Abstract
Squamous cell lung cancer (SqCLC) is the second most common histotype of non-small cell lung cancer (NSCLC) and is characterized by severe prognosis and lack of specific target agents. Atezolizumab is the first anti Programmed Death Ligand-1 (PDL-1) inhibitor approved for NSCLC patients of both histology in case of disease progression after first or further lines of therapy. Numerous studies are investigating the potential role of atezolizumab in different therapeutic setting, including SqCLC subtype. We searched for published clinical trials in Pubmed database, using the terms "atezolizumab", "squamous cell lung cancer", "NSCLC" and "non-small cell lung cancer". We also searched for recently concluded and not yet published or ongoing trials in clinicaltrials.gov and in data from the latest international congresses. The aim of this review is to summarize current evidence on atezolizumab in SqCLC, from first line setting to novel potential indications from ongoing trials. Strengths and weaknesses of atezolizumab treatment were highlighted to speculate the role of this immune checkpoint inhibitor in novel future clinical scenarios.
Highlights
Pembrolizumab, another anti PD-1 antibody (Ab), was evaluated in pretreated positive PDL1 patients, but not in Squamous cell lung cancer (SqCLC) [13]
In October 2016, based on the results of the OAK trial, atezolizumab was approved by the Food and Drug Administration (FDA) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progresses during or following a platinum-containing chemotherapy; the drug has been approved for this indication in many other countries
We tried to highlight the differences among atezolizumab and other immune-check point inhibitors (ICIs), considering the limitation of subgroup analysis in clinical trials non- restricted to SqCLC
Summary
In clinical trials the use of ICIs in first line setting is associated with greater efficacy than in second- or further lines, maybe because of a more effective immune system and a more limited disease burden. With a median followup of 25.5 months, mOS was not statistically different in the atezolizumab + carboplatin + nab-paclitaxel group compared to the chemotherapy group (14.2 vs 13.5 months, HR 0.88, 95% CI 0.72–1.05, p = 0.1581); a mOS improvement was observed in patients with high PD-L1 expression with atezolizumab + carboplatin + nab-paclitaxel (mOS 23.4 vs 10.2 months; HR 0.48 95% CI: 0.29, 0.81) [19] Due to these negative results, no further analyses will be done on arm A and arm C and differences in synergistic effects with anti-microtubule agents will not be examined. The IMpower 131 is a negative trial and its final results only suggest that patients with metastatic SqCLC and high tumor PD-L1 expression may potentially benefit from combining carboplatin + nab-paclitaxel with atezolizumab. Atezolizumab alone or in combination with chemotherapy in first line setting in sqCLC seems to improve outcome, but the final results of IMpower 110 and 131 trials on OS do not completely support its use in clinical practice
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