Clinicopathologic profile and treatment outcomes of non-sensitizing EGFR and HER2 (ERBB2) activating mutations in NSCLC: Results from a single-center retrospective study.

person Tejas Patil University of Colorado Cancer Center, Aurora, CO info_outline Tejas Patil, Rao Rashid Mushtaq, Sydney Marsh, Christine Azelby, Miheer Pujara, Dara Aisner, William T. Purcell, Erin Lynn Schenk, Paul A. Bunn, Jose Maria Pacheco, D. Ross Camidge, Robert Charles Doebele

Authors person Tejas Patil University of Colorado Cancer Center, Aurora, CO info_outline Tejas Patil, Rao Rashid Mushtaq, Sydney Marsh, Christine Azelby, Miheer Pujara, Dara Aisner, William T. Purcell, Erin Lynn Schenk, Paul A. Bunn, Jose Maria Pacheco, D. Ross Camidge, Robert Charles Doebele Organizations University of Colorado Cancer Center, Aurora, CO, Hurley Medical Center, Flint, MI, University of Colorado School of Medicine, Aurora, CO, University of Colorado Hospital, Aurora, CO, University of Colorado Comprehensive Cancer Center, Aurora, CO, Mayo Clinic, Rochester, MN, University of Colorado Denver, Aurora, CO, Baylor Coll of Medcn, Houston, TX, University of Colorado, Denver, CO Abstract Disclosures Research Funding Other Background: The clinicopathologic characteristics and optimal treatment strategies for non-sensitizing EGFR ( ns - EGFR ) and HER2 activating mutations in NSCLC remain unclear. Methods: Single-center retrospective study of patients seen at University of Colorado from 2008 – 2018 with stage IV NSCLC was performed. Clinicopathologic features and treatment outcomes of patients with ns-EGFR (Exon 18, Exon 20, L861Q) and HER2 mutations were collected. Best response to TKI was determined (RECIST v1.1). PFS was calculated using Kaplan-Meier method. Results: Among 359 patients, we identified 49 ns-EGFR (36 Exon 20 , 10 Exon 18 , 3 L861Q ) and 28 HER2 mutations (27 Exon 20 , 1 gene amplification) detected via NGS (65/77), real-time PCR (9/77), FISH (1/77) and undocumented (2/77). PDL1 > 50% was seen in 44% ns - EGFR and 57% HER2 . Adenocarcinoma was the most common histology (97%). Most patients were female (62%), never smokers (63%), and presented with metastatic disease (stage: I 5%, II 4%, III 6%, IV 85%). HER2+ NSCLC demonstrated a tropism for lung metastases (64%) that was significant when compared to EGFR Exon 19 , EGFR L858R , ALK, ROS1, and KRAS cohorts (p < 0.001). No differences were found when other metastatic sites were compared. Among evaluable patients, response rates to TKI therapy is shown. Aggregate median PFS on TKI for ns-EGFR and HER2+ NSCLC was 6 months compared to EGFR Exon 19 (15 months; p < 0.01; HR 0.4; CI 0.24 – 0.67) and EGFR L858R (22 months; p < 0.01; HR 0.27 and 0.8; CI 0.14 – 0.54). Aggregate median OS for ns-EGFR and HER2+ NSCLC was 28 months with no differences when compared to EGFR Exon 19 and L858R subgroups. Conclusions: HER2+ NSCLC appears to have a predisposition for lung metastases. Higher DCR was observed with newer generation TKIs, but novel targeted therapeutic approaches are needed as overall outcomes remain poor. All TKI Erlotinib Gefitinib Afatinib Osimertinib Clinical trials NS-E HER2 Total NS-E HER2 Total NS-E HER2 Total NS-E HER2 Total CR 0 0 0 0 0 0 0 0 0 0 0 0 PR 3 0 3 0 0 0 2 0 2 1 0 1 SD 12 2 14 4 0 4 1 0 1 7 2 9 PD 12 2 14 7 1 8 1 1 2 4 0 4 Total 27 4 31 11 1 12 4 1 5 12 2 14 ORR (%) 10 0 40 7 DCR (%) 55 33 60 71