Bruna Pellini/LinkedIn
Jun 12, 2025, 18:22
Bruna Pellini: Chemotherapy Plus Anti-PD-1 or Anti-PD-L1 in Advanced PD-L1-Negative sqNSCLC
Bruna Pellini, Assistant Professor at the University of South Florida and Assistant Member of the Department of Thoracic Oncology at Moffitt Cancer Center, shared a post on X about a paper she co-authored with colleagues published in Clinical Lung Cancer:
“New in Clinical Lung Cancer. Can chemo and anti–PD-(L)1 improve outcomes in PD-L1–negative squamous NSCLC?
Our team conducted a meta-analysis of 11 phase III RCTs (n=1548) – the largest to date! Led by stellar IM resident Nicolas Peruzzo.
PD-L1 <1% NSCLC patients often have limited benefit from immunotherapy.
Clinical trials show mixed signals in this population.
Guidelines remain hesitant.
We aimed to bring clarity.
Meta-analysis included 11 global phase III trials:
KEYNOTE-407
CheckMate 227
ASTRUM-004
EMPOWER-Lung 3
CameL-Sq
…and more
All compared chemo + anti–PD-(L)1 vs chemo (± placebo) in PD-L1 <1% sqNSCLC.
ORR improved 36% with chemo + anti–PD-(L)1
Risk Ratio = 1.36 [95% CI, 1.16–1.60]
p = .0001
Low heterogeneity (I² = 24%)
First signal of consistent tumor response benefit in this PD-L1–negative population!
PFS improved by 42%!
Hazard Ratio = 0.58 [95% CI, 0.48–0.69]
p < .00001
Note: Some inter-study heterogeneity observed.
Subgroup analysis:
Liver mets drive PFS heterogeneity.
Split analysis by prevalence of liver metastases (≥15% vs <15%) shows:
PFS benefits clearly when fewer patients have liver mets.
OS also improved:
HR = 0.81 [95% CI, 0.69–0.96], p = .02
This supports chemo + anti–PD-(L)1 as a legit standard-of-care option in 1L PD-L1–negative sqNSCLC.
Our findings reinforce:
Even in PD-L1–negative SCC of the lung, ICI+chemo can yield clinically meaningful survival gains.
Sets benchmark for comparison with dual ICI regimens (e.g., CheckMate 227, 9LA).
What’s next?
We need head-to-head RCTs of:
anti–PD-(L)1 + chemo vs
anti–PD-1 + anti–CTLA-4 (± chemo)
Especially important for liver mets and genomically enriched subsets (e.g., STK11, KEAP1).
A huge shoutout to the amazing multi-institutional team: Nicolas Peruzzo, Andres F. Cardona, Joshua Reuss, Marcelo Corassa, and many global collaborators!
Take-home points:
In PD-L1–negative advanced squamous NSCLC:
Chemo + anti–PD-(L)1 improves ORR, PFS, and OS
Consider liver mets in prognostic stratification
Supports ICI + chemo as frontline standard.”
Title: Chemotherapy Plus Anti-PD-1 or Anti-PD-L1 in Advanced PD-L1–Negative Squamous Cell Lung Carcinoma: A Systematic Review and Meta-Analysis
Authors: Nicolas Peruzzo, Gabriel Lenz, Ted Akhiwu, Mariah Bilalaga, Greeshma Nihitha Gaddipati, Nathalia Luisy Farias Müller, Loren Zarpellon, Fernando Venero, Marcelo Corassa, Andrés F. Cardona, Joshua E. Reuss, Bruna Pellini
You can read the Full Article in Clinical Lung Cancer.
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