Squamous cell lung cancer, often occurring in the central part of the lung or the main airway, is more strongly associated with smoking than any other type of non-small cell lung cancer. 

Reference

Sabbula BR et al. 2023. Available at: www.pubmed.ncbi.nlm.nih.gov/33232091/ (accessed 4 December 2023).

Irrespective of histology, targeted therapies are the main choice of treatment in patients with lung cancer with an actionable molecular target mutation.¹ Both ESMO and NCCN guidelines recommend immunotherapy-based regimens for patients with SCC that is positive for PD-L1 expression.^2,3 NCCN guidelines recommend molecular testing for actionable biomarkers in all patients with metastatic NSCLC irrespective of histology, when clinically feasible.² ESMO guidelines recommend molecular testing for actionable molecular targets in SCC only if the patient is a never or former light smoker (<15 pack years), a long-time ex-smoker, or <50 years old.³ However, targeted therapeutic options for SCC are limited, because of the lack of actionable genomic targets.⁴  

Abbreviations

ESMO, European Society of Medical Oncology; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; SCC, squamous cell lung cancer.

References

1. Xiao Y, et al. Front Pharamcol. 2023;14:11255547.
2. NCCN. Non-small cell lung cancer. V5.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 28 November 2023).
3. Hendriks LE, et al. Ann Oncol. 2023;34:358–76.
4. Satpathy S, et al. Cell. 2021;184:4348–71.

ESMO and NCCN guidelines recommend monotherapy with an ICI (atezolizumab, cemiplimab or pembrolizumab) as the preferred options for patients with squamous cell lung cancer with PD-L1 ≥ 50% and a performance score of 0–2.^1,2 Immunotherapy in combination with chemotherapy is recommended by the NCCN guidelines for patients with PD-L1 level between 1 and <50% and for patients with performance score of 0–1 and any level PD-L1 expression level by the ESMO guidelines.^1,2

Abbreviations

ESMO, European Society of Medical Oncology; ICI, immune checkpoint inhibitor; NCCN, National Comprehensive Cancer Network; PD-L1, programmed death-ligand 1. 

References

1. NCCN. Non-small cell lung cancer. V5.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 28 November 2023).
2. Hendriks LE, et al. Ann Oncol. 2023;34:358–76.

As part of management of immunotherapy related toxicities, NCCN guidelines recommend counselling patients and caregivers on the warning signs and symptoms of immune-related AEs prior to initiating immunotherapy.¹ The most common grade 3 to 5 immune-related AEs in patients receiving immunotherapy involve the gastrointestinal tract.² Atezolizumab, cemiplimab and pembrolizumab, which are ICIs recommended as monotherapy for squamous cell lung cancer in some patients, are not contraindicated in patients with a history of colitis or other comorbidities.^3,4 Dose reductions are not recommended with any of these ICIs, and gastrointestinal side effects can usually be managed by withholding immunotherapy until the symptoms subside or permanently discontinuing treatment in the case of grade 4 AEs.^2–4

Abbreviations

AE, adverse event; ICI, immune checkpoint inhibitor; NCCN, National Comprehensive Cancer Network.

References

1. NCCN. Management of immunotherapy-related toxicities. V1.2024. Available at: www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf (accessed 12 December 2023).
2. Capello G, et al. BJR Open. 2021;3:20210027.
3. EMA. Available at: www.ema.europa.eu/en/medicines; SmPCs searchable by drug name (accessed 11 December 2023).
4. FDA. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm; PIs searchable by drug name (accessed 11 December 2023).

An exploratory subgroup analysis of patients with squamous cell lung cancer (without EGFR, ALK or ROS1 aberrations) treated with cemiplimab was performed using data from the EMPOWER-Lung 1 and 3 phase III clinical trials. The analysis demonstrated improved clinical benefit (overall survival) in patients with PD-L1 expression ≥50% treated with cemiplimab monotherapy (EMPOWER-Lung 1) and in patients treated with cemiplimab plus chemotherapy regardless of PD-L1 expression levels (EMPOWER-Lung 3), compared to chemotherapy alone. 

Abbreviations

ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; PD-L1, programmed death-ligand 1; ROS1, c-ros oncogene 1 receptor tyrosine kinase.

Reference

Makharadze T, et al. Ann Oncol. 2023;34(Suppl. 2):S818.