TY - JOUR
T1 - Neoadjuvant immunotherapy for advanced, resectable non–small cell lung cancer
T2 - A systematic review and meta-analysis
AU - Wu, Yajing
AU - Verma, Vivek
AU - Gay, Carl M.
AU - Chen, Yujia
AU - Liang, Fei
AU - Lin, Qiang
AU - Wang, Jianing
AU - Zhang, Wei
AU - Hui, Zhouguang
AU - Zhao, Min
AU - Wang, Jun
AU - Chang, Joe Y.
N1 - Publisher Copyright:
© 2023 American Cancer Society.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Background: Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes. Methods: Eligibility was resectable stage I–III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte–associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel–Haenszel fixed-effect or random-effect model was used, depending on the heterogeneity (I2). Results: Sixty-six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49–12.97; p <.001), progression-free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38–0.67; p <.001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36–0.74; p =.0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67–1.52; p =.97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15–0.43; p <.001) and OS (HR, 0.26; 95% CI, 0.10–0.67; p =.005). PD-L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22–7.03; p =.02). Conclusions: In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD-L1, without increasing toxicities. Plain Language Summary: This meta-analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non-small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand-1, without increasing toxicities.
AB - Background: Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes. Methods: Eligibility was resectable stage I–III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte–associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel–Haenszel fixed-effect or random-effect model was used, depending on the heterogeneity (I2). Results: Sixty-six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49–12.97; p <.001), progression-free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38–0.67; p <.001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36–0.74; p =.0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67–1.52; p =.97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15–0.43; p <.001) and OS (HR, 0.26; 95% CI, 0.10–0.67; p =.005). PD-L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22–7.03; p =.02). Conclusions: In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD-L1, without increasing toxicities. Plain Language Summary: This meta-analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non-small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand-1, without increasing toxicities.
KW - immunotherapy
KW - neoadjuvant
KW - non-small cell lung cancer
KW - pathologic response
KW - survival
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U2 - 10.1002/cncr.34755
DO - 10.1002/cncr.34755
M3 - Article
C2 - 36994945
AN - SCOPUS:85152085345
SN - 0008-543X
VL - 129
SP - 1969
EP - 1985
JO - Cancer
JF - Cancer
IS - 13
ER -