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Background:> In an open-label, Phase III randomized study, gefitinib was found to be superior to pemetrexed-platinum in terms of progression-free survival in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. In this analysis, we have assessed the efficacy of gefitinib over pemetrexed-platinum using quality-adjusted time without symptoms or toxicity (Q-TWiST) of treatment analysis method. Methods: The overall survival in each arm was partitioned into the following three health states: time spent in Grade 2 or above toxicity after randomization and before progression (TOX state), time spent after randomization and before progression without Grade 2 or above toxicity (TWiST state), and time spent after progression (REL state). The mean Q-TWiST was calculated for each arm using utility coefficients of 0.65 for TOX, 0.71 for TWiST, and 0.67 for REL states. The difference in Q-TWiST and the 95% confidence interval (CI) of the difference were calculated using a nonparametric bootstrap.P= 0.05 was considered statistically significant. Results: The mean TOX duration (37.6 vs. 16.2 days,P < 0.001) and TWiST duration (211.7 vs. 162.2 days, P = 0.002) were higher in the gefitinib arm. The mean REL state duration was higher in the pemetrexed-carboplatin arm (164.4 vs. 74.3 days,P < 0.001). The mean Q-TWiST was 224.6 days in the gefitinib arm versus 235.9 days in the pemetrexed-carboplatin arm. The difference was 11.3 days; 95% CI, 6.920–29.564,P= 0.224. Conclusion: The mean Q-TWiST of patients in the gefitinib arm was similar to that of patients in the pemetrexed-carboplatin arm. These results challenge the superiority of sequencing gefitinib followed by chemotherapy over pemetrexed-carboplatin followed by gefitinib in terms of Q-TWiST.

Summary: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has exhibited efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a fatal adverse event of osimertinib treatment, and it requires treatment discontinuation. There are few reports regarding the safety and efficacy of osimertinib re-challenge in patients who experienced osimertinib-induced ILD. This retrospective study assessed this treatment option. We retrospectively collected data for patients treated with osimertinib who developed ILD at Shizuoka Cancer Center from April 2016 to March 2020. ILD was diagnosed by two doctors based on imaging tests and blood tests to exclude other causes. Among 215 patients treated with osimertinib, 28 developed ILD. The median age of patients with ILD was 69.5 years (range, 39.0–80.0). In addition, 29% of patients were men, and 46% had a history of smoking. Eleven patients were re-administered EGFR TKIs, including eight patients treated with osimertinib and three patients treated with alternative EGFR TKIs. Among patients re-challenged with osimertinib, none who previously experienced grade 1 ILD exhibited ILD relapse, even with the same osimertinib dose and without the concurrent administration of systemic steroids. Meanwhile, one of the four patients who previously exhibited grade 2 ILD experienced despite a dose reduction for osimertinib and systemic steroid administration. For patients with EGFR-mutant NSCLC who experience grade 1 ILD during osimertinib therapy, osimertinib re-challenge may be suitable when no other treatments are available. [ABSTRACT FROM AUTHOR]

To observe the platelet lymphocyte ratio (PLR) before treatment and analyze the prognostic factors in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation treated with small molecule tyrosine kinase inhibitor (TKI). Methods Ninety-seven patients with advanced NSCLC who were treated with TKI (Ektorinib or gefitinib) in the observation group, and 90 healthy controls in the control group were included. The peripheral blood of the observation group was collected before TKI treatment and the fasting peripheral blood in the control group was collected to measure PLR. The receiver operating characteristic (ROC) was used to evaluate the diagnostic values of PLR in those patients. The relationship between PLR and clinicopathological features of patients was analyzed. COX proportional hazards regression model was used to analyze the influencing factors of PFS and OS in patients, all patients were followed up, and we recorded the progression-free survival (PFS) and overall survival (OS, and analyzed the risk factors for prognosis. Results The PLR of the observation group and the control group were 196. 6 ± 100. 64 and 117. 8 ± 35. 64, respectively (both P < 0. 05). In the observation group, there were 42 cases of low PLR (PLR ≤ 159) and 55 cases of high PLR (PLR > 159). PLR was associated with distant tumor metastasis in patients with EGFR-mutant advanced NSCLC (X² = 4. 789, P < 0. 05). The PFS of 97 patients ranged from l to 36 months with an average of 9. 4 months and was associated with tumor cell differentiation, distant metastasis, and PLR level (all P < 0. 05); PLR and distant metastasis of tumor were influencing factors of PFS after patients were treated with TKI (95% Cl: l. 100-3. 330, l. 862-6. 979; both P < 0. 05). The OS of 97 patients was 6 to 36 months with an average of 21. l months and was related to distant metastasis, PLR level, and CYFRA21-l (all P < 0. 05); PLR and distant metastasis of tumor were influencing factors of OS after TKI treatment in patients (95 % CI: 1. 127-3. 454, 1. 485 -5. 520; all P < 0. 05). Conclusions PLR is elevated in advanced NSCLC patients with EGFR mutation. PLR is a prognostic factor and can be used as an indicator for evaluating the prognosis of patients with EGFR mutant NSCLC after TKI treatment. [ABSTRACT FROM AUTHOR]