The treatment of patients with non-small cell lung cancer carrying uncommon mutations, mutations, or brain metastases: a systematic review of pre-clinical and clinical findings for dacomitinib.

Background: Accumulating evidence has shown that dacomitinib has potential activities for patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor () mutations, human epidermal growth factor receptor 2 () mutations, or central nervous system (CNS) metastases.

Methods: This study aimed to give a systematic review on its potential applications in the above settings by searching MEDLINE/PubMed, Embase, Cochrane Library, American Society of Clinical Oncology.org, European Society for Medical Oncology.org, and ClinicalTrials.gov.

Results: The literature search yielded 649 publications in total. According to our findings, dacomitinib exhibited promising efficacy in patients with major uncommon mutations (including G719X, S768I, and L861Q). Both exon 20 insertional mutation (Ex20ins) and Ex20ins demonstrated significant internal heterogeneity in response to dacomitinib, among which specific subtypes (including D770delinsGY, A763_Y764insFQEA, and M774delinsWLV) were highly sensitive. Other uncommon mutations including 18del and L747P have also been shown responsive to dacomitinib. Interestingly, limited studies suggested dacomitinib application on certain first or third generation tyrosine kinase inhibitors (TKIs)' resistant secondary mutations. Last but not least, both pre-clinical and clinical data indicated that dacomitinib has an encouraging intracranial tumor control ability, regardless of uncommon mutations.

Conclusions: Dacomitinib demonstrated good disease control on patients with NSCLC harboring major uncommon mutations and specific or mutation subtypes, and selective clinical application of dacomitinib is considerable in this setting, especially for those with intracranial metastases.