446PD Second-line afatinib vs erlotinib for patients with squamous cell carcinoma of the lung in LUX-Lung 8: analysis of tumor and serum biomarkers

Abstract

Background In LUX-Lung 8 (LL8), second-line afatinib (A) significantly improved PFS and OS vs erlotinib (E) in patients (pts) with squamous cell carcinoma of the lung (N=795).We report exploratory molecular analyses (n=245) and immunohistochemistry (IHC; n=288) of LL8 tumor samples to assess frequency of short variants (SVs) and copy number alterations (CNAs) in cancer-related genes, and clinical utility of genomic alterations or EGFR expression levels as predictive biomarkers. We also assessed the predictive utility of the prospectively validated VeriStratVR (VS) test, a serum protein test (n=675). Methods Tumor samples were analyzed by FoundationOneTM next-generation sequencing. EGFR positivity (by IHC) was defined as staining in > 10% of cells (Method 1) or H-score >200 (Method 2). Pretreatment serum samples were assigned as VS- Good (VS-G) or VS-Poor (VS-P) by mass spectrometry signature. Cox regression analysis was used to correlate PFS/OS with genomic alterations (individual or grouped, e.g. ErbB family), EGFR expression, and VS status. Results The frequency of ErbB family alterations was low (SVs: EGFR 6.5%, HER2 4.9%, HER3 6.1%, HER4 5.7%; CNAs: EGFR 6.9%, HER2 3.7%). No individual genetic or ErbB family alterations were predictive of PFS/OS. Treatment (tx) benefit from A vs E was consistent in all molecular subgroups. EGFR expression was not predictive of PFS/OS benefit (Table). PFS and OS were improved (p < 0.0001) in the VS-G vs VS-P group (Table). VS-G pts had significantly longer PFS (median 3.3 vs 2.0 mos) and OS (median 11.5 vs 8.9 mos) with A vs E, while VS-P pts had no significant difference in PFS/OS with A vs E (Table). There was no significant interaction between tx arms and VS classification. Conclusions No biomarkers were identified that predicted benefit with A over E in LL8 pts. A is a tx option in this setting irrespective of tumor characteristics. However, pt outcome strongly depends on VS status. Conclusions No biomarkers were identified that predicted benefit with A over E in LL8 pts. A is a tx option in this setting irrespective oftumor characteristics. However, pt outcome strongly depends on VS status. Table: 446PDTabled 1Table: 446PDPFS and OS in patients assessed by IHC and VeriStratPFSOSHR95% CIHR95% CIIHC Method 1EGFR + (A: 82%; E: 86%)0.760.57-1.020.840.63-1.12EGFR- (A: 18%; E: 14%)0.870.45-1.680.770.40-1.51IHC Method 2EGFR+ (A: 28%; E: 37%)0.780.47-1.300.690.42-1.13EGFR- (A: 72%; E: 63%)0.760.55-1.050.690.42-1.13VeriStratVS-G vs VS-P0.650.54-0.770.410.35-0.49A vs E (VS-G group)0.730.59-0.920.790.63-0.98A vs E (VS-P group)0.970.73-1.270.90.70-1.16 Open table in a new tab Clinical trial indentification NCT01523587 Legal entity responsible for the study N/A Funding: Boehringer Ingelheim Disclosure J-C. Soria: Honoraria: BI, Roche. E. Felip: Honoraria: Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene Consultancy/Advisory board: Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene Speakers bureau: BMS, Novartis, Roche. A. Ardizzoni: Advisory board: BI Honoraria: BMS, MSD. S.M. Gadgeel: Advisory board: Boehringer-Ingelheim, Genentech/Roche, Astra-Zeneca. N. Dupuis: Employment Biodesix, Inc. Stock ownership or options Biodesix, Inc. N.J. Gibson, N. Kr€amer: Employment: Boehringer Ingelheim Pharma GmbH & Co. KG. C. Bu¨hnemann: Employment: BI. F. Solca: Employment: Boehringer Ingelheim RCV GmbH & Co KG. E. Ehrnrooth: Employment: Boehringer Ingelheim. G. Goss: Advisory board: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer. All other authors have declared no conflicts of interest.