Search

Background Epidermal growth factor-tyrosine kinase inhibitors ( EGFR- TKIs) are one of the effective medicines in advanced lung adenocarcinoma leptomeningeal metastasis ( LM) treatment in recent years. Methods This paper reports two cases of advanced lung adenocarcinoma with exon-EGFR19 mutation. LM occurred during gefitinib treatment with an extracranial condition under control. Later, erlotinib was adopted with a recurrent response. Results The progression free survival of both patients was over six months and their LM was under control for six and a half and nine months, respectively. LM may be sensitive on different levels to different EGFR- TKIs. Conclusion Erlotinib can be used to replace gefitinib if intracranial tumor progress occurs during gefitinib treatment. However, our conclusion still needs to be proven by further clinical research. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy (ACT) is considered for high‐risk patients in stage IB lung adenocarcinoma (LUAD). However, these risk factors are recognized as negative prognostic factors, not as predictors of ACT efficacy. This study aimed to analyze the efficacy of ACT in stage IB patients by retrospectively examining patients who had recurrence. Methods: We reviewed 1399 patients with stage IB (American Joint Committee on Cancer 7th edition) LUAD from 2012 to 2017 in our institution and found 147 patients with recurrence. The last follow‐up date was December 30, 2021. One‐to‐one propensity‐score matching (PSM) was used to reduce the potential selection bias. Results: Fifty‐five (37.4%) patients had received ACT and 92 (62.6%) had not (non‐ACT). Patients with ACT were younger (p < 0.001), had larger tumors (p < 0.001) and more lymphovascular invasion (p = 0.02), and seemed to have less distant recurrence (p = 0.001). After PSM, 110 patients were matched and baseline characteristics were balanced. ACT was not associated with improved disease‐free survival (DFS) after matching (mDFS = 23.5 m for ACT vs. 29.5 m for non‐ACT, p = 0.13). ACT failed to prolong DFS of patients in the extracranial recurrence subgroup and EGFR mutation subgroups, and was even associated with shorter DFS in intracranial relapsed patients (mDFS = 30.3 m vs. 33.5 m, p = 0.083) and patients with tumor ≤30 mm (mDFS = 21.9 m vs. 30.8 m, p = 0.076). Conclusion: In patients who were destined to develop recurrence after completely resected stage IB LUAD, ACT might not be associated with improved DFS. Further large multicenter studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: Circulating tumor DNA (ctDNA) monitoring proves to be a promising approach to assess response and predict survival in epidermal growth factor receptor (EGFR)‐mutated non‐small‐cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs). However, whether the dynamic changes in ctDNA EGFR mutation status have the same predictive value as ctDNA remains unknown. This study aims to explore the predictive value of dynamic changes in both ctDNA and ctDNA EGFR status. Methods: A retrospective analysis was performed using 91 ctDNA samples from a cohort of 28 patients who were diagnosed with EGFR‐mutated NSCLC and treated with EGFR‐TKIs, including 14 patients treated with first‐/second‐generation TKIs and 14 treated with osimertinib. Blood samples at baseline (BL), within 4 weeks after TKI initiation (Week4), within 12 weeks before progression (pre‐PD), and at progression were collected. The relationship alternatives in ctDNA status, ctDNA EGFR status and response to EGFR‐TKIs as well as progression‐free survival (PFS) were analyzed. Results: We categorized 20 BL‐ctDNA positive patients with available Week4‐ctDNA into two groups: ctDNA‐clearance (N = 7, 35%) and ctDNA‐non‐clearance (N = 13, 65%). The ctDNA‐clearance group had better PFS than the ctDNA‐non‐clearance group (ctDNA‐clearance vs. ctDNA‐non‐clearance, p = 0.091, hazard ratio [HR] = 0.42, 95% confidence interval [CI] = 0.15–1.19). According to Week4‐EGFR status, we observed that PFS was significantly longer in EGFR‐clearance patients than EGFR‐non‐clearance groups, (p = 0.011, HR = 0.23, 95% CI = 0.08–0.72). We then categorized patients into three subgroups according to Week4‐ctDNA and Week4‐EGFR status: non‐clearance (N = 9), only‐EGFR‐clearance (concomitant alterations non‐clearance) (N = 4), and all‐clearance (N = 7). The nonclearance group had a significantly worse PFS than the all‐clearance group (median PFS = 5.07 vs. 11.40 months, p = 0.029, HR = 3.45, 95% CI = 1.05–11.49). The only‐EGFR‐clearance group had a similar PFS to the all‐clearance group (p = 0.607), which was longer than that of the non‐clearance group (median PFS = 9.20 vs. 5.07 months, p = 0.060, HR = 0.25, 95% CI = 0.05–1.18). We found that the all‐clearance group had a similar objective response rate (ORR) to the only‐EGFR‐clearance group (p = 1.000) and a higher ORR than the non‐clearance group (p = 0.012). Conclusion: Monitoring of EGFR clearance in ctDNA is promising and cost‐effective in assessing response and predicting survival in EGFR‐mutated NSCLC patients treated with EGFR‐TKIs, with similar predictive value to ctDNA surveillance. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune‐related adverse events (irAEs) remain poorly understood, especially in a real‐world setting. Methods: A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD‐L1) monotherapy, anticytotoxic T‐lymphocyte antigen‐4 monotherapy, or combination therapy. Results: In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28–87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3–5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0–1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD‐L1 expression (≥1%) and who received first‐line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p < 0.001). Conclusions: The incidence rate of irAEs was 26.9% in a real‐world setting. IrAEs might be related to a better DCR, but clinicians should be more aware of irAE recognition and management in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Small cell lung cancer (SCLC) is one of the most aggressive malignancies characterized by neuroendocrine (NE) differentiation. The Delta‐like protein 3 (DLL3), as a direct downstream target of ASCL1, is involved in NE differentiation and carcinogenesis of SCLC. This study aims to investigate the relationship between ASCL1 and DLL3 expressions and their clinicopathological implications in SCLC. Methods: A total of 247 surgically resected pure SCLC samples with limited clinical stage and follow‐up data were retrieved in this retrospective study. ASCL1 and DLL3 protein expression was detected by immunohistochemistry staining. The correlations between ASCL1 and DLL3 expressions, as well as their clinicopathological features, were analyzed by χ2 tests. Disease‐free survival (DFS) and overall survival (OS) in SCLC patients with ASCL1/DLL3 low and high expressions were compared by the Kaplan‐Meier method and log‐rank tests. Results: ASCL1 high expression was detected in 105 (42.5%) patients. Its expression was positively correlated with the clinical stage (p = 0.02) and nerve invasion (p = 0.03). DLL3 high expression was observed in 188 (72.8%) patients and was correlated with vascular invasion (p = 0.04). ASCL1 expression was positively associated with DLL3 expression (p = 0.03). In addition, DLL3 expression has a strong correlation with the expression of thyroid transcription factor‐1 (TTF1) and conventional NE markers. Conclusion: ASCL1 and DLL3 were highly expressed in SCLC tumor samples, and a positive correlation between these two markers was observed. Co‐analysis of ASCL1 and DLL3 may identify a distinct SCLC subgroup benefit from targeted therapy. Therefore, ASCL1 and DLL3 could be potential biomarkers served for the selection of related patients. [ABSTRACT FROM AUTHOR]

Background: There is limited data on the clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in a real‐world setting for Chinese patients with advanced ALK+ NSCLC. Methods: The medical records of patients who received sequential therapy with first‐line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK‐TKIs) were collected from six centers in China. Combined time treatment to failure (C‐TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause. Results: A total of 61 patients were included in our study. Fifty‐two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK‐TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow‐up of 34.3 months, C‐TTF was 39.2 months and estimated 5‐year OS was 68.6% in the overall population. Conclusion: Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely. [ABSTRACT FROM AUTHOR]

Background Patients and Methods Results Conclusion Dacomitinib is a second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which is superior to first‐generation EGFR TKI in ARCHER 1050. However, the activity of dacomitinib in the central nervous system (CNS) is not known as ARCHER 1050 did not include patients with baseline brain metastases. This study aimed to describe dacomitinib's activity in the CNS in a real‐world setting.Thirty‐two patients who were receiving dacomitinib for advanced non‐small‐cell lung cancer (NSCLC) with EGFR mutations and brain metastasis were included in this study. Patients who received prior EGFR TKIs were excluded from this trial. Case report forms were collected to determine treatment outcomes.Among 32 patients with EGFR‐mutated NSCLC and brain disease, eight were included in the CNS evaluable for response group. The intracranial objective response rate (iORR) was 87.5% (95% confidence interval [CI] 47.3–99.7%) and the intracranial disease control rate (iDCR) was 100% (95% CI 63.1–100%). In 30 evaluable patients with measurable or nonmeasurable brain lesions, the iORR was 66.7% (95% CI 47.2–82.7%) and the iDCR was 100% (95% CI 88.4–100%). Median intracranial duration of response (iDoR) and intracranial progression‐free survival (iPFS) were not reached, with a one‐year iDoR rate of 72.2% (95% CI 48.7–95.7%) and a 1‐year iPFS rate of 71.2% (95% CI 51.0–91.4%), respectively. The majority of patients experienced low‐grade (G1/2) toxicities, which are reversible.This study suggests that dacomitinib demonstrated CNS efficacy in patients with EGFR TKI‐naïve EGFR‐mutated NSCLC in the real‐world setting. The safety profile was tolerable and manageable. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved the prognosis of mutant lung cancer; however, the clinical application value of TKIs for nonclassical EGFR mutation is unclear, especially for patients with rare uncommon mutations. Methods: A retrospective study based on electronic medical records was conducted to collect data on the effectiveness of afatinib in patients with stage IIIB/IV lung adenocarcinoma (LUAD) bearing uncommon mutations between January 2017 and January 2021. Results: Forty‐two patients with uncommon mutations treated with afatinib were enrolled. The objective response rate (ORR) was 50.0% (10 of 20 patients). The median time to treatment failure (TTF) was 11.7 months (95% confidence interval = 8.5–18.3 months). Of the 42 patients, the median TTF was 15.0, 11.7, and 16.6 months in patients with Gly719Xaa (G719X), Ser768Ile (S768I), and Leu861Gln (L861Q) mutations, respectively. In patients with the rare uncommon mutation, the median TTF was 10.0 months, and the ORR was 50.0%. Afatinib demonstrated clinical activity across a set type of specific rare uncommon mutations, including EGFR L747P, A767_V769dup, and L833V/H835L, with a case having a TTF of more than 1 year. Molecular profiling reports of 16 afatinib‐resistant biopsy samples were available, and the secondary T790M mutation was detected in one patient with L833V/H835L mutation and one harboring S768I/L858R mutation. Conclusions: Our findings suggested that afatinib is effective in patients with uncommon mutations. Mechanisms of afatinib resistance vary and need further investigation. [ABSTRACT FROM AUTHOR]

Background: The optimal strategy was not established for patients who initially responded to gefitinib although re-administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been proven to be an option. Gefitinib and erlotinib were compared as salvage treatment after gefitinib failure. Methods: Thirty-eight lung adenocarcinoma patients were analyzed retrospectively as they received the second EGFR-TKIs treatment with either gefitinib or erlotinib. All of them had obtained disease control from initial gefitinib. Sixteen patients received gefitinib (G-G group) and 22 patients received erlotinib (G-E group). Results: Of all patients, progress free survival (PFS) and overall survival (OS) were three and 12 months, respectively, and the disease controlled rate (DCR) of the second EGFR-TKIs treatment was 52.6%. One patient (6.3%) had partial remission (PR) and 10 (62.5%) had stable disease (SD), in the G-G group, whereas, three (13.6%) had PR and six (27.2%) had SD, in the G-E group. There was no statistical significance observed, although the DCR in the G-G group was higher than that in G-E group (68.8% vs. 40.8%, P= 0.09). Adverse events of both gefitinib and erlotinib were mild and administered. The median PFS and OS in G-G and G-E groups were similar (PFS four vs. three months; OS 22 vs. 12 months). In multivariate analysis, patients with SD in initial gefitinib treatment had significantly longer OS ( P= 0.04). Conclusions: Gefitinib as well as erlotinib could be an option for patients who benefited from prior gefitinib treatment. Patients with SD in initial gefitinib obtained a significantly longer OS than those with PR. [ABSTRACT FROM AUTHOR]

Background: For advanced nonsquamous non‐small cell lung cancer (NSCLC), the mechanisms of resistance to first‐line immunotherapy are not clear. Immune checkpoint inhibitors (ICIs) in combination with agents targeting other pathways may serve as second‐line therapy options. Apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) could increase the efficacy of camrelizumab (an ICI agent). The efficacy and safety of this combination regimen as a second‐line therapy for NSCLC patients after failure on first‐line immunotherapy has not previously been evaluated. Methods: In this single‐arm, multicenter, phase II trial, metastatic nonsquamous NSCLC patients previously treated with single‐agent ICI or ICI plus chemotherapy will be enrolled. Participants will receive intravenous camrelizumab 200 mg D1 and oral apatinib 250 mg D1‐21 for a 21‐day cycle. The study treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is progression‐free survival by investigator. Secondary endpoints are overall survival, objective response rate, disease control rate, duration of response by investigator, quality of life, safety, and toxicity. Conclusions: This trial will provide evidence of the benefit of treatment with camrelizumab combined with apatinib in advanced nonsquamous NSCLC patients who were previously treated with first‐line immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Transformation to small cell lung cancer (SCLC) is a resistance mechanism of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) patients treated with EGFR tyrosine kinase inhibitors (TKIs). Here, we describe the clinical characteristics and prognosis of these patients and explore the treatment modes after transformation. Methods: EGFR‐mutant LADC patients with SCLC transformation were retrospectively included in the study. Demographic and clinical data were collected. Survival outcomes and corresponding influential factors were analyzed. Results: Twenty‐nine patients were included in the study. The median progression‐free survival (PFS) of patients who received first‐line EGFR‐TKIs was 13.1 months. The median time to SCLC transformation was 27.5 months. After transformation, the objective response rates of patients who received first‐line chemotherapy with or without EGFR‐TKIs were 43.8% and 37.5%, respectively. The median PFS of patients reveiving chemotherapy with EGFR‐TKIs was significantly longer than that of patients receiving chemotherapy without EGFR‐TKIs (5.2 vs. 3.0 months; HR, 0.19; 95% CI: 0.05–0.72; p = 0.014). However, there was no significant difference in median overall survival (OS) between patients who received chemotherapy with or without EGFR‐TKIs (14.8 vs. 13.0 months; p = 0.474). In the multivariate Cox proportional hazards regression analysis, both anti‐angiogenic treatment (HR, 0.04; 95% CI: 0.01–0.29; p = 0.001) and local radiotherapy (HR, 0.28; 95% CI: 0.08–0.97; p = 0.044) were significantly associated with better patient OS after transformation. Conclusions: Compared with chemotherapy alone, the combination of chemotherapy and EGFR‐TKIs as first‐line treatment after SCLC transformation can benefit patients in PFS but not in OS. However, anti‐angiogenic therapies and local radiotherapy can significantly prolong OS after transformation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that PD‐1 inhibitors are effective in the treatment of advanced or metastatic non‐small cell lung cancer (NSCLC). However, whether the combination of PD‐1 inhibitors and antiangiogenic agents benefit advanced NSCLC patients as subsequent therapy remains unknown. In this study, we retrospectively reviewed the efficacy and safety profile of this combination strategy as subsequent therapy for NSCLC patients in a real‐world setting. Methods: A total of 30 patients with advanced NSCLC, who progressed after at least two cycles of platinum‐based chemotherapy or targeted therapy and subsequently received combination therapy with a PD‐1 inhibitor and antiangiogenic agent, were included in this study. The safety profile and efficacy were also investigated. Results: At the time of a median follow‐up period of 10.7 months, 28 patients had experienced progression of disease and 16 patients had died. The median progression‐free survial (mPFS) was 5.0 months (95% confidence interval [CI]: 3.179–6.821), and the median overall survival (mOS) was 14.3 months (95% CI: 8.912–19.659). The objective response rate (ORR) and the disease control rate (DCR) were 10.3% and 72.4%, respectively (0 complete remission, three partial responses and 18 stable disease in 29 patients with measurable lesions). Patients with PD‐L1 expression of at least 1% of tumor cells (n = 5) had relatively longer mPFS compared to those with PD‐L1‐negative tumors (n = 14), (11.6 months vs. 3.7 months). Treatment was suspended in two patients due to grade 3 immune‐related pneumonia and pancreatitis, respectively. No novel adverse events (AEs) or grade 4 AEs were observed. Conclusions: A combination of PD‐1 inhibitors and antiangiogenic targeting agents may be beneficial for patients with advanced or metastatic NSCLC as subsequent treatment, especially for patients with PD‐L1 protein expression positive, and treatment is well tolerated. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated the combination of epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) and other antitumor agents may delay drug resistance. In this study, we retrospectively reviewed the efficacy and safety of first‐line concurrent EGFR‐TKIs and platinum‐based doublet chemotherapy with or without an antiangiogenic agent for advanced lung adenocarcinoma patients in the real world. Methods: A total of 30 patients with advanced lung adenocarcinoma and activating EGFR mutations concurrently received an EGFR‐TKI and platinum‐based doublet chemotherapy with or without bevacizumab. The safety profile and efficacy were retrospectively reviewed. Results: At the median follow‐up time of 22.1 months, 18 patients had experienced disease progression, and six patients had died because of disease. The median progression‐free survival (mPFS) was 21.2 months (95% CI: 12.631–29.798). Of the 28 patients who had measurable lesions, the objective response rate and disease control rate were 71.4% and 96.4%, respectively (one patient achieved complete remission, 19 patients had a partial response and seven patients had stable disease). Male patients had significantly longer mPFS than female patients (32.6 vs. 14.6 months, HR = 3.593, 95% CI: 1.158–11.148, p = 0.027). The most frequently seen grade 3/4 adverse events were hematological toxicities, seen in three cases (10%). Three patients ceased bevacizumab due to vascular events, including hypertension (grade 2, 6.7%) and venous thrombosis (grade 2, 3.3%), and continued EGFR‐TKI and platinum‐based doublet chemotherapy. Conclusions: The combination of first‐generation EGFR‐TKIs with platinum‐based chemotherapy may be a first‐line treatment for advanced lung adenocarcinoma patients harboring activated EGFR mutations and is well tolerated. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is one of the most aggressive lung cancers. Treatment of SCLC has remained unchanged during the past decades. Preclinical studies have revealed ASCL1 as a transcription regulator in the neuroendocrine (NE) differentiation and carcinogenesis of SCLC. However, there are few studies on correlation of ASCL1 expression and clinicopathological factors in resected SCLCs. Here, we aimed to analyze the ASCL1 expression of SCLC and investigate its associations with clinicopathological factors and survival. Methods: A total of 247 surgically resected pure SCLC specimens were included in this retrospective study, all of which were processed using tissue microarrays for immunohistochemistry analysis of ASCL1. A total of 48 of 247 cases were tested by NanoString for mRNA expression analysis on 50 SCLC related genes. Statistical analysis was performed using R studio and SPSS software. Results: NE scores of 48 pure SCLC specimens were calculated by analyzing 50 preselected genes. A significant correlation between NE score with both ASCL1 mRNA expression and ASCL1 protein expression were observed. For the entire cohort of 247 patients, ASCL1 was highly expressed in 42.5% of pure SCLC patients according to IHC results. Significant differences were observed between ASCL1 high and low expression groups in variables including staging, lymph node metastasis, nerve invasion and overall survival. Conclusions: In limited staged pure SCLC, ASCL1 expression was positively correlated with NE signature, pTNM stage, nerve invasion and OS. ASCL1 may therefore serve as a potential biomarker to predict prognosis as well as in the selection of patients for therapies targeting ASCL1‐regulated downstream molecules. [ABSTRACT FROM AUTHOR]

Background: Histologically, SCLC are classified as pure (P‐SCLC) and combined subtypes (C‐SCLC). Currently, few studies compare the clinicopathological characteristics and explore the treatment strategies applied to them. Methods: Between July 2005 and April 2016, the clinical records of 297 postoperative patients with pathologically confirmed SCLC were retrospectively analyzed. Kaplan‐Meier method and Cox regression model were separately used for stratified univariate and multivariate survival analysis. Results: A total of 46 cases (15.5%) of C‐SCLCs and 251 cases (85.5%) of pure SCLCs (P‐SCLCs) were included in this study. The average age of C‐SCLCs was a little higher than that of P‐SCLCs (59.65 ± 8.72 vs. 56.56 ± 10.12; P = 0.053). More patients had a history of smoking in C‐SCLC (78.3% vs. 63.3%; P = 0.074). The five‐year overall survival (OS) rate for P‐SCLCs and C‐SCLCs was 65.1% and 56.7%, respectively (P = 0.683). For P‐SCLC, stage and an intervention of prophylactic cranial irradiation (PCI) were independent factors that affected OS. In C‐SCLCs cases, performing sublobectomy was an independent risk factor for poor prognosis. Conclusions: We identified no significant difference in clinical characteristics and outcome between C‐SCLCs and P‐SCLCs. However, the factors affecting the prognosis of the two subtypes were slightly inconsistent. For C‐SCLCs, the extent of resection had a greater impact on survival, and lobectomy combined with systemic lymph node dissection should therefore be performed as extensively as possible. In addition, PCI was beneficial in improving the SCLC OS rate. Key points: This study demonstrated the prognosis of C‐SCLCs did not significantly differ from that of P‐SCLCs, but was more susceptible to the extent of resection. Patients with C‐SCLC who underwent limited resection had a significantly increased risk of shorter OS.This study highlighted the importance of performing lobectomy for resectable C‐SCLC patients. This study also proved the benefit of PCI in improving the OS rate for both P‐SCLC and C‐SCLC patients. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐mutation or anaplastic lymphoma kinase (ALK)‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear. Methods: We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb–IV) at 12 Chinese hospitals. Results: The most common evaluation methods were amplification‐refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non‐squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2–2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3–2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4–10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1–2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7–4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR‐positive patients and 51.4% in ALK‐positive patients. There was a negative correlation between the first‐line targeted therapy rate and the EGFR mutation detection period (r = −0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = −0.179, P = 0.076). Conclusion: Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first‐line targeted therapy rate remains low in Chinese patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: Afatinib is an irreversible ErbB family blocker that improves progression‐free survival (PFS) of advanced EGFR‐mutant lung adenocarcinoma compared to chemotherapy. However, afatinib leads to more adverse events than first‐generation EGFR inhibitors. Hence, exploration of the optimal afatinib initial dose and its efficacy and safety in Asian patients has drawn extensive attention. Methods: We retrospectively evaluated demographic and clinical information, survival data, and adverse events in advanced non‐small cell lung cancer patients treated with afatinib from 27 February 2017 to 30 October 2018. Results: A total of 60 patients were included in the study. Thirty‐nine (65%) patients received afatinib as first‐line treatment. The median PFS was 12.3 months (95% confidence internal 7.6–17.0). Multivariate Cox regression analysis revealed that age, gender, smoking history, baseline brain metastasis status, afatinib starting dose, and mutation type did not significantly influence PFS. No significant difference in median PFS between patients treated with an initial dose of afatinib of 40 mg or 30 mg, either in the first‐line (14.5 vs. 5.2 months; P = 0.101) or in a second or later‐line setting (3.0 vs. 5.0 months; P = 0.375) was observed. The incidence of all grades of rash/acne (92.5% vs. 61.1%; P = 0.011) and paronychia (82.5% vs. 50.0%; P = 0.010) in the 40 mg group was significantly higher than in the 30 mg group. Conclusion: First‐line afatinib treatment is beneficial for advanced lung adenocarcinoma patients with sensitive EGFR mutations. Initial dose and baseline brain metastasis status do not significantly impact PFS. [ABSTRACT FROM AUTHOR]

Background: Crizotinib is associated with a favorable survival benefit in patients with ALK‐positive non‐small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response. Methods: We collected the clinical features and survival outcomes of 28 primary‐resistant responders (PRR) with progression‐free survival (PFS) of < 3 months on crizotinib and compared these with 78 long‐term responders (LTR) that achieved > 24 months PFS (control). Results: Primary resistance was observed in 6.5% of the patients. The median PFS of the PRR and LTR groups was 1.2 months (95% confidence interval [CI] 0.70–1.73) and 47.0 months (95% CI 34.39–59.64), respectively. A better Eastern Cooperative Oncology Group performance status score was significantly associated with longer PFS (odds ratio 0.06, 95% CI 0.01–0.33; P = 0.001). The median overall survival (OS) of the PRR group was 8.4 months (95% CI 3.47–13.42) and crizotinib as first‐line treatment was an independent predictive factor for survival outcome (P = 0.005). Patients administered ALK‐tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK‐tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944). Conclusion: Patients with primary resistance to crizotinib displayed unfavorable survival outcomes and the underlying mechanism cannot be identified in clinical features. Nevertheless, next‐generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population. [ABSTRACT FROM AUTHOR]

Background: Crizotinib has demonstrated favorable efficacy in patients with advanced ALK‐positive non‐small cell lung cancer (NSCLC). Unfortunately, the majority of ALK‐positive patients ultimately develop acquired resistance within one year after the initiation of crizotinib treatment; however, the estimation of overall survival (OS) beyond crizotinib resistance has not yet been fully demonstrated. The purpose of this study was to identify favorable predictors affecting survival outcome. Methods: In this single‐center retrospective study, the data of 136 patients with advanced ALK‐positive NSCLC beyond crizotinib resistance were analyzed between January 2013 and December 2017. Patients were divided into two groups according to intracranial or extracranial progression on crizotinib, and sequential therapies including crizotinib continuation with local therapy, next‐generation ALK inhibitors, and chemotherapy. The primary endpoint was the median OS duration from the start of crizotinib resistance to death or the last follow‐up. Univariate and multivariate Cox analyses of OS were carried out. Results: At the time of analysis, 60 (41.1%) of the 136 patients had died. Median progression free survival (PFS) and OS from the metastatic diagnosis were 10.4 and 41.3 months, respectively. Sequential therapies administered beyond crizotinib treatment were: next‐generation ALK inhibitors (54 patients), chemotherapy (20 patients), and crizotinib continuation with local therapy (62 patients). Multivariate Cox analysis revealed that long PFS with crizotinib (≥ 10.4 months), intracranial progression, and next‐generation ALK inhibitors were significantly associated with a decreased risk of death. Conclusion: Long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next‐generation ALK inhibitors might be favorable predictors for OS in advanced ALK‐positive NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab (Bev) plus platinum‐based chemotherapy is a standard first‐line treatment option for advanced non‐squamous non‐small cell lung cancer (NS‐NSCLC). We evaluated the efficacy and safety of continuing Bev in Chinese patients with advanced NS‐NSCLC progression after first‐line treatment containing Bev in a real‐world setting. Methods: The data of 118 patients with advanced NS‐NSCLC who received Bev between July 2009 and July 2017 were retrospectively collected. The patients were divided into groups: 15 in Bev first‐line, 82 in Bev ≥ second‐line, and 21 in Bev cross‐lines. The primary endpoint was overall survival; secondary objectives were progression‐free survival, objective response rate, disease control rate, and safety. Results: The overall survival was 21.8, 32.5, and 18.9 months (P = 0.092) in the overall population and 39.3, 25.8, and 15.0 months (P = 0.347) in the wild‐type population in the Bev first‐line, Bev ≥ second‐line, and Bev cross‐lines groups, respectively. There were no significant differences in progression‐free survival of second‐line treatment between the groups in the overall population: 2.6, 3.7, and 3.2 months in the Bev first‐line, Bev ≥ second‐line, and Bev cross‐lines groups, respectively (P = 0.796). No statistically significant improvement in objective response or disease control rates in the Bev cross‐lines group was observed. No unexpected or severe adverse events were recorded. Conclusion: We found no benefit in continuing Bev treatment beyond progression after first‐line treatment containing Bev for patients with advanced NS‐NSCLC. Further research of validated predictive biomarkers of response to treatment after long‐term antiangiogenic therapy is required. [ABSTRACT FROM AUTHOR]

The CAPTRA‐Lung study (NCT03334864) is a prospective observational study that will capture real‐world data of patients with advanced or metastatic non‐small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow‐up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression‐free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub‐cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research. [ABSTRACT FROM AUTHOR]

Background: Before tyrosine kinase inhibitor (TKI) therapy can be administered in patients with advanced non‐small cell lung cancer (NSCLC), EGFR mutation testing is required. However, few studies have evaluated the extent of EGFR testing in real‐world practice in China. Methods: A multicenter, observational study of EGFR testing in NSCLC patients in North China was conducted. Treatment‐naïve patients or those with postoperative recurrent stage IIIB/IV NSCLC were enrolled. The primary objective was EGFR testing rate. Secondary objectives included EGFR mutation status, EGFR testing methods and specimens, factors associated with EGFR testing, and overall survival with or without EGFR testing. Results: Overall, 2809 patients with stage IIIB/IV NSCLC were enrolled; 90.78% had adenocarcinoma. The EGFR screening rate was 42.54%. EGFR testing rates were higher in tumor samples obtained by lymph node puncture, and in patients with urban medical insurance, adenocarcinoma, non‐smokers, or those located in developed cities (all P < 0.001). The EGFR mutation rate was 46.44%. The most commonly used specimens for EGFR testing were biopsy tumor samples (67.53%). PCR‐based methods (72.05%), Sanger sequencing (5.36%), and Luminex liquid chip (5.10%) were the most frequently used testing platforms. Similar positive EGFR mutation rates were achieved with different platforms. TKI therapy was the first‐line treatment administered to most EGFR‐positive patients (56.22%), and chemotherapy in EGFR‐negative patients (84.88%). Overall survival was higher in EGFR‐tested than in untested patients (27.50 vs. 19.73 months; P = 0.007). Conclusion: Real‐world EGFR testing rates for NSCLC in North China were relatively low because of clinical and social factors, including medical insurance coverage. [ABSTRACT FROM AUTHOR]

Background: Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non‐small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first‐line regimen containing bevacizumab (B+) versus a non‐bevacizumab regimen (non‐B) in advanced non‐squamous NSCLC (NS‐NSCLC) patients in a real world setting. Methods: The medical records of patients with advanced NS‐NSCLC who received first‐line therapy with or without bevacizumab were retrospectively collected. The primary outcome was progression‐free survival (PFS), with secondary objectives of objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analysis of EGFR and ALK status was conducted in subgroup. Results: One hundred and forty‐nine patients met the selection criteria: 62 in the B+ and 87 in the non‐B group. The baseline characteristics were well balanced. In the overall population, the median PFS was significantly longer in the B+ than in the non‐B group (9.7 vs. 7.0 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.30–0.91; P = 0.0184). Improved trends in both ORR and DCR were observed in the B+ group. In wild‐type patients, the median PFS of the B+ was 11.3 compared to 5.5 months in the non‐B group (HR 0.43, 95% CI 0.20–0.91; P = 0.0234). In wild type and unknown populations, the median PFS was 11.3 (B+) compared to 6.0 months (non‐B) (HR 0.53; 95% CI 0.28–1.02; P = 0.0520). The safety profile was acceptable in both groups and no unexpected findings were observed. Conclusion: Our analysis confirmed that a first‐line regimen containing bevacizumab showed superior clinical benefits over a non‐bevacizumab regimen in Chinese patients with advanced NS‐NSCLC in a real world setting. [ABSTRACT FROM AUTHOR]

Background: EGFR‐tyrosine kinase inhibitors (TKIs) combined with TS‐1 might overcome EGFR‐TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR‐TKIs and TS‐1 in non‐small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR‐TKI therapy. Methods: This was a phase II, single‐arm and single‐center prospective study. Stage IIIB–IV NSCLC patients with acquired resistance to prior EGFR‐TKI treatment were enrolled. All patients were administered combination therapy of TS‐1 and continuing EGFR‐TKIs in this study. The primary endpoints were progression‐free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints. Results: A total of 42 patients with acquired resistance to EGFR‐TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6–5.4). The OS and DCR were 31.9 (95% CI 17.8–46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin. Conclusion: The combination treatment of TS‐1 and EGFR‐TKIs was effective and well tolerated by patients who had experienced prior EGFR‐TKI treatment failure. Our results need to be validated by larger prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: To investigate the correlation between mesenchymal–epithelial transition factor (C‐Met) and human epidermal growth receptor 2 (HER2) protein expression in primary lung adenocarcinoma tissues. Method: A total of 1479 resected primary lung adenocarcinoma patients were enrolled in the present study for detecting of C‐Met and HER2 protein by immunohistochemistry, and correlation analysis was made between the above two biomarkers and related clinicopathological features. Result: Both C‐Met and HER2 proteins were found to stain highly positive in lung adenocarcinomas, and a positive correlation was found between them (χ2 = 118.5, P = 2.707 × 10−21). In addition, HER2 protein expression was correlated with sex, pathological stage, lymph node metastasis, and major subtypes; and C‐Met was correlated with sex (P < 0.05). Conclusion: The expression of C‐Met and HER2 protein in lung adenocarcinoma is highly correlated, and whether it is synergistic in the targeted therapy of lung adenocarcinoma deserves further study. [ABSTRACT FROM AUTHOR]

Osimertinib is a novel, irreversible, mutant‐selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations and the EGFR T790 mutation. Here, we report a woman with EGFR‐mutated lung adenocarcinoma who, after 23‐month treatment with gefitinib, developed the EGFR T790M mutation, which converted the T790M status from positive to negative before osimertinib treatment and developed MET amplification, leading to rapid progression on osimertinib in two months. Subsequent treatment with crizotinib and c‐Met inhibitor plus gefitinib also failed to improve the clinical outcome, suggesting the potential existence of another resistance mechanism. Our findings revealed the underlying multiple and heterogeneous mechanisms in resistance to osimertinib, suggesting combination strategies should be considered post‐osimertinib progression. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the application of actual carboplatin in carboplatin plus pemetrexed regimen as first‐line treatment for advanced lung adenocarcinoma, and to determine the recommended dose of carboplatin for Chinese populations. Methods: From January 2014 to April 2016, 151 advanced lung adenocarcinoma patients who received carboplatin and pemetrexed (500 mg/m2) were included. The area under the curve (AUC) of carboplatin was back‐calculated from actual dosages using the Calvert formula. According to the median of calculated AUC, patients were divided into AUC ≥4 and <4 groups. Results: The median of AUC was 4 (1.8–5.5). A total of 79 patients had an AUC ≥4 and 72 patients had an AUC <4. The mean relative dose intensities of pemetrexed were 100.4% for the AUC ≥4 group, and 101.4% for <4 group. Baseline characteristic variables were balanced between the two groups, except for Eastern Cooperative Oncology Group Performance score (P = 0.044). The overall response rate (ORR) and disease control rate (DCR) were 33.8% and 90.1%, respectively, 35.4% and 86.1% for the AUC ≥4 group, and 31.9% and 94.4% for the AUC <4 group. No significant difference was observed in ORR (P = 0.650) and DCR (P = 0.086) between the two groups. Conclusion: Compared with an AUC of 5 or 6, the actual clinical application of AUC was generally insufficient for Chinese populations; fortunately, therapeutic efficacy remained equal. We found that AUC <4 was as adequate as AUC ≥4 in pemetrexed plus carboplatin regimen as first‐line treatment for them. [ABSTRACT FROM AUTHOR]

Background This study was conducted to evaluate the value of gemcitabine combined with cisplatin as adjuvant chemotherapy for radical resection of non-small cell lung cancer. Methods Data of 100 patients who had undergone radical resection of non-small cell lung cancer and were treated with cisplatin/gemcitabine as adjuvant chemotherapy between June 2007 and December 2010 at the Chinese Academy of Medical Sciences were reviewed. Results The median age was 59 years (range 36-73); 82% of the patients were male. Forty-two percent had adenocarcinoma and 55% had squamous cell carcinoma. Most patients had pathologic IIB (29%) and IIIA (44%) stage disease. Eighty-five percent of patients completed four cycles of chemotherapy, with 76% completing the planned full dose. The main reason for a reduced gemcitabine dose in 13 patients was grade 3/4 neutropenia or thrombocytopenia. The median dose and dose intensity were 8377.1 mg/m2 and 708 mg/(m2/week) for gemcitabine and 293.38 mg/m2 and 25.24 mg/(m2/week) for cisplatin, respectively. During follow-up the median disease-free survival was 33.8 months (95% confidence interval [ CI] 15.938-51.676). Patients with squamous cell carcinoma (hazard ratio [ HR] 0.404, 95% CI 0.241-0.676; P = 0.001) and pathologic stage I ( HR 4.379, 95% CI 1.721-11.142; P = 0.002) achieved better disease-free survival. The survival rates at one, two, and five years were 94%, 77%, and 55%, while the survival rates without recurrence were 64%, 53%, and 39%, respectively. Conclusion As an adjuvant chemotherapy regimen, gemcitabine with cisplatin is well tolerated. Patients with squamous cell carcinomas or pathologic stage I achieve better results. [ABSTRACT FROM AUTHOR]

Background: The efficacy of pemetrexed-based first-line chemotherapy in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. Methods: The clinicopathological characteristics and treatment outcomes of 52 patients with ALK-positive advanced NSCLC who received pemetrexed as first-line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression-free survival (PFS). Results: The gender proportion was balanced and the median age was 51 years (range 26-76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454-11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. Conclusions: Pemetrexed is efficient and tolerated as first-line treatment for ALK-positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK-positive NSCLC. [ABSTRACT FROM AUTHOR]

Background The aim of the study was to characterize the histological and epidemiological features of lung cancer in Chinese women. Methods Demographic and histological information on female lung cancer cases identified during 1 January 2000 through 31 December 2012 from the Cancer Hospital of the Chinese Academy of Medical Sciences were collected. The International Classification of Diseases for Oncology system was used to classify the histological subtypes. Relative frequencies ( RF) were estimated for major histological subtypes and compared by the years of diagnosis and birth, and among residential areas. Statistical differences were tested for RFs in the time periods with a trend test and with Pearson Chi square tests for distribution. Results Of 7070 female Chinese lung cancer cases, the major histological subtypes were adenocarcinoma ( ADC) 65.79%; squamous cell carcinoma ( SCC) 10.21%; small cell cancer 8.12%; large cell carcinoma, 2.79%; and adeno-squamous carcinoma ( ASC), 2.19%. ADC increased, with RFs from 46.72% in the cases identified in 2000-2002 to 76.49% in 2011-2012 ( Z = 16.998, P < 0.0001); SCC decreased from 15.69% to 5.97% ( Z = −8.750, P < 0.0001). Compared to the cases identified in 2000-2006, the age-adjusted RFs of ADC in 2007-2012 consistently increased in all study areas. Conclusion The significant increase of ADC of the lung in Chinese women suggests that a persistently strong exposure to potential carcinogens in the Chinese population should be further and fully investigated. [ABSTRACT FROM AUTHOR]

Background This study was conducted to evaluate the efficacy and safety of paclitaxel-carboplatin combined with intercalated gefitinib in patients with advanced, untreated, nonsquamous non-small cell lung cancer. Methods A total of 29 patients were enrolled in the study. All patients were Chinese, with a histology type of adenocarcinoma, without a smoking history, and as a result of the limited tissue sample, an epidermal growth factor receptor ( EGFR) mutation test could not be performed. All patients received chemotherapy of paclitaxel-carboplatin every 21 days for four cycles, and gefitinib (250 mg/day) was administered on days eight to 17 of the chemotherapy cycle. If the patient responded to chemotherapy, maintenance therapy of 250mg of gefitinib could be administered daily. Results All of the 29 patients received at least one cycle of chemotherapy and gefitinib, and 25 patients received four cycles of therapy. Eighteen patients selected maintenance therapy with gefitinib. The objective response rate was 74.1% (95% confidence interval, 53.7% to 88.9%). No complete response was achieved. The median progression-free survival was 16 months, however, the median overall survival was not available by the conclusion of the study. The major adverse event was hematologic toxicity. Conclusions The regimen of paclitaxel-carboplatin combined with intercalated gefitinib showed a high response rate and a favorable safety profile. Gefitinib maintenance therapy was proven to be beneficial. This study proposes a good pattern of chemotherapy combined with EGFR tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]