Brain metastases (BM) are common in advanced non-small cell lung cancer (NSCLC), and the prognosis is poor with few therapeutic options. This study evaluated the efficacy of three epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in preventing and treating BM in patients with EGFR mutation-positive advanced NSCLC. Patients with EGFR mutation-positive advanced NSCLC who visited a tertiary referral center from 1 December 2013 to 30 November 2017 were analyzed retrospectively. They received gefitinib, erlotinib, or afatinib until disease progression, death, or intolerable adverse events. The cumulative incidence of subsequent BM of initial non-BM patients, progression-free survival (PFS), and overall survival (OS) of the BM and non-BM patients were estimated and compared using the Kaplan–Meier and log-rank tests. 306 NSCLC patients were enrolled, with 116, 75, and 115 receiving first-line gefitinib, erlotinib, and afatinib, respectively. The afatinib group had a better PFS [12.7 versus 9.8 months; hazard ratio (HR) 0.59, p = 0.001] and OS (39.1 versus 22.0 months; HR 0.64, p = 0.035) than the gefitinib group. Afatinib tended to provide better BM prevention than gefitinib (BM cumulative incidence, HR 0.49; 95% confidence interval 0.34–0.71, p < 0.001) according to a Cox model adjusted for possible confounders. Patients with initial BM had a shorter PFS (p < 0.001) and OS (p = 0.015) than those without initial BM. Among the former, there were no differences in median PFS (p = 0.34) and median OS (p = 0.46) in the three EGFR-TKI groups. Our data suggested that, compared with gefitinib, afatinib provided better benefits significantly in terms of PFS and OS. Both had the same effectiveness in preventing subsequent BM.

Previous studies have demonstrated the association between EGFR mutations and distant metastasis. However, the association for subsequent brain metastasis (BM) in stages I-III non-small cell lung cancer (NSCLC) patients remains inconclusive. We conducted a retrospective analysis to clarify the impact of EGFR mutations on the incidence of BM and associated survival in patients with stage I-III NSCLC. A total of 491 patients screened for EGFR mutations were retrospectively enrolled. Brain MRI or CT was used to detect the BM. Cumulative incidence of subsequent BM and overall survival (OS) after diagnosis of BM were estimated by the Kaplan-Meier method and compared using log-rank test. We performed Cox proportional hazard regression for predictors of subsequent BM and determinants of OS after BM. The cumulative incidence of BM seemed higher in patients harboring EGFR mutations than those without EGFR mutations although it did not reach statistical significance (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 0.73~1.81). After adjusting possible confounders, including age, smoking, stage, and tumor size, EGFR mutation became one of the predictors for subsequent BM (HR = 1.89, 95% CI = 1.12~3.17, p = 0.017). Though there was no statistical difference in survival after BM between patients with EGFR mutations and wild-type EGFR (median survival: 17.8 vs. 12.2 months, HR = 0.79, 95% CI = 0.45–1.40), patients with EGFR 19 deletion (Del) tended to have a longer survival after BM than the non-EGFR 19 Del group (median survival: 29.4 vs. 14.3 months, HR 0.58, 95% CI = 0.32–1.09, p = 0.089). In conclusion, our data suggested EGFR mutation to be one of the predictors for subsequent BM in stage I-III patients. Given the small sample size, more studies are warranted to corroborate our results.

Recent study showed that the combination of erlotinib and bevacizumab had better disease control than erlotinib monotherapy in patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, there is lack of real-world evidence for this therapeutic regimen. We aimed to compare outcomes between patients with EGFR mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) and bevacizumab and those treated with EGFR-TKI alone in a real-world setting. Patients with advanced EGFR-mutant NSCLC who received first-line EGFR-TKI in a tertiary referral center from October 1, 2013 to December 31, 2019 were retrospectively analyzed. We performed 1:2 propensity score-matching: one EGFR-TKI and bevacizumab recipient with two patients who received EGFR-TKI alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The prognostic factors were analyzed using Cox proportional hazards regression analysis. Total 313 patients were enrolled. After propensity score matching, 45 patients who received first-line EGFR-TKI and bevacizumab and 89 patients who received EGFR-TKI alone were analyzed. The combination group showed improved PFS (17.0 vs. 11.0 months; hazard ratio [HR] = 0.48; p = 0.002) compared to the monotherapy group. In subgroup analysis of patients with an L858R mutation, the combination group showed longer PFS (23.1 vs. 10.7 months; HR = 0.40; p = 0.011) and OS (not reached vs. 40.6 months; HR = 0.27; p = 0.040) than the EGFR-TKI monotherapy group. Our data suggest that the combination of EGFR-TKI and bevacizumab could improve PFS in patients with EGFR-mutant NSCLC. In patients harboring L858R mutation, the combination therapy provides better OS than TKI alone.

Background: Researchers have not simultaneously compared the cost‐effectiveness of six immunotherapies with chemotherapy for advanced non‐small cell lung cancer. This study evaluated the cost‐effectiveness across different programmed death‐ligand 1 (PD‐L1) levels.Methods: A Markov model with lifetime horizon was created for seven regimens: pembrolizumab plus chemotherapy (pembro‐chemo), nivolumab plus ipilimumab (nivo‐ipi), nivolumab, ipilimumab plus chemotherapy (nivo‐ipi‐chemo), atezolizumab plus chemotherapy (atezo‐chemo), atezolizumab, bevacizumab plus chemotherapy (atezo‐beva‐chemo), single‐agent pembrolizumab, and chemotherapy alone. Input parameters were derived from trial data, a network meta‐analysis, and other literature. We conducted the analysis from the perspective of US health care sector.Results: For all patients without considering PD‐L1 expression, the incremental cost‐effectiveness ratio (ICER) of pembro‐chemo versus chemotherapy was $183,299 per quality‐adjusted life year (QALY). The preferred regimens based on ICERs differed by PD‐L1 levels. For patients with PD‐L1 ≥50%, pembrolizumab versus chemotherapy and pembro‐chemo versus pembrolizumab resulted in ICERs of $96,189 and $198,913 per QALY, respectively. The other strategies were dominated. For patients with PD‐L1 of 1%–49%, the ICER of pembro‐chemo comparing to chemotherapy was $218,159 per QALY. The other regimens were dominated by pembro‐chemo. For patients with PD‐L1 <1%, nivo‐ipi versus chemotherapy and nivo‐ipi‐chemo versus nivo‐ipi resulted in ICERs of $161,277 and $881,975 per QALY, and the other regimens were dominated strategies. At the willingness‐to‐pay threshold of $150,000 per QALY, pembrolizumab had 87% and pembro‐chemo had 1% probabilities being cost‐effective in patients with PD‐L1 ≥50% and 1%–49%, respectively. Nivo‐ipi had a 34% probability being cost‐effective in patients with PD‐L1 <1%.Conclusions: The PD‐L1 level should be incorporated into treatment decision‐making. Our findings suggest that first‐line pembrolizumab, pembro‐chemo, and nivo‐ipi are the preferred strategies for patients with PD‐L1 ≥50%, 1%–49%, and <1%, respectively.

The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (n = 28) or combination therapy either with chemotherapy or radiotherapy (n = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method and compared using log–rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy.