Real-World Treatment Patterns and Timeliness of Clinical Care Pathway for Non-Small Cell Lung Cancer Patients in Austria: The PRATER Retrospective Study.

This was a retrospective study of the profile and initial treatments of adults diagnosed with early-stage (ES) non-small cell lung cancer (NSCLC) during January 2018-December 2021 at 16 leading hospital institutions in Austria, excluding patients enrolled in clinical trials. In total, 319 patients were enrolled at a planned ~1:1:1 ratio across StI:II:III. Most tested biomarkers were programmed death ligand 1 (PD-L1; 58% expressing), Kirsten rat sarcoma virus (KRAS; 22% positive), and epidermal growth factor receptor (EGFR; 18% positive). Of 115/98/106 StI/II/III patients, 82%/85%/36% underwent surgery, followed by systemic therapy in 9%/45%/47% of those [mostly chemotherapy (ChT)]. Unresected treated StIII patients received ChT + radiotherapy [43%; followed by immune checkpoint inhibitors (ICIs) in 39% of those], ICI ± ChT (35%), and ChT-alone/radiotherapy-alone (22%). Treatment was initiated a median (interquartile range) of 24 (7-39) days after histological confirmation, and 55 (38-81) days after first medical visit. Based on exploratory analyses of all patients newly diagnosed with any stage NSCLC during 2018-2021 at 14 of the sites (N = 7846), 22%/10%/25%/43% had StI/II/III/IV. The total number was not significantly different between pre-COVID-19 (2018-2019) and study-specific COVID-19 (2020-2021) periods, while StI proportion increased (21% vs. 23%; p = 0.012). Small differences were noted in treatments. In conclusion, treatments were aligned with guideline recommendations at a time which preceded the era of ICIs and targeted therapies in the (neo)adjuvant setting.

Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis.

In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement-positive non-small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive patients were considered responders. Median overall survival from lorlatinib initiation was 10.2 and 20.0 months for the ALK- and ROS1-positive groups, respectively. In the ALK-positive group, lorlatinib proved efficacy after both brigatinib and alectinib. Lorlatinib treatment was well tolerated. Later-line lorlatinib treatment can induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer.

Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC.

INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.