CoChat
Sign Up
Cited by 277Cancer Immunotherapy and BiomarkersLung Cancer Research StudiesLung Cancer Treatments and Mutations

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Sex-Based Heterogeneity in Response to Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis

Open access
Conforti, Fabio, Pala, Laura, Bagnardi, Vincenzo, Viale, Giuseppe, De Pas, Tommaso, Pagan, Eleonora, Pennacchioli, Elisabetta, Cocorocchio, Emilia, Ferrucci, Pier Francesco, De Marinis, Filippo, Gelber, Richard D, Goldhirsch, Aron·2019·JNCI: Journal of the National Cancer Institute
DOI 10.1093/jnci/djz094PMC PMC6695312
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: We previously showed that therapy with anti–checkpoints T-lymphocyte-associated protein 4 (anti–CTLA-4) or antiprogrammed cell death protein 1 (anti–PD-1) agents was more effective for men as compared with women. However, because the sex-dimorphism of the immune system is complex, involving multiple elements of immune responses, it is possible that women could derive larger benefit than men from strategies other than therapy with immune checkpoint inhibitors (ICIs) alone. Here we investigated whether women could derive larger benefit than men from the combination of chemotherapy and anti-PD-1 or anti-PD-L1. Methods: We performed two meta-analyses. The first included all randomized controlled trials (RCTs) testing anti-PD1 and anti–PD-L1 plus chemotherapy vs chemotherapy to assess different efficacy between men and women. The second included all RCTs of first-line systemic treatment in advanced non-small cell lung cancer testing anti–PD-1/PD-L1 given either alone or combined with chemotherapy to assess the different efficacy of these two immunotherapeutic strategies according to patients’ sex. For each RCT included in the two meta-analyses, first, a trial-specific ratio of hazard ratios (HRs) was calculated from the ratio of the reported hazard ratios in men and in women; second, these trial-specific ratios of hazard ratios were combined across trials using a random-effects model to obtain a pooled hazard ratios ratio. A pooled HRs ratio estimate lower than 1 indicates a greater treatment effect in men, and higher than 1 a greater effect in women. Results: Eight RCTs were included in the first meta-analysis. The pooled overall survival hazard ratios (OS-HRs) comparing anti–PD-1/PD-L1 plus chemotherapy vs chemotherapy was 0.76 (95% confidence interval [CI] = 0.66 to 0.87) for men and 0.48 (95% CI = 0.35 to 0.67) for women. The pooled ratio of the overall survival hazard ratios reported in men vs women was 1.56 (95% CI = 1.21 to 2.01), indicating a statistically significant greater effect for women. Six RCTs were included in the second meta-analysis: three tested an anti-PD-1 alone, whereas three RCTs tested anti-PD-1/PD-L1 plus chemotherapy. The pooled overall survival hazard ratios were 0.78 (95% CI = 0.60 to 1.00) in men and 0.97 (95% CI = 0.79 to 1.19) in women for anti–PD-1 alone, compared with 0.76 (95% CI = 0.64 to 0.91) in men and 0.44 (95% CI = 0.25 to 0.76) in women for anti–PD-1/PD-L1 plus chemotherapy. The pooled ratio of overall survival hazard ratios was 0.83 (95% CI = 0.65 to 1.06) for anti–PD-1 alone, indicating a greater effect in men, and 1.70 (95% CI = 1.16 to 2.49) for anti–PD-1/PD-L1 plus chemotherapy, indicating a greater effect in women. Conclusion: Women with advanced lung cancer derived a statistically significantly larger benefit from the addition of chemotherapy to anti–PD-1/PD-L1 as compared with men.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/jnci/djz094

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Cited by

Sorted by citations

See all 277

Related

See all

Metadata

Authors
Conforti, F., Pala, L., Bagnardi, V., Viale, G., De Pas, T., Pagan, E., Pennacchioli, E., Cocorocchio, E., Ferrucci, P. F., De Marinis, F., Gelber, R. D., & Goldhirsch, A.
Affiliations
See the Notes section for the full list of authors’ affiliations
Corresponding author
Conforti, Fabio
ORCID
Venue
JNCI: Journal of the National Cancer Institute
Publisher
Oxford University Press (OUP)
Published
2019-05-20
Volume
111
Issue
8
Pages
772-781
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
DOI
10.1093/jnci/djz094
PMC
PMC6695312
OpenAlex
W2946644285
Cited by
262
References
34
Citations by year
2026: 23 · 2025: 39 · 2024: 56 · 2023: 36 · 2022: 36 · 2021: 39 · 2020: 28 · 2019: 4
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • JNCI Journal of the National Cancer Institute (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
sex differences, lung cancer immunotherapy, immune checkpoint inhibitors, anti-PD-1, PD-L1 inhibitors, anti-CTLA-4, non-small cell lung cancer, combination chemotherapy, overall survival, first-line systemic treatment
MeSH terms
Female, Humans, Immunotherapy, Lung Neoplasms, Male, Sex Characteristics, Disease-Free Survival, B7-H1 Antigen, CTLA-4 Antigen, Programmed Cell Death 1 Receptor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review