Chemo Doesn’t Improve Lung Adenocarcinoma Survival in Most

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The study covered in this summary was published on medrxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Adding chemotherapy to programmed cell death protein 1/programmed cell death-ligand 1 [PD-(L)1] blockade for first-line treatment of advanced lung adenocarcinomas increases the likelihood of response but ultimately improves survival only among patients with high PD-L1 expression (≥ 50%) who never smoked.

Why This Matters

  • PD-(L)1 blockers alone and in combination with chemotherapy are both indicated for first-line treatment of advanced lung adenocarcinomas with 1% or higher PD-L1 expression.

  • However, the two approaches have never been compared prospectively to identify groups who benefit from one approach over the other, making treatment decisions difficult.

  • The current study addressed this gap, finding that combination therapy should be strongly considered for never-smokers even in the presence of high tumor mutation burdens and/or PD-L1 expression.

  • For other patients, better objective response rates (ORR) and progression free survival (PFS) with combination therapy did not seem to translate to longer overall survival (OS).

Study Design

  • The study included 874 patients with advanced lung adenocarcinoma who had tumor PD-L1 expressions of at least 1%, no targetable EGFR or ALK alterations, and were treated in the first line from 2011 to 2020.

  • Overall, 55% of patients received PD-(L)1 blockers alone, and the rest were treated with PD-(L)1 blockers plus chemotherapy.

  • The team used propensity-adjusted analyses to control for baseline differences between the two treatment groups.

  • Median follow-up was 23 months.

Key Results

  • Overall, the combination treatment was associated with improved ORR (44% vs 35%) and PFS (median 6.9 vs 4.9 months).

  • Patients with very high PD-L1 expression (≥ 90%) were the only group who showed no initial benefit from combination therapy.

  • However, there was no OS benefit with combination therapy across the entire study population (median 17 vs 20 months with PD-(L)1 blockade alone, P = .50).

  • On propensity-adjusted analyses, only never-smokers with PD-L1 expressions of 50% or higher had an OS benefit from combination therapy (hazard ratio, 2.98; P = .034).

  • There was no clinical benefit of adding chemotherapy to PD-(L)1 blockers in patients with liver or brain metastases.

Limitations

  • It was a retrospective study.

  • The power of the analysis was limited for patients with PD-L1 expressions of 1%-49% due to modest sample size.

Disclosures

  • The work was funded by the National Institutes of Health and others.

  • Investigators reported ties to AstraZeneca, Merck, Sanofi, and many other companies.

This is a summary of a preprint research study, “Efficacy of PD-(L)1 Blockade Monotherapy Compared to PD-(L)1 Blockade plus Chemotherapy in First-Line PD-L1-Positive Advanced Lung Adenocarcinomas: A Cohort Study,” led by Arielle Elkrief of the Memorial Sloan Kettering Cancer Center, New York City, provided to you by Medscape. The study has not been peer reviewed. The full text can be found at medrxiv.org.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who has worked for several major news outlets before joining Medscape and also an MIT Knight Science Journalism fellow. Email: [email protected].

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