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Background: Patients with brain oligometastases have better prognosis than those with synchronous extracranial metastases in non‐small cell lung cancer (NSCLC). However, studies focusing on intracranial‐only recurrence after curative surgery remained scarce. This study aimed to explore distinct features of patients with exclusive brain relapse after resection of lung adenocarcinoma. Methods: Records were retrospectively reviewed of 2809 patients who had complete resection and pathologically confirmed stage IB‐IIIA NSCLC in our hospital from October 2012 to September 2019. Patients were enrolled if they were adenocarcinoma and developed intracranial recurrence thereafter. They were divided into two groups depending on whether they had synchronous extracranial metastases. Clinical and pathological features of patients enrolled were collected and compared between groups. Results: Ninety‐seven lung adenocarcinoma patients with intracranial recurrences were enrolled. The median follow‐up time was 40 months. Fifty patients (51.5%) had brain oligometastases and 47 patients had synchronous extracranial metastases (ECM). Multivariate logistic regression suggested EGFR‐sensitive mutation and male sex were positively correlated to brain‐only recurrence (OR = 2.59, 95%CI 1.04–6.84 and OR = 2.58, 95% CI 1.05–6.75), while higher clinical stage was associated with synchronous ECM (stage II (OR = 0.33, 95%CI 0.09–1.14) or stage IIIA (OR = 0.54, 95%CI 0.20–1.38) versus stage I). No other pathological feature (lymphovascular invasion, visceral pleural invasion, low tumor differentiation, etc.) or adjuvant chemotherapy was associated with intracranial‐only relapse after complete resection of primary tumor. Conclusion: Among patients with brain relapse after resection of lung adenocarcinoma, patients with EGFR mutations might have intracranial relapse only without synchronous extracranial metastases. Further prospective studies are warranted to verify this. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0–10 pack-year, OR 0.27, 95%CI: 0.17–0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29–0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged. [ABSTRACT FROM AUTHOR]

Background: In the era of second-generation ALK tyrosine kinase inhibitors (ALK-TKIs), there was a paucity of data regarding the progression patterns, resistant mechanisms, and subsequent therapeutic approaches for ALK-positive (ALK+) non-small cell lung cancer (NSCLC). Methods: Patients with advanced ALK+ NSCLC were retrospectively selected from our center. Cohort 1 consisted of patients who experienced disease progression after receiving first-line alectinib treatment (n = 20), while Cohort 2 included patients who progressed following sequential treatment with crizotinib and second-generation ALK-TKIs (n = 53). Oligo-progression was defined as the occurrence of disease progression in no more than three lesions. Symptomatic progression was determined when patients developed new symptoms or experienced worsening of pre-existing symptoms during radiological progression. Results: The incidence of central nervous system (CNS) progression and symptomatic CNS progression was significantly lower in Cohort 1 compared to patients treated with crizotinib, with rates of 15.0% vs. 56.6% (p = 0.002) and 5.0% vs. 32.1% (p = 0.016), respectively. A total of 60.3% (44/73) patients underwent repeated biopsy and next-generation sequencing subsequent to the second-generation ALK-TKI resistance, with secondary mutation in ALK kinase domain emerging as the predominant mechanism of resistance (56.8%). Local therapy was applied to 50% of oligo-progression cases. Subsequent ALK-TKIs demonstrated significantly prolonged progression-free survival (PFS) (8.6 m vs. 2.7 m, p = 0.021, HR = 0.43, 95%CI: 0.15–0.85) and long-term overall survival (OS) (NA vs. 11.9 m, p = 0.132, HR = 0.50, 95%CI: 0.18–1.25) in patients harboring ALK resistance mutations, compared to those without such mutations. For patients without ALK-resistant mutations following progression on second-generation ALK-TKIs, there was no statistically significant difference in survival outcomes between subsequent chemotherapy or alternative ALK-TKI treatments. Conclusions: First-line alectinib demonstrated superior efficacy in protecting the CNS compared to crizotinib. For patients with ALK-resistant mutations following the resistance to second-generation ALK-TKIs, appropriate sensitive ALK-TKI should be administered; for those without such mutations, the selection of chemotherapy or third-generation ALK-TKI should be based on the patient's overall physical health and personal preferences. [ABSTRACT FROM AUTHOR]

Objectives: Central nervous system (CNS) metastases including brain metastases (BM) and leptomeningeal metastases (LM) are frequent in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), and are correlated with poor outcomes. In this study, we evaluated the efficacy of single-agent furmonertinib 160 mg or combining with anti-angiogenic agent in NSCLC patients who had developed BM/LM progression from previous tyrosine kinase inhibior (TKI) treatment. Methods: EGFR-mutated NSCLC patients who developed BM (the BM cohort) or LM progression (the LM cohort) were included, having received furmonertinib 160 mg daily as second-line or later treatment, with or without anti-angiogenic agents. The intracranial efficacy was evaluated by intracranial progression-free survival (iPFS). Results: Totally 12 patients in the BM cohort and 16 patients in the LM cohort were included. Almost one half of patients in the BM cohort and a majority in the LM cohort had a poor physical status, with a Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. The administration of single-agent furmonertinib or combination treatment achieved a median iPFS of 3.6 months (95%CI 1.435–5.705) in the BM cohort, and 4.3 months (95%CI 2.094–6.486) in the LM cohort. Subgroup and univariate analysis has shown that a good ECOG-PS correlated with a favorable efficacy of furmonertinib in the BM cohort (median iPFS = 2.1 with ECOG-PS ≥ 2 vs. 14.6 months with ECOG-PS < 2, P < 0.05). Overall, any grade of adverse events (AEs) occured in 46.4% of patients (13/28). Among them, 14.3% of patients (4 of 28) had grade 3 or higher AEs, and were all under control, led to no dose reductions or suspension. Conclusion: Single-agent furmonertinib 160 mg or in combination of anti-angiogenic agent is an optional salvage therapy for advanced NSCLC patients who developed BM/LM progression from prior EGFR-TKI treatment, with a promising efficacy and an acceptable safety profile, and is worth of further exploration. [ABSTRACT FROM AUTHOR]

Background: Currently, survival benefit of immunotherapy in advanced non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) is controversial, though it generally indicates poor response and activity. Compared with standard chemotherapy in combination with bevacizumab, first‐line chemotherapy plus immune checkpoint inhibitor (ICI) in advanced NSCLC with EGFR ex20ins remains elusive and lacks real‐world evidence. Patients and Methods: A retrospective real‐world study was conducted to evaluate clinical outcomes of chemotherapy alone (C), chemotherapy plus ICI (C + I), or chemotherapy plus angiogenesis inhibitors (C + A) as first‐line strategies for advanced NSCLC patients with EGFR ex20ins. Investigator‐assessed response and survival outcomes were compared between subgroups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to reveal concomitant alterations and explore the molecular landscape of ex20ins. Results: A total of 164 patients were screened, identifying 35 kinds of ex20ins, and 122 cases treated with C, C + I, and C + A were finally included in the first‐line analysis. C + A achieved much better objective response rate (ORR, 38.1% vs. 18.2%) and significant progression‐free survival (PFS) benefit compared with C (median, 7.73 vs.5.93 months, HR = 0.60, 95% CI: 0.40–0.90, p = 0.014), and it showed similar ORR (38.1% vs. 40.0%), but higher disease control rate (DCR, 96.8% vs. 80.0%) and numerically longer median PFS (7.73 vs. 6.53 months, HR = 0.83, 95% CI: 0.44–1.56, p = 0.30) than C + I. There was no PFS difference between C + I and C, despite of PD‐L1 expression or tumor mutational burden. KEGG analysis revealed concomitant upregulation of PI3K/AKT signaling might mediate intrinsic resistance to ICI in ex20ins. Conclusion: First‐line chemotherapy plus angiogenesis inhibitors might yield more survival benefits than chemotherapy alone for NSCLC with EGFR ex20ins, whereas, it suggests that chemotherapy in combination with ICI might not obtain a better survival benefit for this subset of patients. Activation of PI3K/AKT signaling might mediate intrinsic immunosuppression in NSCLC with EGFR ex20ins. [ABSTRACT FROM AUTHOR]

Purpose: After progression to immunotherapy, the standard of care for non-small cell lung cancer (NSCLC) was limited. Administration of the same or different immune checkpoint inhibitors (i.e., ICI rechallenge) may serve as a novel option. The present study aimed to evaluate the efficacy of ICI rechallenge for NSCLC and explore prognostic factors. Methods: In this retrospective cohort study, data of advanced or metastatic NSCLC patients rechallenged with ICI at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College between December 2018 and June 2021 were retrieved. Progression-free, overall survivals (PFS; OS), etc. were calculated. Subgroup analyses were conducted according to baseline characteristics, prior treatment results, etc. for prognostic factor exploration using the Cox model. Results: Forty patients were included. Median age was 59 years. Thirty-one (78%) were male. Twenty-seven (68%) were smokers. Adenocarcinoma (28 [70%]) was the major histological subtype. Median PFS of patients receiving initial ICI was 5.7 months. The most common rechallenge regimens were ICI plus chemotherapy and/or angiogenesis inhibitor (93%). Seventeen (43%) were rechallenged with another ICI. Median PFS for ICI rechallenge was 6.8 months (95% CI 5.8–7.8). OS was immature. Tendencies for longer PFS were observed in nonsmoker or patients with adenocarcinoma, response of stable/progressive disease in initial immunotherapy, or whose treatment lines prior to ICI rechallenge were one/two. However, all results of prognostic factors were nonsignificant. Conclusion: ICI rechallenge may be an option for NSCLC after progress to immunotherapy. Further studies to confirm the efficacy and investigate prognostic factors are warranted. [ABSTRACT FROM AUTHOR]

Introduction: EGFR mutations in non-small cell lung cancer (NSCLC) are associated with a poor response to immune checkpoint inhibitors (ICIs), and only 20% of NSCLC patients harboring EGFR mutations benefit from immunotherapy. Novel biomarkers or therapeutics are needed to predict NSCLC prognosis and enhance the efficacy of ICIs in NSCLC patients harboring EGFR mutations, especially lung adenocarcinoma (LUAD) patients, who account for approximately 40–50% of all NSCLC cases. Methods: An ARID1A-knockdown (ARID1A-KD) EGFR-mutant LUAD cell line was constructed using lentivirus. RNA-seq and mass spectrometry were performed. Western blotting and IHC were used for protein expression evaluation. Effects of 3-MA and rapamycin on cells were explored. Immunofluorescence assays were used for immune cell infiltration examination. Results: ARID1A expression was negatively associated with immune cell infiltration and immune scores for ICIs in LUAD with EGFR mutations. In vitro experiments suggested that ARID1A-KD activates the EGFR/PI3K/Akt/mTOR pathway and inhibits autophagy, which attenuates the inhibition of Rig-I-like receptor pathway activity and type I interferon production in EGFR-mutant LUAD cells. In addition, 3-MA upregulated production of type I interferon in EGFR-mutant LUAD cells, with an similar effect to ARID1A-KD. On the other hand, rapamycin attenuated the enhanced production of type I interferon in ARID1A-KD EGFR-mutant LUAD cells. ARID1A function appears to influence the tumor immune microenvironment and response to ICIs. Conclusion: ARID1A deficiency reverses response to ICIs in EGFR-mutant LUAD by enhancing autophagy-inhibited type I interferon production. 4p38v18Tik7_Gskdth_Seh Video Abstract [ABSTRACT FROM AUTHOR]

Objectives: To analyze the clinical relevance of heterogeneous phenotypes of peripheral circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC). Materials and Methods: CTCs in 5 mL venous blood were enriched using the Canpatrol™ CTC technique in 82 NSCLC patients. And then, CTCs were subjected to RNA in situ hybridization with a combination of epithelial (EpCAM and CK8/18/19) and mesenchymal (vimentin and TWIST1) markers. Results: According to the fluorescent dots, CTCs were classified into three groups, including epithelial CTCs (E-CTC), hybrid epithelial/mesenchymal phenotypes (E/M-CTCs) and mesenchymal CTCs (M-CTCs). In 82 NSCLC cohort, only 2 patients didn't detect CTCs, the overall CTCs detection rate was 97.5% (80/82). For 60 treatment naïve NSCLC, only one patient didn't detect CTCs. The median number of total CTCs, hybrid E/M phenotype CTCs, E-CTCs and M-CTCs per 5 mL blood was 22 (range 1–90), 13 (range 0–83), 1 (range 0–17 and 0–47), respectively. Hybrid E/M CTCs, especially the e = m-CTCs, significantly differed between patients with and without distant metastasis. M-CTCs in advanced NSCLC patients were significantly more than the numbers observed in early stage patients. Patients with pure hybrid E/M-CTCs showed a lower proportion in distant metastasis positive cohort compared to negative ones (7% vs 22%), while patients with E + E/M CTCs (20% vs 9%) and E/M + M CTCs (33% vs 20%) showed a higher proportion. CTCs dynamic changes after treatment in 12 advanced NSCLC patients suggested that hybrid E/M-CTCs were related to the primary tumor size at baseline, while M-CTCs may suggest the progression of NSCLC. Conclusion: We concluded that E-CTCs with a hybrid E/M phenotype are associated to metastasis in therapy-naïve NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) metastases in patients with ALK-positive non-small cell lung cancer (NSCLC) are a cause of substantial morbidity and mortality. Although alectinib had demonstrated promising intracranial efficacy in several clinical trials, data were limited on its CNS activity in real-world settings.Methods: In this retrospective study, ALK-positive NSCLC patients with brain metastases (BM) or leptomeningeal metastases (LM) from six hospitals in China were divided into three cohorts based on the treatment history before the administration of alectinib. ALK-TKI-naive patients were enrolled in cohort 1, cohort 2 included patients who experienced intracranial progression with or without extracranial progression after treatment with crizotinib, and cohort 3 included patients who developed progression only in CNS following treatment with other second-generation ALK-TKIs. The definition and evaluation of intracranial and extracranial lesions were based on Response Evaluation Criteria in Solid Tumors version 1.1.Results: Sixty-five patients were eligible and included in our study (cohort 1: 20, cohort 2: 32, cohort 3: 13). For the overall population and patients with uncontrolled CNS metastases, similar intracranial response in CNS target lesions was observed: cohort 1: 81.8% and 80%; cohort 2: 76.5% and 86.7%; cohort 3: 42.8% and 33.3%. For patients in these three cohorts, 75% (6/8), 78.6% (11/14), and 83.3% (5/6) were reported to have significant improvement in CNS-related symptoms respectively. The number of patients who were in need of mannitol or corticosteroids decreased remarkably after the treatment of alectinib (p < 0.001), and there was also a steep fall-over in the number of patients with ECOG ≥2 points before and after the administration of alectinib (p = 0.003). All patients (8/8) diagnosed with LM ± BM experienced substantial alleviation in CNS-related symptoms. In cohort 1 and cohort 2, no significant difference in CNS-time to progression was found between patients with symptomatic or asymptomatic BM when treated with alectinib alone.Conclusions: Our study substantiated the potent CNS activity of alectinib in real-world settings. Patients with symptomatic and asymptomatic BM could benefit from alectinib comparatively, which indicated that alectinib alone might defer the timing of local treatment. However, our results should be treated cautiously owing to limited sample size. [ABSTRACT FROM AUTHOR]

ARID1A is a key component of the SWI/SNF chromatin remodeling complexes which is important for the maintaining of biological processes of cells. Recent studies had uncovered the potential role of ARID1A alterations or expression loss in the therapeutic sensitivity of cancers, but the studies in this field requires to be further summarized and discussed. Therefore, we proposed a series of mechanisms related to the resistance to EGFR-TKIs induced by ARID1A alterations or expression loss and the potential therapeutic strategies to overcome the resistance based on published studies. It suggested that ARID1A alterations or expression loss might be the regulators in PI3K/Akt, JAK/STAT and NF-κB signaling pathways which are strongly associated with the resistance to EGFR-TKIs in NSCLC patients harboring sensitive EGFR mutations. Besides, ARID1A alterations or expression loss could lead to the resistance to EGFR-TKIs via a variety of processes during the tumorigenesis and development of cancers, including epithelial to mesenchymal transition, angiogenesis and the inhibition of apoptosis. Based on the potential mechanisms related to ARID1A, we summarized that the small molecular inhibitors targeting ARID1A or PI3K/Akt pathway, the anti-angiogenic therapy and immune checkpoint inhibitors could be used for the supplementary treatment for EGFR-TKIs among NSCLC patients harboring the concomitant alterations of sensitive EGFR mutations and ARID1A. [ABSTRACT FROM AUTHOR]

Purpose: Osimertinib, a third-generation epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), has demonstrated substantial clinical benefit in patients with non-small-cell lung cancer (NSCLC) who were resistant to early-generation EGFR-TKIs and had acquired a T790M mutation. The aim of our study was to identify the mechanisms underlying resistance to osimertinib and to correlate them with clinical outcomes. Methods: We retrospectively analyzed patients with advanced NSCLC who received osimertinib for T790M-mutated acquired resistance to prior EGFR-TKIs between March 1, 2017 and December 31, 2018. Patients with paired molecular data of pre-osimertinib and after resistance development, which were not confirmed with small-cell lung cancer (SCLC) transformation, were included in the molecular analysis set. Results: Of 49 patients evaluated in the molecular analysis set, 24 patients maintained T790M mutation, while 25 patients exhibited T790M-loss. Molecular modifications were identified in 27 of 49 patients including EGFR acquired mutations (C797S, C796S, G796S, V802I, V834L, E758D and G724S), non-EGFR-dependent mutations (PIK3CA, ALK, BRAF, KRAS and TP53), EGFR amplification and MET amplification. At data cutoff, median progression-free survival (PFS) was 9.3 months in the T790M-retain group compared with 7.8 months in T790M-loss patients (P = 0.053). Median PFS was significantly longer in patients with EGFR-dependent resistance mechanism (13.5 months) than in those with alternative pathway activation (8.2 months; P = 0.012). Conclusions: The study revealed heterogeneous mechanisms of resistance to osimertinib in advanced NSCLC patients and their association with clinical outcomes. Patients who maintained T790M mutation or with EGFR-dependent resistance mechanism had longer clinical outcome benefits. [ABSTRACT FROM AUTHOR]

Background: ROS1 gene fusion represents a specific subtype of non‐small cell lung cancer (NSCLC). Crizotinib is recommended for ROS1‐positive NSCLC due to its favorable outcome in published clinical trials. However, due to the low incidence of ROS1‐positive NSCLC, there is limited information on real‐world clinical outcomes in patients treated with either crizotinib or platinum‐based doublet chemotherapy. Methods: Outcomes were recorded in 102 patients with stage Ⅲb or Ⅳ NSCLC who were treated at four Chinese hospitals between April, 2010 and June, 2019. Results: Of the 102 patients followed, 71.6% were females, 81.4% were non‐smokers, and 98.0% had adenocarcinoma. First‐line treatment with crizotinib achieved a significantly longer median progression‐free survival (PFS) compared with platinum‐based chemotherapy (14.9 months vs 8.5 months, respectively; P <.001). Next‐generation sequencing (NGS) identified 61 patients who had ROS1 fusion variants, including CD74 (n = 33) and non‐CD74 (n = 28) variants. In patients harboring CD74 fusion variants, the median PFS with first‐line crizotinib treatment was significantly longer than in those harboring non‐CD74 fusion variants (20.1 months vs 12.0 months, respectively; P =.046). However, in patients treated with platinum‐based chemotherapy, there was no significant difference in PFS between the CD74 and non‐CD74 variant groups (8.6 months vs 4.3 months, respectively; P =.115). Overall survival (OS) was not reached. Conclusions: First‐line therapy with crizotinib is more beneficial than platinum‐based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants. Patients harboring CD74 fusion variants appear to respond better to crizotinib. [ABSTRACT FROM AUTHOR]

Aim: Valuable and convenient prognostic predictors are essential for targeted therapy of non–small cell lung cancer (NSCLC). Patients with early‐stage cancer and EGFR mutations who's neutrophils‐to‐lymphocytes rate (NLR) could be prognostic factor to evaluate efficacy. However, the prognostic role of NLR in patients receiving ALK inhibitors has not been established. Additionally, the relation between the efficacy of ALK inhibitors and derived NLR (dNLR), platelets‐to‐lymphocytes rate (PLR), white blood cells (WBC) and hemoglobin (HGB) are still unknown. Methods: This is a retrospective single‐center study and enrolled 113 staged IIIB–IV ALK‐positive NSCLC patients who had received crizotinib treatment. Pretreatment NLR, dNLR, PLR, WBC, HGB were collected and calculated. Cox regression analysis were conducted to study the prognostic roles of NLR, dNLR, PLR, WBC, and HGB on progression‐free survival (PFS) and overall survival (OS). Z‐test was utilized to identify the difference among all predictive factors' receiver‐operating characteristics (ROC) curves. Results: The median PFS and OS were 10.1 and 23.4 months. Elevated NLR, dNLR, PLR and decreased HGB were associated with worse PFS (95% confidence interval [CI], 1.078–2.304, P = 0.018; 95% CI, 1.043–2.222, P = 0.028; 95% CI, 1.257–2.757, P = 0.002; 95% CI, 0.368–0.843, P = 0.005, respectively) and OS (95% CI, 1.698–5.721, P < 0.001; 95% CI, 1.273–3.984, P = 0.005; 95% CI, 2.174–6.347, P < 0.001; 95% CI, 0.246–0.710, P = 0.001, respectively). Z‐test revealed there were no significant differences between single factors or combination of them to predict the efficacy. Conclusions: Trend of NLR, dNLR, PLR and WBC could be used to identify patients progress status in ALK‐positive NSCLC patients receiving crizotinib. Combination of all biomarkers is no superior to single biomarker. [ABSTRACT FROM AUTHOR]

aims to quantify patients' risk-benefit preferences for chemotherapy in the treatment of non-small cell lung cancer (NSCLC), and to elicit their willingness to pay (WTP) for treatment outcomes. Methods: A face-to-face discrete choice experiment (DCE) was conducted on NSCLC patients in four tertiary hospitals each from Beijing, Shanghai, Guangzhou and Chengdu in China. Patients were invited to complete choice questions that constructed by seven attributes: progression-free survival (PFS), disease control rate (DCR), rash, nausea and vomiting, tiredness, mode of administration and out-of-pocket costs. A mixed logit model was used to evaluate the choice model. Estimates of relative preferences and marginal willingness to pay for each attribute were then explored. Results: A total of 361 patients completed the survey. Improvements in PFS (10, 95% CI: 8.4–11.6) were the most important attribute for patients, followed by increase in DCR (4.6, 95% CI: 3.4–5.8). Tiredness (3.9, 95% CI: 2.9–5.1) was judged to be the most important risk. While remaining attributes were ranked in decreasing order of importance: nausea and vomiting (1.9, 95% CI: 0.9–3.0), mode of administration (0.8, 95% CI: 0.2–1.4) and rash (0.5, 95% CI: −0.6–1.5). There was little variation in preferences among patients with different sociodemographic characteristics. Patients were monthly willing to pay $2304 (95% CI, $1916–$2754) that guaranteed 11 months of PFS, followed by $1465 (95% CI, $1163-$1767) per month to improve their disease control rate by 90%. Conclusion: The results suggested that efficacy was the most important attribute for patients. Side effects, mode of administration and treatment cost significantly influenced patient preferences. Patient engagement in prioritizing their treatment preferences should be emphasized during the clinical decision-making process and regimen implementation. [ABSTRACT FROM AUTHOR]

Objectives: Crizotinib has demonstrated good efficacy in patients with anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Continuing crizotinib therapy beyond progressive disease (CBPD) can achieve ongoing survival benefit in real‐world clinical practice. In terms of survival, progression‐free survival (PFS), the most commonly used endpoint in efficacy evaluations, may not provide accurate information on the impact of this intervention when crizotinib is administered in sequential therapy. Materials and Methods: A single‐center, retrospective study of 201 ALK‐positive advanced NSCLC patients was conducted to analyze the PFS, overall survival (OS), and treatment duration (TD) of crizotinib. The correlations between the TD of crizotinib and OS in CBPD and non‐CBPD groups of patients were compared. Results: All patients were treated with crizotinib, 150 of whom eventually developed progressive disease (PD). The median PFS1 and PFS2 were 13.2 months and 10.5 months, respectively. The OS of the whole population was 50.5 months. The median TD was 20.7 months, which is shorter than direct PFS1 + PFS2. The TD of crizotinib in CBPD group was significantly longer than that in non‐CBPD group (median 39.7 vs 15.0 months, P < .001). TD correlated better with OS (R = .79) than PFS (R = .64) in the CBPD group. Conclusions: Crizotinib showed good efficacy in patients with ALK‐positive advanced NSCLC. Instead of PFS, treatment duration might be a more reasonable surrogate clinical endpoint in patients who received crizotinib in sequential therapy. [ABSTRACT FROM AUTHOR]

Aim: Most epidermal growth factor receptor (EGFR) gene mutations affecting exon 19 (inframe deletions; 19 Del) and 21 (L858R), while the rest (referred as uncommon EGFR mutation) have not been fully described due to their rarity. Here we present a retrospective study that investigated clinical characteristics and outcome of patients with different EGFR mutations. Methods: We retrospectively analyzed the EGFR mutation pattern and its association with clinical‐pathological characteristics from 100 cases of nonsmall‐cell lung cancer (NSCLC) harboring EGFR mutations, and compiled the genotype response data for NSCLC patients with common and uncommon EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs). Patients with advanced EGFR‐mutated NSCLC were enrolled and treated with icotinib (oral administration, 125 mg, thrice per day). Results: Among 100 patients, 85 and 15 had common and uncommon mutations, respectively. Four patients had a single mutation in 18 or 20 exon, and 11 had a complex mutation with del‐19 or L858R. There was no significant association between the presence of different mutation type and the type of any clinical and pathological characteristics. Prolonged but not significant progression‐free survival (PFS) was noted in patients with common EGFR mutations (18.07 [14.00–26.23] vs 12.9 [8.43–23.27], P = 0.056). Patients without brain metastases had increased PFS to icotinib than those with brain metastases (18.07 [95% confidence interval, CI 14.77–27.03] vs 13.17 [95% CI 8.63–22.63], P = 0.038). Conclusion: Uncommon EGFR mutations comprised 15% of all mutated patients, in which most were complex mutations. Compared with common EGFR mutation, uncommon EGFR mutations were associated with a modest sensitivity to EGFR TKIs. Our findings will be helpful to make clinical decision and select the appropriate therapy for EGFR‐mutated NSCLC patients. [ABSTRACT FROM AUTHOR]

Introduction Anaplastic lymphoma kinase ( ALK ) rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK -rearrangement can be effectively treated with crizotinib. However, magnitude and duration of responses are found to be heterogeneous. This study explored the clinical efficacy of crizotinib in different ALK variants. Methods Among 96 ALK -rearrangement patients treated with crizotinib, 60 patients were identified with tumor specimens that could be evaluated by next-generation sequencing (NGS). We retrospectively evaluated the efficacy of crizotinib in different ALK variants. Results The median Progression-free survival (PFS) of the 96 ALK -rearrangement patients was 14.17 months. Among the 60 patients with NGS results, the most frequent variants were variant 3a/b (33.33%), variant 1 (23.33%) and variant 2 (15.00%). The percentage of rare EML4 - ALK variants and non EML4 - ALK variants were 10.00% and 18.33%. Survival analysis showed that patients with variant 2 appeared to have longer PFS than others (P = .021); also, patients with TP53 mutation seemed to have an unfavorable PFS than those with TP53 wild-type with a borderline p value (P = .068). After adjusting for other baseline characteristics, EML4 - ALK variant 2 was identified as an important factor for a better PFS of crizotinib. We also found that patients with variant 3a/b had shorter duration of response to crizotinib; however, no significant difference of PFS was observed between the PFS of variant3a/b and non-v3 EML4 - ALK variants. Conclusions Our results indicate prolonged PFS in patients with EML4 - ALK variant 2. [ABSTRACT FROM AUTHOR]

Poor prognosis of advanced non-small-cell lung cancer ( NSCLC) patients and the promising therapeutic effect of platinum urge the oncologists to evaluate the role of platinum doublet as second-line chemotherapy and establish the definition of platinum sensitivity in NSCLC. We retrospectively analyzed 364 advanced NSCLC patients who received platinum-doublet regimens as second-line chemotherapy after platinum-based first-line treatment. Patients were divided into four groups by their time-to-progression ( TTP) after first-line chemotherapy: 0-3, 4-6, 7-12, and >12-month group, respectively. Treatment efficacy of patients' overall survival ( OS), progression-free survival ( PFS), and response rate ( RR), as well as treatment-related toxicity, were compared among the four groups. A prognosis score system and a nomogram were established by Cox proportional hazard model, and validated by concordance index (c-index). Median OS was 14.0, 16.0, 20.0, 25.0 months for patients in the 0-3, 4-6, 7-12, >12-month group, respectively. Age ≤60 years ( P = 0.002), female ( P = 0.019), and TTP>12 months ( P = 0.003) were independent prognostic factors. Prognostic score was calculated by adding 1 point each for any of the above three indicators, with a c-index of 0.590 (95% confidential interval [ CI], 0.552-0.627). Median OS were equal to 25.0, 16.0, and 11.0 months for best (2-3 points), intermediate (1 point) and worst (0 point) category, respectively ( P < 0.0001). A nomogram that integrated patient's age, gender, and TTP for OS has a c-index of 0.623 (95% CI, 0.603-0.643). Female, younger than 60 years, and TTP greater than 12 months may indicate prolonged survival after platinum-doublet second-line chemotherapy in advanced NSCLCpatients. [ABSTRACT FROM AUTHOR]