Efficacy of PD-(L)1 blockade monotherapy compared with PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: A cohort study Journal Article
| Authors: | Elkrief, A.; Alessi, J. M. V.; Ricciuti, B.; Brown, S.; Rizvi, H.; Preeshagul, I. R.; Wang, X.; Pecci, F.; Di Federico, A.; Lamberti, G.; Egger, J. V.; Chaft, J. E.; Rudin, C. M.; Riely, G. J.; Kris, M. G.; Ladanyi, M.; Chen, Y.; Hellmann, M. D.; Shen, R.; Awad, M. M.; Schoenfeld, A. J. |
| Article Title: | Efficacy of PD-(L)1 blockade monotherapy compared with PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: A cohort study |
| Abstract: | Background Single-agent PD-(L)1 blockade (IO) alone or in combination with chemotherapy (Chemotherapy-IO) is approved first-line therapies in patients with advanced lung adenocarcinomas (LUADs) with PD-L1 expression ≥1%. These regimens have not been compared prospectively. The primary objective was to compare first-line efficacies of single-agent IO to Chemotherapy-IO in patients with advanced LUADs. Secondary objectives were to explore if clinical, pathological, and genomic features were associated with differential response to Chemotherapy-IO versus IO. Methods This was a multicenter retrospective cohort study. Inclusion criteria were patients with advanced LUADs with tumor PD-L1 ≥1% treated with first-line Chemotherapy-IO or IO. To compare the first-line efficacies of single-agent IO to Chemotherapy-IO, we conducted inverse probability weighted Cox proportional hazards models using estimated propensity scores. Results The cohort analyzed included 866 patients. Relative to IO, Chemotherapy-IO was associated with improved objective response rate (ORR) (44% vs 35%, p=0.007) and progression-free survival (PFS) in patients with tumor PD-L1≥1% (HR 0.84, 95% CI 0.72 to 0.97, p=0.021) or PD-L1≥50% (ORR 55% vs 38%, p<0.001; PFS HR 0.68, 95% CI 0.53 to 0.87, p=0.002). Using propensity-adjusted analyses, only never-smokers in the PD-L1≥50% subgroup derived a differential survival benefit from Chemotherapy-IO vs IO (p=0.013). Among patients with very high tumor PD-L1 expression (≥90%), there were no differences in outcome between treatment groups. No genomic factors conferred differential survival benefit to Chemotherapy-IO versus IO. Conclusions While the addition of chemotherapy to PD-(L)1 blockade increases the probability of initial response, never-smokers with tumor PD-L1≥50% comprise the only population identified that derived an apparent survival benefit with treatment intensification. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
| Keywords: | adult; protein expression; treatment response; aged; middle aged; retrospective studies; gene mutation; major clinical study; overall survival; sequence analysis; clinical trial; monotherapy; combined modality therapy; follow up; progression free survival; cohort studies; gene expression; lung neoplasms; cohort analysis; retrospective study; protein p53; carcinogenesis; lung tumor; liver metastasis; lung adenocarcinoma; multicenter study; brain metastasis; non-small cell lung cancer; genetic marker; genetic markers; programmed death 1 ligand 1; comparative effectiveness; adenocarcinoma of lung; protein kinase lkb1; overall response rate; brg1 protein; humans; human; male; female; article; immune checkpoint inhibitors; b7-h1 antigen; doublet chemotherapy |
| Journal Title: | Journal for ImmunoTherapy of Cancer |
| Volume: | 11 |
| Issue: | 7 |
| ISSN: | 2051-1426 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2023-07-01 |
| Start Page: | e006994 |
| Language: | English |
| DOI: | 10.1136/jitc-2023-006994 |
| PUBMED: | 37487667 |
| PROVIDER: | scopus |
| PMCID: | PMC10373730 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Adam Schoenfeld --Source: Scopus |
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