Smoke detector.

Top Line: Have you ever wanted an RTOG 0129-style risk stratification for lung cancer?
The Study: This novel retrospective study looks at the influence of smoking status on the prognostic power of PD-L1 expression. Among 315 patients with non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50% treated with upfront immune checkpoint inhibitor (ICI) monotherapy across five academic institutions, 75% were heavy smokers (>10 pack-years), 13% were light smokers (≤10 pack years) and the other 11% were “never” smokers (ok, if you pressed them they admitted to "at most" 100 cigarettes ever). Now, here’s where the results may surprise you. The objective response rate was 40% among heavy or light smokers versus only about one quarter of never smokers. What’s more, the median durations of response were 18 (heavy), 11 (light) and 7 (never) months. Finally, median progression-free survival followed a similar trend with a median of >5, 4, and 3 months, respectively. Interestingly (and news to us) this is in-line with subgroup analyses of larger randomized trials, such as KEYNOTE-042 that demonstrated no improvement in overall survival with pembro among never smokers, even those with PD-L1 expression >50%.
TBL: Smoking status may need to be factored into the decision on when to add chemo for NSCLC with higher PD-L1 expression, as never smokers appear to derive less of a benefit from ICI monotherapy. | Gainor, Ann Oncol 2020

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