Multi-institution real world analysis of patients with non-small cell lung cancer (NSCLC) treated with standard of care (SOC) neoadjuvant chemo-immunotherapy (chemoIO).
Authors: Cooper Alissa Jamie , Gorria Teresa , Conroy Michael R , Ricciuti Biagio , Pecci Federica , Aldea Mihaela , Anagnostou Valsamo , Shaverdian Narek , Bott Matthew , Forde Patrick M. , Awad Mark M. , Schoenfeld Adam Jacob , Chaft Jamie E. 
Published: June 2024

8049

Background: The approval of neoadjuvant chemoIO transformed the treatment paradigm for patients (pts) with early-stage, resectable NSCLC. Here we present a multi-institution, real world analysis of pts treated with neoadjuvant chemoIO as SOC. Methods: This was a retrospective analysis performed across 3 academic institutions. Pts were eligible if they received neoadjuvant chemoIO as SOC therapy for NSCLC with intent to proceed to surgery. Results: 107 pts were included. Median age was 69 (range, 45-84); 47% were male and 83% were white. 84% were former/current smokers with median 35 pack year history. ECOG scores of 0/1/2 at treatment start were 55%/44%/1%, respectively. Histologies were 65% adenocarcinoma, 27% squamous, and 7% other. PD-L1 scores (in 93% of pts) were ≥ 50% in 30%, and median TMB (in 73% of pts) was 8.2 (range, 0-56). Of tumors with next generation sequencing (81%), 45% had KRAS mutation and 18% had other oncogenic driver present. Pts were clinical stage IB (0.9%), IIA (6%), IIB (24%), IIIA (60%), or IIIB (8%); 47% had N2 disease and 3% had N3. 78% of pts underwent ≥ 3 cycles of chemoIO, with most pts receiving carboplatin (70%). 11 pts (10%) experienced grade ≥ 3 immune-related adverse events, 72% of which were pre-op. 82 pts (77%) proceeded to surgical resection. Of those who did not undergo surgery, 68% were stage III. The most common reason for no surgery was progression (PD)/unresectability (52%), followed by operability (36%) and pt decision (8%). 2 pts (2%) proceeded to surgery but had unresectable tumors. Median interval between last cycle of induction and surgery was 43 days (d) (range, 17-210); median length of stay was 4d (range, 1-21). 5 of 79 (6%) were readmitted within 30d. For pts without resection (27), 48% underwent chemoradiation (CRT), 26% RT alone, and 15% systemic therapy. 29 tumors (36%) demonstrated major pathologic response (MPR); of these, 16 (20%) had pathologic complete response (pCR). 2 pts had no decrement in viable tumor. Of 79 pts with adjuvant treatment data, 11% underwent RT alone, in combination with chemo, or in sequence with systemic therapy; 8% were recommended for RT but declined. 24% had systemic treatment including 14% IO, 6% targeted therapy, and 4% chemo. 18/107 pts (17%) had PD; 14/18 had stage III disease. PD occurred in 10/25 pts (40%) who did not have surgery; 6 of those had undergone definitive CRT or RT. PD occurred in 8/82 pts (10%) after surgery; of these, 5 had undergone adjuvant treatment at median 58d (range, 33-103). Conclusions: Real world analysis demonstrated older, frailer pts with more advanced disease than those enrolled on trial; lower chemoIO completion rates but comparable pCR and resection rates were seen. Further analyses will focus on outcomes of pts who did not undergo surgery.