Immune-Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer With Uncommon Histology
Sara Manglaviti1, Marta Brambilla1, Diego Signorelli2
1Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Background:
Immune-checkpoint inhibitors (ICIs) have significantly improved outcome of advanced non-small cell lung cancer (aNSCLC) patients. However, their efficacy remains uncertain in uncommon histologies (UH).
Materials And Methods:
Data from ICI treated aNSCLC patients (April,2013-January,2021) in one Institution were retrospectively collected. Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox proportional hazards regression model, respectively. Objective response rate (ORR) and disease control rate (DCR) were assessed.
Results:
Of 375 patients, 79 (21.1%) had UH: 19 (24.1%) sarcomatoid carcinoma, 15 (19.0%) mucinous adenocarcinoma, 10 (12.6%) enteric adenocarcinoma, 8 (10.1%) adenocarcinoma not otherwise specified, 7 (8.9%) large-cell neuroendocrine carcinoma, 6 (7.6%) mixed histology non-adenosquamous, 5 (6.3%) adenosquamous carcinoma, 9 (11.4%) other UH. In UH group, programmed death-ligand 1 (PD-L1) <1%, 1-49%, ≥50% and unknown expression were reported in 27.8%, 22.8%, 31.7% and 17.7% patients respectively and ICI was the second/further-line in the majority of patients. After a median follow-up of 35.64 months (m), median progression-free survival (mPFS) was 2.5 m in UH [95% CI 2.2-2.9 m] versus (vs.) 2.7 m in CH [95% CI 2.3-3.2 m, P-value = .584]; median overall survival (mOS) was 8.8 m [95% CI 4.9-12.6 m] vs. 9.7 m [95% CI 8.0-11.3 m, P-value = .653]. At multivariate analyses only ECOG PS was a confirmed prognostic factor in UH. ORR and DCR were 25.3% and 40.5% in UH vs. 21.6% and 49.5% in CH [P-value = .493 and .155 respectively].
Conclusions:
No significant differences were detected between UH and CH groups. Prospective trials are needed to understand ICIs role in UH population.
Insights
Immune-checkpoint inhibitors (ICIs) show similar efficacy in advanced non-small cell lung cancer (aNSCLC) patients with uncommon histologies (UH) compared to common histologies (CH). Further prospective trials are necessary to confirm the role of ICIs in the UH population.
Area of Science:
- Oncology
- Immunotherapy
- Thoracic Surgery
Background:
- Immune-checkpoint inhibitors (ICIs) have transformed advanced non-small cell lung cancer (aNSCLC) treatment.
- Efficacy of ICIs in patients with uncommon histologies (UH) remains less understood compared to common histologies (CH).
Purpose of the Study:
- To evaluate the efficacy of ICIs in aNSCLC patients with UH.
- To compare outcomes of UH patients treated with ICIs against CH patients.
Main Methods:
- Retrospective analysis of ICI-treated aNSCLC patients from April 2013 to January 2021.
- Kaplan-Meier and Cox regression models for survival analyses (progression-free survival and overall survival).
- Assessment of objective response rate (ORR) and disease control rate (DCR).
Main Results:
- Of 375 patients, 79 (21.1%) had UH, including sarcomatoid carcinoma, mucinous adenocarcinoma, and others.
- No significant differences in median progression-free survival (2.5m vs 2.7m) or median overall survival (8.8m vs 9.7m) were observed between UH and CH groups.
- Objective response rate (25.3% vs 21.6%) and disease control rate (40.5% vs 49.5%) were comparable between UH and CH groups.
Conclusions:
- ICIs demonstrate comparable efficacy in aNSCLC patients with UH and CH.
- ECOG performance status was the only significant prognostic factor identified in the UH group.
- Prospective studies are essential to elucidate the precise role and optimal use of ICIs in the UH population.
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