EGFR L861Q and CDK4 amplification responding to afatinib combined with palbociclib treatment in a patient with advanced lung squamous cell carcinoma

Patients with mutations in EGFR, which is identified as a crucial driver gene of non-small cell lung cancer (NSCLC), may benefit from EGFR-TKI in cancer treatment [ [1] Furuyama K. Harada T. Iwama E. Shiraishi Y. Okamura K. Ijichi K. Fujii A. Ota K. Wang S. Li H. Sensitivity and kinase activity of epidermal growth factor receptor (EGFR) exon 19 and others to EGFR‐tyrosine kinase inhibitors. Cancer Sci. 2013; 104: 584-589 Crossref PubMed Scopus (41) Google Scholar ]. Afatinib shows better activity than other EGFR-TKI for patients with NSCLC harboring the uncommon mutation EGFR L861Q [ [2] Yang J.C. Sequist L.V. Geater S.L. Tsai C.M. Mok T.S.K. Schuler M. Yamamoto N. Yu C.J. Ou S.H.I. Zhou C. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015; 16: 830-838 Abstract Full Text Full Text PDF PubMed Scopus (597) Google Scholar ]. Nevertheless, the presence of co-mutations may affect the efficacy of TKI, such as mutations in CDK4 [ [3] Blakely C.M. Watkins T.B. Wu W. Gini B. Chabon J.J. McCoach C.E. McGranahan N. Wilson G.A. Birkbak N.J. Olivas V.R. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat. Genet. 2017; 49: 1693 Crossref PubMed Scopus (297) Google Scholar ]. A previous preclinical study showed the combination of afatinib and palbocicib, the inhibitor of CDK4, could be a promising strategy to reverse acquired resistance in NSCLC [ [4] Nie H. Zhou X. Shuzhang D. Nie C. Zhang X. Huang J. Palbociclib overcomes afatinib resistance in non-small cell lung cancer. Biomed. Pharmacother. 2019; 109: 1750-1757 Crossref PubMed Scopus (7) Google Scholar ]. However, the treatment scheme has not been reported yet in clinical application. Herein, we report for the first time the benefits of afatinib combined with palbociclib for a patient with advanced lung squamous cell carcinoma (LUSC) harboring EGFR L861Q and CDK4 amplification.