Comparison of the efficacies of first-generation epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in patients with advanced non-small-cell lung cancer harboring EGFR mutations

Abstract Background Compared with standard chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, data comparing the efficacies of different EGFR−TKIs, especially regarding the presence of brain metastasis, are lacking. Methods EGFR-TKI naive patients with recurrent or stage IIIB/IV NSCLC harboring EGFR mutations, excluding resistance mutations, were enrolled in this study. We retrospectively determined progression-free survival (PFS) using the Kaplan−Meier method with log-rank test in patients treated with either gefitinib or erlotinib, cumulative incidence of central nervous system (CNS) progression using the Fine and Gray competing risk regression model, and favorable prognostic factors for CNS progression by multivariate analysis. Results Seventy-seven EGFR-TKI-naive patients were started on either gefitinib (n = 55) or erlotinib (n = 22) in our hospital from April 2010 to April 2016. Among the patients with brain metastasis, PFS tended to be longer in the erlotinib than in the gefitinib group. In the analysis of cumulative incidence, the probability of CNS progression was lower in the erlotinib group than in the gefitinib group. Particularly, in a subgroup analysis of the patients with brain metastasis, there was a significant difference between the erlotinib and gefitinib groups (hazard ratio 0.25; 95% confidence interval, 0.08–0.81; p = 0.021). Of the prognostic factors for CNS progression evaluated, the absence of brain metastasis before EGFR-TKI therapy and receiving erlotinib (vs gefitinib) had a significantly favorable effect on patient prognosis. Conclusion Although this was a retrospective analysis involving a small sample size, erlotinib is potentially more promising than gefitinib for treatment of brain metastasis in patients with EGFR-mutant NSCLC

Prospective evaluation of the G8 screening tool for prognostication of survival in elderly patients with lung cancer: A single-institution study.

The G8 questionnaire is a quick and easy-to-use screening tool. Several studies reported that the G8 questionnaire had a high sensitivity for predicting abnormalities in the full comprehensive geriatric assessment and predicted functional decline and survival in elderly cancer patients. The present study aimed to evaluate the role of the G8 questionnaire for predicting clinical outcomes and overall survival (OS) in elderly patients with lung cancer, who received chemotherapy or chemoradiotherapy. The data of 101 lung cancer patients aged ≥70 years, who were hospitalized between September 2011 and August 2014, were analyzed. Of these patients (median age, 77 years), 83 (82%) had impaired G8 scores. The proportion of patients with an impaired G8 score was significantly higher in patients aged ≥80 years than those aged <80 years (p = 0.04). All 18 patients with a normal G8 score possessed an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and none of the patients with a normal G8 score had an ECOG PS of ≥2 (p < 0.0001). An impaired G8 score tended to correlate with a relative dose intensity of <0.65 in patients who received chemotherapy or chemoradiotherapy (p = 0.05, odds ratio = 5.40). In the univariate analysis, an ECOG PS of ≥2 and an impaired G8 score were significantly associated with a poor OS (p = 0.009 and p = 0.003, respectively). Moreover, in the multivariate analysis, an ECOG PS of ≥2 (HR 2.55; 95% CI, 1.23-5.30; p = 0.01) and an impaired G8 score (HR 3.86; 95% CI, 1.44-13.36; p = 0.006) were remained independent prognostic factor for OS. G8 screening tool is useful for the prognostication of elderly lung cancer patients treated with chemotherapy. These finding suggest that the G8 questionnaire could be a useful tool in treatment decision-making to predict prognosis and prevent patients from receiving inappropriate anti-cancer treatment near the end of life

Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC

Abstract Background The relationship between epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance, including osimertinib, and programmed cell death‐ligand 1 (PD‐L1) expression status in EGFR‐mutated non‐small cell lung carcinoma (NSCLC) remains unclear. Patients and Methods We retrospectively analyzed 64 patients with unresectable advanced or metastatic NSCLC carrying EGFR exon 19 deletions (ex19del) or EGFR exon 21 L858R substitutions (L858R) who received osimertinib as the first‐line treatment. We compared progression‐free survival (PFS) between eligible patients with PD‐L1 tumor proportion scores (TPS) ≥20% and PD‐L1 TPS <20% using the Kaplan–Meier survival plots with a log‐rank test. Multivariate analysis was performed to examine the poor prognostic factors of PFS. Results The PD‐L1 TPS ≥20% group included 22 cases (median [range] age: 70.5 [33–86] years; 10 women [45.5%]; 11 current or ex‐smokers [50%]); ECOG performance status (PS) of 0–1/2/3/4 was noted in 16/4/1/1 patients, respectively. The PD‐L1 TPS <20% group included 42 patients (median [range] age 73 [43–88] years; 29 women [69%]; 12 current or ex‐smokers [28.6%]); ECOG PS of 0–1/2/3/4 was noted in 33/6/3/0 cases, respectively. The median PFS was 9.1 and 28.1 months in the PD‐L1 TPS ≥20% and PD‐L1 TPS <20% groups, respectively (log‐rank p = 0.013). Multivariate analysis revealed that PD‐L1 TPS ≥20% was associated with PFS (hazard ratio: 2.35, 95% confidence interval: 1.09–5.08, p = 0.030). Conclusion PD‐L1 TPS ≥20% in patients with EGFR‐mutated NSCLC may be associated with early resistance to osimertinib