PD-L1 Immune Cell Expression Critical to Atezolizumab Efficacy in TNBC

Wayne Kuznar
Published: Thursday, Dec 06, 2018

Among patients with CD8+ T cells in their tumors, benefit on PFS and OS was observed only if their tumors were also PD-L1 immune cell-positive. The HRs in this group were 0.33 (95% CI, 0.13-0.67; P = .03) for PFS and 0.25 (95% CI, 0.06-1.02; P = .05) for OS with combination therapy.

In contrast, the HRs in patients with CD8+ tumors but PD-L1 immune cell negativity were 0.89 (95% CI, 0.66-1.20; P = .45) for PFS and 0.77 (95% CI, 0.50-1.17; P = .21) for OS. Among the 280 patients who were positive for both CD8+ expression and PD-L1 immune cell expression, significant benefit was derived from the combination for both PFS (HR, 0.61; 95% CI, 0.46-0.80; P £.005) and OS (HR, 0.55; 95% CI, 0.38-0.80; P ≤ 005).

Similarly, PD-L1 immune cell-negative patients whose tumors had stromal TILs derived no clinical benefit from the addition atezolizumab—the HR for PFS was 0.99 (95% CI, 0.62-1.57; P = .97) and the HR for OS was 1.53 (95% CI, 0.76-3.08; P = .24). In contrast, patients whose tumors contained stromal TILs and expressed PD-L1 on immune cells had a significant improvement in PFS (HR 0.53; 95% CI, 0.38-0.74; P ≤.005) and OS (HR 0.57; 95% CI, 0.35-0.92; P = .02) with the chemoimmunotherapy.

Of patients evaluable for BRCA mutation status, 15 had BRCA1/2 mutant tumors. These patients had a significant improvement in PFS with chemoimmunotherapy only if their tumors were also PD-L1 immune cell-positive (HR, 0.45; 95% CI, 0.21-0.96; P = .04). Investigators also observed a trend toward improvement in OS (HR 0.87; 95% CI, 0.26-2.85; P = .82).

“I would note that these data are somewhat limited by the small patient numbers,” Emens said. “However, they do show that mutations in BRCA- and PD-L–expressing immune cells are independent biomarkers, and patients with BRCA1 or -2 mutated tumors derived clinical benefit only if their tumors were also PD-L1 immune cell-positive.”

In the primary analysis, as presented previously, atezolizumab plus nab-paclitaxel resulted in a statistically significant PFS benefit in the intent-to-treat (ITT) population compared with placebo plus nab-paclitaxel (HR, 0.80; 95% CI, 0.69-0.92; P = .0025) and a trend toward improved OS (HR, 0.84; 95% CI, 0.69-1.02; P = .0840).2

Among patients with PD-L1–positive tumors, both PFS (HR, 0.62; 95% CI, 0.49-0.78; P <.001) and OS (HR, 0.62; 95% CI, 0.45-0.86) were clinically meaningful with the addition of atezolizumab.

In the PD-L1 immune cell-positive subpopulation, the median PFS was 7.5 months in patients randomized to the atezolizumab-nab-paclitaxel combination compared with 5.0 months in patients assigned to placebo plus nab-paclitaxel (HR, 0.62; P <.0001).

References

  1. Emens LA, Loi S, Rugo HS, et al. IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer. In: Proceedings from the 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. Abstract GS1-04.
  2. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;3 79:2108-21.
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