Sex difference in survival benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer: A meta-analysis.
Tingting Liu, Dandan Song, Jun Chen et al.
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In 30 seconds
This random-effects meta-analysis examined sex-stratified survival outcomes from 42 phase 3 randomised trials comparing immune checkpoint inhibitors (ICIs) with chemotherapy in advanced non-small cell lung cancer. Across 25,827 participants, ICIs improved overall and progression-free survival in both males and females. Treatment-by-sex analyses found greater relative benefit in males for overall survival (interaction HR = 0.90 [95% CI 0.84-0.97]; P = 0.01) and progression-free survival (interaction HR = 0.82 [95% CI 0.73-0.92]; P = 0.0006). The progression-free survival difference persisted in ICI monotherapy subgroups after false discovery rate correction, but not with ICI plus chemotherapy.
Key findings
- Compared with chemotherapy, ICIs improved overall survival in males (HR 0.74 [95% CI 0.71-0.78]) and females (HR 0.83 [95% CI 0.77-0.90]).
- ICIs improved progression-free survival in males (HR 0.59 [95% CI 0.54-0.64]) and females (HR 0.76 [95% CI 0.66-0.86]).
- Sex-based progression-free survival differences remained significant after FDR correction for ICI monotherapy (adjusted P = 0.001), anti-PD-1 monotherapy (adjusted P = 0.001), and PD-L1 ≥ 50% (adjusted P = 0.004).
- No significant sex-based differences in overall or progression-free survival were observed with ICI plus chemotherapy.
Why it matters
The findings suggest that relative survival benefit from ICIs may vary by sex, particularly for progression-free survival with ICI monotherapy. This may inform interpretation of trial results and highlights the value of reporting sex-stratified outcomes. The results do not establish why the differences occur or whether they should guide treatment selection.
What to keep in mind
The authors note baseline confounder imbalances and underrepresentation of females in the included trials; the findings require confirmation in trials designed to assess sex-based differences.