Real-World Relationship of Early End Points to Survival End Points in Patients with Resectable Non-Small-Cell Lung Cancer

Abstract

Aim: Pathologic response has been shown to be a promising surrogate for survival in non-small-cell lung cancer. We examined the real-world relationship between these end points in patients with resectable stage IB-IIIA non-small-cell lung cancer receiving neoadjuvant chemotherapy/chemoradiotherapy (CT/CRT). Methods: Electronic health records/medical charts were analyzed. Overall and event-free survival (OS/EFS) were assessed by Kaplan-Meier stratified by pathologic response. Associations between the end points were assessed by Cox analyses. Results: A total of 425 patients were selected for the study; 147 and 278 received CT and CRT, respectively. Pathologic complete response (pCR) was associated with longer OS (adjusted HR = 0.50; 95% CI: 0.29–0.85) and EFS (adjusted HR = 0.44; 95% CI: 0.28–0.68) versus no pCR, and EFS was associated with OS (HR = 0.51, 95% CI: 0.38, 0.69). Conclusion: In patients receiving neoadjuvant CT/CRT, pCR and EFS were associated with improved survival in this real-world dataset.

Neoadjuvant Chemo-Immunotherapy for Early-Stage Non–Small Cell Lung Cancer

“…Moreover, EFS and particularly pCR are considered reliable surrogates for OS. [7][8][9] We estimated and quantified a consistent association between neoadjuvant ICI-chemotherapy and 2-year EFS and pCR across the 8 RCTs so far reported. [13][14][15][16][21][22][23][24] This association was irrespective of patients' clinical characteristics, tumor features, main prognostic factors, and type of platinumbased chemotherapy for the neoadjuvant chemoimmunotherapy regimen, although the HRs varied in some subgroups.…”

“…The other studies investigated pCR or major pathologic response and/or EFS as primary end points with different therapeutic strategies, such as not including adjuvant ICI therapy, using 3 or 4 neoadjuvant ICI-chemotherapy cycles, or using either carboplatin- or cisplatin-based chemotherapy. Moreover, EFS and particularly pCR are considered reliable surrogates for OS …”

“…6 The latter is recognized as a potential surrogate for overall survival (OS). [7][8][9] This led to the approval of a neoadjuvant ICI regimen for resectable NSCLC by the US Food and Drug Administration and European Medicines Agency. [10][11][12] Some studies indicated greater benefits in EFS and/or pCR in patients with increased programmed cell death ligand 1 (PD-L1) expression in tumor cells.…”

“…Randomized clinical trials (RCTs) have investigated the use of neoadjuvant ICIs in combination with platinum-based chemotherapy (ICI-chemotherapy) in resectable NSCLC, demonstrating a prolongation of event-free survival (EFS) and a significant increase in pathologic complete response (pCR) . The latter is recognized as a potential surrogate for overall survival (OS) . This led to the approval of a neoadjuvant ICI regimen for resectable NSCLC by the US Food and Drug Administration and European Medicines Agency…”

“… 6 The latter is recognized as a potential surrogate for overall survival (OS). 7 , 8 , 9 This led to the approval of a neoadjuvant ICI regimen for resectable NSCLC by the US Food and Drug Administration and European Medicines Agency. 10 , 11 , 12…”