Evaluation of VeriStrat, a serum proteomic test, in the randomized, open-label, Phase 3 LUX-Lung 8 trial of afatinib versus erlotinib for the second-line treatment of advanced squamous cell carcinoma of the lung

Background

Treatment (tx) options for patients (pts) with squamous cell carcinoma (SCC) of the lung following chemotherapy are limited. In LUX-Lung 8 (LL8), in 795 pts with SCC of the lung, the irreversible ErbB family blocker, afatinib (A), significantly improved OS, PFS and DCR vs erlotinib (E), a reversible EGFR TKI. VeriStrat is a serum protein test that utilizes MALDI-TOF mass spectrometry to assign a ‘GOOD’ (VS-G) or ‘POOR’ (VS-P) classification and has shown prognostic and predictive utility for EGFR targeted agents in NSCLC.¹ Here, the predictive ability of VeriStrat was tested in LL8; OS was the primary efficacy variable.

Methods

Pre-tx serum samples, blinded to clinical outcome, were classified as VS-G or VS-P based on predefined reference groups. Clinical outcomes were analyzed with respect to VeriStrat status in the overall population (all pts with both clinical and VeriStrat data) and in pre-defined subgroups.

Results

675 pts were classified (VS-G: 412; VS-P: 263). In the VS-G group, median OS was 11.5 mo for A and 8.9 mo for E (HR [95% CI] 0.79 [0.63–0.98]; p = 0.03); median PFS was 3.3 mo for A and 2.0 mo for E (HR [95% CI] 0.73 [0.59–0.92]; p = 0.005). In the VS-P group, median OS was 4.7 mo for A and 4.8 mo for E (HR [95% CI] 0.90 [0.70–1.16]; p = n.s.); median PFS was 1.9 mo for both A and E (HR [95% CI] 0.96 [0.73–1.27]; p = n.s.). In pts treated with A, both OS (HR [95% CI] 0.40 [0.31–0.51]; p 

Conclusions

VeriStrat has a strong independent stratification effect in pts with relapsed/refractory SCC of the lung treated with A. In these difficult to treat pts, A conferred significantly better OS and PFS than E in the VS-G group, with a median OS of 11.5 mo vs 8.9 mo. 1. Gregorc V, et al. Lancet Oncol 2014;15:713–21.

Clinical trial identification

NCT01523587

Legal entity responsible for the study

Boehringer Ingelheim

Funding

Boehringer Ingelheim

Disclosure

G. Goss: Advisory board/board of directors: Astrazeneca, Pfizer, Boehringer Ingelheim, Lilly, Bristol Myers Squibb. E. Felip: Advisory board: Eli Lilly, Pfizer, Roche, BI Other: AZ, BMS, Novartis (Honoraria; lectures). A. Morabito: Other: Roche, AstraZeneca, Boehringer, Pfizer, Bayer (Honoraria). N. Dupuis: Stock ownership: Biodesix. V.K. Chand: Other: Current employer, EMD Serono; Previous employer BI. F. Solca: Other: Employed by BI. N. Krämer: Consultant to Boehringer Ingelheim Pharma GmBH & Co. KG, Biberach, Germany and receives compensation for these services. N. Gibson, E. Ehrnrooth: Employed by BI. J.C. Soria: Other: BI, Roche (honoraria). All other authors have declared no conflicts of interest.