Aisner, Dara L.

9090 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. [Table: see text]

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as “preferred interventions,” whereas others are categorized as either “other recommended interventions” or “useful under certain circumstances.”

Context.— The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR. Objective.— To describe the perspective of members of the Pulmonary Pathology Society (PPS) on the workup of lung allograft transbronchial biopsy and the diagnosis of acute cellular rejection and AMR in lung transplant. Data Sources.— Reports by the International Society for Heart and Lung Transplantation (ISHLT), experience of members of PPS who routinely review lung allograft biopsies, and search of literature database (PubMed). Conclusions.— Acute cellular rejection should be assessed and graded according to the 2007 working formulation of the ISHLT. As currently no specific features are known for AMR in lung allografts, the triple test (clinical allograft dysfunction, donor-specific antibodies, pathologic findings) should be used for its diagnosis. C4d staining might be performed when morphologic, clinical, and/or serologic features suggestive of AMR are identified.