Relationship between level of PD-L1 expression and outcomes in the KEYNOTE-010 study of pembrolizumab vs docetaxel for previously treated, PD-L1–positive NSCLC
Pembrolizumab (pembro) is a humanized anti-PD1 monoclonal antibody approved in the United States for treating PD-L1–expressing advanced non–small-cell lung cancer (NSCLC) that progressed after platinum-based chemotherapy and an approved EGFR or ALK inhibitor. In the phase 3 KEYNOTE-010 study, pembro doses of 2 mg/kg and 10 mg/kg provided superior overall survival (OS) over docetaxel (doce) in patients with previously treated, PD-L1–positive advanced NSCLC (P
= 0.0008 for 2 mg/kg and P
<0.0001 for 10 mg/kg in the total population [tumor proportion score (TPS) ≥1%]).1
Baas and colleagues assessed OS, progression-free survival (PFS), and overall response rate (ORR) in KEYNOTE-010 when PD-L1 was further categorized as a TPS of 1% to 24%, 25% to 49%, 50% to 74%, and ≥75%.2
Patients with progression after ≥2 cycles of platinum-doublet chemotherapy and PD-L1 TPS ≥1% were randomized to pembro 2 or 10 mg/kg every 3 weeks or doce 75 mg/m2
every 3 weeks for 24 months or until progression, intolerable toxicity, or another reason. PD-L1 TPS 1% to 49% versus ≥50% was a randomization stratification factor. Response was assessed centrally per RECIST v1.1. Of the 2417 patients screened for PD-L1, 34% had TPS <1% and were ineligible. Of the 1478 patients who met all eligibility criteria and enrolled, PD-L1 TPS was 1% to 24% in 45.6% of patients, 25% to 49% in 11.6%, 50% to 74% in 15.3%, and ≥75% in 27.5%. Doce outcomes were similar regardless of TPS (Table
). However, for patients treated with pembro, OS, PFS, and ORR generally increased along with TPS, with the longest OS and PFS and highest ORR in patients with TPS ≥75% (Table). Moreover, pembro provided a longer OS than doce in all 4 TPS categories evaluated and a significantly higher ORR than doce in patients with TPS of 50% to 74% and 75% to 100%. The authors concluded that the prevalence of PD-L1–expressing tumors (those with TPS >1%) in this population was 66%, and that increasing PD-L1 expression was associated with more favorable outcomes with pembro, but not with doce, verifying PD-L1 as a predictive biomarker for pembro in NSCLC. However, pembro improved OS over doce even at the lowest TPS category assessed.
- Herbst RS, et al. Lancet. 2016;387:1540-1550.
- Baas P, et al. ASCO 2016. Abstract 9015.