Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations

Abstract

Introduction The efficacy of targeted therapies in oncogene-driven lung adenocarcinomas (LUADs) has been well established; however, the benefit for EGFR -mutant or ALK -rearranged lung squamous cell carcinomas (LUSCs) is less known, partially owing to the rarity of the incidence. Methods We reviewed the database of the MD Anderson Cancer Center and identified metastatic LUSC with classic EGFR or ALK alterations. Results There were eight patients with EGFR -mutant LUSC (median age = 58 y) and six patients with EML4-ALK LUSC (median age = 50 y) who received tyrosine kinase inhibitors (TKIs) that were identified. Of the 14 patients, 11 (79%) were females and 12 (86%) were never smokers, similar to the demographics of EGFR or ALK LUAD. With TKI treatment, seven of eight cases of EGFR LUSC and four of six cases of ALK LUSC achieved partial response or stable disease, but the progression-free survival was 4.9 months and 2.9 months for EGFR -mutant and ALK -rearranged LUSC, respectively. In addition, we compared comutation profile of EGFR -mutant LUAD (The Cancer Genome Atlas, n = 46) versus LUSC (n = 19) and found that the comutation patterns are more consistent with squamous disease with a higher incidence of PIK3CA ( p = 0.02) and KRAS or BRAF ( p = 0.04) alterations. Conclusions EGFR or ALK alterations occur in patients with LUSC, especially never-smoker females. TKI treatments render clinical benefit in disease control, but the duration was considerably truncated compared with those historically observed in LUAD.

EGFR mutations and high PD-L1 expression of lung squamous cell carcinoma patients achieving pCR following neoadjuvant immuno-chemotherapy: Case report

“…EGFR or ALK gene alterations occur in patients with LUSC, especially non-smoking females, in which TKI treatments present clinical benefits in disease control with a considerably shorter drug-resistant duration in LUSC patients than in lung adenocarcinoma (LUAD) patients ( 9 ). A previous study ( 10 ) reported that the first-line pembrolizumab treatment was superior to conventional chemotherapy for lung cancer patients with high PD-L1 expression, and the subgroup analysis showed that pembrolizumab was more effective in treating LUSC than non-LUSC.…”

Treatment Considerations for Patients With Advanced Squamous Cell Carcinoma of the Lung

“…33 ALK mutations are considered even rarer and have only been described in case studies. 34 Nevertheless, a recent retrospective analysis indicated that TKIs can render clinical benefit in SCC patients with targetable mutations. 34 In 8 patients with EGFR mutations, TKIs (osimertinib or erlotinib) conferred a disease control rate (DCR) of 88%.…”

“…34 Nevertheless, a recent retrospective analysis indicated that TKIs can render clinical benefit in SCC patients with targetable mutations. 34 In 8 patients with EGFR mutations, TKIs (osimertinib or erlotinib) conferred a disease control rate (DCR) of 88%. In 4 patients with ALK mutations, TKIs were associated with a DCR of 67%.…”

Genetic Clonality as the Hallmark Driving Evolution of Non-Small Cell Lung Cancer

“…On the other hand, many driver alterations in NSCLC are considered ‘druggable’, and the development of agents targeting them has revolutionized the management of NSCLC treatment [ 30 , 48 , 83 ]. In particular, in genetically selected LUAD patients, molecularly targeted therapies provide significant superiority over standard platinum-based chemotherapy, and there are attempts to obtain similar results in LUSC [ 30 , 84 ]. In Table 2 we summarized the common driver alterations associated with LUAD and LUSC, indicating their frequency in TCGA (The Cancer Genome Atlas) database, as well as matching them with a potential clinical trial.…”