Results from POPLAR: Efficacy, Safety, and Predictive Biomarker Results From a Randomized Phase 2 Study Comparing MPDL3280A vs Docetaxel in NSCLC

Conference Correspondent - ASCO 2015 - Lung Cancer


MPDL3280Aor atezolizumab (Atezo) is ahumanized anti-PDL1 monoclonal antibody that has demonstrated promising response rates in NSCLC correlated with PD-L1 expression on tumor-infiltrating immune cells (IC) and/or tumor cells (TC).a This suggests that PD-L1 expression on TC and IC is a potential predictive biomarker for Atezo in NSCLC. In this presentation by Spira and colleagues,b 287 previously treated patients with metastatic NSCLC were stratified by PD-L1 IC status, histology (34% squamous and 66% nonsquamous), and prior lines of therapy, and randomized to receive Atezo or docetaxel (DOC). PD-L1 expression was centrally evaluated by immunohistochemistry (IHC) using the SP142 antibody assay. Patients were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3 based on the number of PD-L1+ tumor-infiltrating TC or IC. After a median follow-up of 12 months, the primary endpoint was overall survival (OS), with progression-free survival (PFS) and objective response rate (ORR) as secondary endpoints. In this interim analysis, improved efficacy over DOC was observed with Atezo in patients with increasing PD-L1 expression (e.g., OS HR= 0.46; PFS HR= 0.56 and ORR, 38% vs 13% in TC3 or IC3 pts), while patients with the lowest PD-L1 levels (TC0 and IC0) did not appear to benefit from Atezo over DOC (OS HR= 1.12; ORR 8% for Atezo vs. 10% for DOC). Safety was evaluable for 277 patients. Despite a longer median treatment duration for Atezo (3.6 months vs 2.1 months for DOC), fewer patients receiving Atezo (39%) vs DOC (52%) experienced Grade ? 3 adverse events. This was the first randomized study in nonsquamous and squamous NSCLC to demonstrate that inhibition of the PD-L1/PD-1 pathway may lead to improved survival. Furthermore, these data showed that PD-L1 biomarker selection, using a highly sensitive and specific IHC assay measuring PD-L1 on both TC and IC, can identify patients most likely to derive improved OS, PFS and ORR from Atezo and those that are unlikely to benefit from Atezo versus standard of care. A phase 3 study in this patient population is ongoing.

  1. Horn L, et al. ASCO 2015. Abstract 8029.
  2. Spira AI, et al. ASCO 2015. Abstract 8010.