Real world early experience of precision neoadjuvant systemic therapy in patients with resectable NSCLC: Single institution experiences and perspectives.
Authors: Park Cathleen , Toomey Kyra , Chen Joy , Godoy Luis , Cooke David , Brown Lisa , Riess Jonathan W. , Phan Chinh , Stollenwerk Nicholas , Zhou Chihong , Schneider Danielle , Nardo Lorenzo , Li Tianhong 
Published: June 2023

e20594

Background: The incidence of early-stage NSCLC is increasing with lung cancer screening. However, up to 55% of NSCLC patients (pts) who undergo curative surgery die of recurrence. Neoadjuvant chemoimmunotherapy increases pathological clinical response and reduces tumor recurrences in resectable NSCLC pts without known EGFR/ALK alterations in March 2022. The uptake of this practice is low and there is an unmet need in incorporating effective targeted therapies for driver oncogenes in pts with early-stage NSCLC. As precision neoadjuvant therapy holds the great promise in improving surgical and pathological outcomes and cure rate, the objective of this study was to develop a clinical workflow to timely coordinate the care between oncology specialties and biomarker testing in pts with early-stage NSCLC. Methods: This study included early-stage NSCLC pts with no biomarker testing (Cohort A, 15) and biomarker testing (Cohort B, 19). Driver genomic alterations with targeted therapy in the metastatic setting were identified by next generation sequencing (NGS). Descriptive analysis was used for the type and frequency of each mutation and unpaired t-test was used for time interval analysis. Results: In Cohort A, 10/15 (67%) pts received neoadjuvant chemotherapy (4) or chemoimmunotherapy (6) before surgery, 3 proceeded to surgery, and 2 received concurrent chemoradiation for unresectable tumor. Of 19 pts in Cohort B, 2 did not have biomarker testing due to small tumor size. Of the 17 pts who had NGS testing, 7 (41%) had a targetable oncogene: EGFR l858R (2), EML4-ALK (1), MET amplification (1), RET fusion (1), and EGFR E20in (2). Two received matched targeted therapies on clinical trials. Median (range) dates for NGS testing were 12 (6-44) and for NGS report from pathologic diagnosis were 48 (17-93). Barriers for getting a matched neoadjuvant therapy included no matched targeted therapy (2), tumor progression (1), unresectable tumor (1), and patient preference (1). Of the pts that underwent surgery, there was no statistically significant difference in median time (range) to diagnosis between Cohort A [N = 12, 33 (7-100) days] and Cohort B [N = 8, 34 (9-82) days] (p = 0.74). The median time (range) to surgery from pathologic diagnosis was shorter in Cohort B [78 (29-137)] than Cohort A [166 (56-201)] (p = 0.0002). The difference was due to more pts in the Cohort A receiving neoadjuvant therapy than the biomarker cohort [10/12 (83%) vs 2/7 (25%)]. Conclusions: In this analysis, time to pathological diagnosis were similar between Cohorts A and B. Time for NGS testing was also comparable for standard of care in metastatic disease. However, time to NGS results from pathological diagnosis was longer than anticipated in Cohort B, which is an area of improvement in our workflow in prospective clinical evaluation for precision neoadjuvant treatment of early-stage NSCLC.