). The most common grade 3/4 toxicities were hepatitis (2%; n = 7), rash (1%; n = 5), and pneumonitis (< 1%; n = 2). No new safety signals were observed, concluded Iwata.

References

1. Iwata H, Emens LA, Adams S, et al. IMpassion130: final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: 2020 ESMO Asia Virtual Meeting; November 20-22, 2020; Virtual. Presentation ID 511 – FPN 49MO.
2. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108-2121. doi:10.1056/NEJMoa1809615
3. Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44-59. doi:10.1016/S1470-2045(19)30689-8