National Cancer Centre Singapore, Singapore, Singapore
Stephanie Saw , Gillianne Lai , Aaron C. Tan , Siqin Zhou , Mei-Kim Ang , Wan-Teck Lim , Ravindran Kanesvaran , Wan Ling Tan , Tanujaa Rajasekaran , Johan Chan , Yi Lin Teh , Boon-Hean Ong , Angela M. Takano , Eng Huat Tan , Sze Huey Tan , Daniel Shao-Weng Tan
Background: Adjuvant Atezolizumab was recently approved in stage II-IIIA non-small cell lung cancer (NSCLC) with PD-L1 ≥1%. However, disease-free survival (DFS) benefit was mainly driven by PD-L1 ≥50% and among EGFR-mutated subgroup, atezolizumab did not demonstrate DFS benefit when PD-L1 0% patients were included. We sought to determine the prognostic value of PD-L1 score in early-stage EGFR-mutated NSCLC. Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1/1/2010 – 31/12/2019 who underwent curative surgery at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary endpoints were 2-year DFS and 5-year overall survival (OS) by Kaplan-Meier method. Results: 455 patients were included (267 EGFR-mutant; 188 EGFR-wildtype). Median age at diagnosis was 65 years, 52.3% (238/455) were males and 62.9% (286/455) were never-smokers. Adenocarcinomas comprised 92.1% (419/455) and 92.5% (421/455) had R0 resection. Stage IA comprised 42.4% (193/455), Stage IB 23.1% (105/455), Stage II 15.8% (72/455) and Stage IIIA 18.7% (85/455). Among EGFR-mutant, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-mutant and EGFR-wildtype was 55.8% (149/267) and 60.1% (113/188) respectively (p = 0.361). PDL1 ≥50% was significantly associated with higher stage at diagnosis among EGFR-mutant (p < 0.001) but not EGFR-wildtype (p = 0.319). At median follow up of 47 months, 178 patients had relapsed. Among EGFR-mutant, 2-year DFS comparing PD-L1 0% and PD-L1 ≥1% was 79.0% and 68.9% (p = 0.006) while 5-year OS was 87.6% and 70.6% (p = 0.006) respectively. 2-year DFS and 5-year OS by PD-L1 tertile (as shown in table) revealed that higher PD-L1 score was prognostically worse for both DFS and OS among EGFR-mutant. A similar trend was observed among EGFR-wildtype but did not reach statistical significance, apart from PD-L1 ≥50% which had significantly inferior DFS. Conclusions: Higher PD-L1 score was significantly associated with worse DFS and OS among early-stage EGFR-mutated NSCLC, possibly due to higher stage at diagnosis among PDL1 ≥50%. Our study highlights the poor prognosis of PDL1 ≥50% EGFR-mutated NSCLC in a pre-osimertinib era and underscores the importance of personalised risk-stratified adjuvant strategies.
2-year DFS (95% CI) | HR (95% CI) | p value | 5-year OS (95% CI) | HR (95% CI) | p value | ||
---|---|---|---|---|---|---|---|
EGFR-mutant | PD-L1 0% (n = 118) | 79.0% (70.3%-85.4%) | 1 | 87.6% (77.4%-93.4%) | 1 | ||
PD-L1 1-49% (n = 133) | 71.9% (63.4%-78.8%) | 1.58 (1.06-2.36) | 0.025 | 70.6% (56.5%-80.9%) | 2.38 (1.18-4.82) | 0.016 | |
PD-L1 ≥50% (n = 16) | 43.8% (19.8%-65.6%) | 2.89 (1.51-5.53) | 0.001 | 68.7% (34.3%-87.7%) | 3.14 (1.17-8.43) | 0.023 | |
EGFR-wildtype | PD-L1 0% (n = 75) | 76.8% (65.3%-84.9%) | 1 | 76.9% (62.5%-86.4%) | 1 | ||
PD-L1 1-49% (n = 71) | 70.6% (58.3%-80%) | 1.41 (0.85-2.35) | 0.179 | 61.7% (42.9%-75.9%) | 1.17 (0.61-2.21) | 0.639 | |
PD-L1 ≥50% (n = 42) | 42.2% (26.8%-56.8%) | 2.22 (1.30-3.81) | 0.004 | 57.2% (39.6%-71.4%) | 1.64 (0.85-3.17) | 0.141 |
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