Efficacy, safety, and biomarker results of trastuzumab emtansine (T-DM1) in patients (pts) with previously treated HER2-overexpressing locally advanced or metastatic non-small cell lung cancer (mNSCLC).

<jats:p> 8509 </jats:p><jats:p> Background: T-DM1 is an antibody-drug conjugate approved for HER2-positive metastatic breast cancer. We report primary results from a fully enrolled, ongoing phase 2 study (NCT02289833) of pts with previously treated HER2-overexpressing mNSCLC who received single-agent T-DM1. Methods: Eligible pts had HER2-overexpressing mNSCLC and were previously treated with platinum-based therapy. Pts received T-DM1 3.6 mg/kg every 3 weeks and were analyzed in 2 cohorts based on centrally determined HER2 status (immunohistochemistry [IHC]2+ vs IHC3+ [≥10% cells stained with 2+ or 3+ intensity, respectively]). HER2 amplification was assessed via ISH (HER2 gene ratio ≥2.0). The primary endpoint is objective response rate (ORR; proportion of pts with confirmed [≥4 weeks] complete or partial response per RECIST v1.1). Results: The clinical cutoff date for this analysis was Oct 26, 2016.Of 393 screened pts, 102 (27%) were IHC2+ and 29 (7%) were IHC3+. In total, 49 pts (IHC2+, n = 29; IHC3+, n = 20) received T-DM1. At cutoff, median follow-up was 16.3 (range 0.9*–22.4; * = censored observation) months. No IHC2+ pt had a response (0%, 95% CI 0–11.9); 4 IHC3+ pts had partial responses (20%, 95% CI 5.7–43.7) with a median duration of response of 7.3 (range 2.9–8.3) months. Median progression-free survival (PFS) in IHC2+ and IHC3+ pts was 2.6 (95% CI 1.4–2.8) and 2.7 (95% CI 1.4–8.3) months, respectively. At 6 months after start of study treatment, 9 pts (IHC2+, n = 4; IHC3+, n = 5) were still at risk for a PFS event. Median overall survival was 12.2 (95% CI 3.8–not estimable [NE]) months in IHC2+ pts and 12.1 (95% CI 9.3–NE) months in IHC3+ pts. Of 16 pts with HER2 amplification (IHC2+, n = 5; IHC3+, n = 11), 3 responded, all in the IHC3+ cohort (27.3%, 95% CI 6.0–61.0). Eleven pts (22%) experienced a grade 3–4 adverse event, with fatigue and dyspnea being the only events reported in > 1 pt (n = 2 each). Conclusions: This is the first study to report on the clinical activity of T-DM1 in HER2-overexpressing mNSCLC. Objective responses were observed in IHC3+ pts. Additional molecular analyses are underway to refine markers for optimal pt selection. Clinical trial information: NCT02289833. </jats:p>