Age does matter in adolescents and young adults vs. older adults with lung adenocarcinoma: A retrospective analysis comparing clinical characteristics and outcomes in response to systematic treatments

Adenocarcinoma is the most common histological type of lung cancer in adolescents and young adults (AYAs; ˂50 years of age). However, few clinical trials that have investigated systematic treatments regard AYAs as a special cohort, and the differences in progression-free survival (PFS) and overall survival (OS) between AYAs and older adults is still unclear. The present study compared clinical characteristics, targetable genomic mutations, toxicity, efficacy and prognostic response to systematic treatments in AYAs (n=251) and older adults (n=1,098) who were diagnosed with lung adenocarcinoma between January 2013 and December 2017 at YueBei People's Hospital (Shaoguan, China). Compared with older adults, AYAs with lung adenocarcinoma were more frequently female and non-smokers, with a higher ratio of patients receiving chemotherapy and targeted therapy, and fewer untreated. More AYAs harbored targetable genomic mutations, including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations, while more older adults harbored KRAS proto-oncogene GTPase mutations. EGFR L858R was significantly more prevalent among older adults, while 19Del was common in AYAs. AYAs showed a higher objective response rate (ORR) and a lower grade 3–4 treatment-related adverse event (TRAE) percentage following systematic chemotherapy, but shared a similar ORR and grade 3–4 TRAE percentage with older adults following targeted therapies. AYAs experienced a shorter progression-free survival time following EGFR-tyrosine kinase inhibitor (TKI) treatment due to the higher number of metastatic organs at the time of the initial cancer diagnosis. However, there was a survival advantage of AYAs over older adults in terms of the response to systemic chemotherapy, and an age of ˂50 years was indicated as one of the positive predictors for OS time. Overall, AYAs with lung adenocarcinoma harbored distinctive clinical and genomic characteristics, and exhibited PFS and OS disadvantages following first-line EGFR-TKIs and advantages following systematic chemotherapy. However, the age-related difference in prognosis existed solely in patients who received systematic chemotherapy.