Benefit Of Tyrosine Kinase Inhibitors Research Articles

Erlotinib en 2e ou 3e ligne pour les cancers bronchiques non à petites cellules sans mutation de l’EGFR : données en vie réelle

The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial. The survival of patients with an EGFR wild-type NSCLC who received second- or third-line erlotinib treatment was assessed using real-life data that had been collected in a prospective, national, multicenter, non-interventional cohort study. Data from 274 patients were analysed, 185 (68%) treated with erlotinib and 89 (32%) treated with supportive care only. The median overall survival was 4.2months (95% CI [3.5; 5.4]) with erlotinib, and 1.3months (95% CI [1.0; 1.8]) with supportive care. Survival rate at 3, 6, and 12months was 62%, 37%, and 17%, respectively, with erlotinib, versus 20%, 8%, et 3%, with exclusive supportive care. Significant predictive factors for longer overall survival were the presence of adenocarcinoma, and use of 1st line chemotherapy including either taxanes, pemetrexed or vinorelbine (P<0.05). Erlotinib remains a valuable therapeutic option to treat inoperable locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen in fragile patients who are not eligible for chemotherapy.

Metabolic reprogramming and redox adaptation in sorafenib-resistant leukemia cells: detected by untargeted metabolomics and stable isotope tracing analysis

BackgroundInternal tandem duplications (ITD) within the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3) represent a poor prognostic indicator in acute myeloid leukemia (AML). Therapeutic benefits of tyrosine kinase inhibitors, such as sorafenib, are limited due to the emergence of drug resistance. While investigations have been conducted to improve the understanding of the molecular mechanisms underlying the resistance to this FLT3 inhibitor, a profile of cell functioning at the metabolite level and crosstalk between metabolic pathways has yet to be created. This study aimed to elucidate the alteration of metabolomic profile of leukemia cells resistant to the FLT3 inhibitor.MethodsWe established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, namely the murine BaF3/ITD-R and the human MV4-11-R cell lines. We performed a global untargeted metabolomics and stable isotope-labeling mass spectrometry analysis to identify the metabolic alterations relevant to the therapeutic resistance.ResultsThe resistant cells displayed fundamentally rewired metabolic profiles, characterized by a higher demand for glucose, accompanied by a reduction in glucose flux into the pentose phosphate pathway (PPP); and by an increase in oxidative stress, accompanied by an enhanced glutathione synthesis. We demonstrated that the highest scoring network of altered metabolites in resistant cells was related to nucleotide degradation. A stable isotope tracing experiment was performed and the results indicated a decrease in the quantity of glucose entering the PPP in resistant cells. Further experiment suggested that the inhibition of major enzymes in the PPP consist of glucose-6-phosphate dehydrogenase deficiency (G6PD) in the oxidative arm and transketolase (TKT) in the non-oxidative arm. In addition, we observed that chronic treatment with sorafenib resulted in an increased oxidative stress in FLT3/ITD-positive leukemia cells, which was accompanied by decreased cell proliferation and an enhanced antioxidant response.ConclusionsOur data regarding comparative metabolomics characterized a distinct metabolic and redox adaptation that may contribute to sorafenib resistance in FLT3/ITD-mutated leukemia cells.

&lt;p&gt;The efficacy and safety of apatinib in metastatic alveolar soft part sarcoma: a case series of six patients in one institution&lt;/p&gt;

Background: Evidence suggests that advanced or metastatic alveolar soft part sarcoma (ASPS) with high metastatic potential is chemo-resistant. However, the benefits of tyrosine kinase inhibitors have been demonstrated for the treatment of ASPS.Purpose: This study aimed to investigate the efficacy and safety of apatinib, aspecific VEGFR-2 inhibitor, in ASPS patients. This retrospective analysis involved six patients with metastatic ASPS not amenable to curative treatment.Patients and methods: Apatinib was administered at a dose of 500mg per day. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines. Survival analysis was performed using the Kaplan–Meier test, and a safety profile was recorded.Results: The mean age of patients was 26.5 (range, 17–32) years. The median progression-free survival (PFS) was 18.53 months (95% CI, 12.23-NE). However, median overall survival (OS) has not been reached. Twenty-four month PFS and OS rates were 50.0% and 100.0%, respectively. One patient achieved a complete response, and the remaining patients achieved partial responses, with an objective response rate of 100%. Median follow-up was 20.6 (range, 12.43–34.13) months. The most common adverse events included gastrointestinal discomfort (4/6[66.7%]), hair hypopigmentation (4/6[66.7%]) and hand-foot skin reaction (3/6[50.0%]).Conclusion: Apatinib shows beneficial activity in metastatic ASPS patients, and further studies are warranted with more cases and longer follow-up periods to fully characterize clinical efficacy and safety of apatinib in ASPS.

Current perspectives for the treatment of chronic myeloid leukemia

With an annual incidence of 1–2 in a million, Ph*(+) chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disease that makes myeloid neoplastic cells breed out of control. This BCR-ABL(+) myeloproliferative disease makes up about 15%–20% of all leukemia cases in adults. CML is seen more in males than females, with a rate of three to two. However, it does not show differences in prevalence in terms of age. CML consists of three clinical phases. The first one is the chronic phase, defined by rising white blood cell levels and also by myeloid proliferation and bone marrow maturation. While this phase does not exhibit complications, in diagnosis, it comprises most of the patients. The second phase is the accelerated phase, which the disease progresses to if it is not treated or does not respond to treatment. This usually takes about 3 years. The third phase is the blastic phase. The chronic phase can still progress to the next two phases within the first 2 years, with a rate of 10%. In the following years, the possibility increases by 15%–20% each year. Tyrosine kinase inhibitors (TKIs) are revolutionary drugs for the management of disease course in CML. The aim of this review is to assess current approaches to CML patients’ follow-up and treatment with TKIs. A literature search on CML and TKIs was made in PubMed, Web of Science, and Scopus with particular focus on randomized clinical trials, recommendations, guidelines, and expert opinions. In managing CML, various treatment methods have been utilized for many decades. Prior to the development of TKIs, interferon alpha was the primary tool, which was then complemented by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was successful in slowing the disease down in the long term and curing up to 50% of patients. Then the coming of the imatinib era opened up different treatment perspectives. For the patients resistant or intolerant to imatinib, second- and third-generation TKIs are successfully used in distinct CML disease states. The survival benefits of TKIs including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib for CML patients are outstanding. TKI-related adverse events could impact the clinical course, especially in long-term drug administrations. The current aim for CML disease management in the TKI era is to provide age- and sex-matched normal life duration to CML patients.

Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma

BackgroundNivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. MethodsMedical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. ResultsOverall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19–NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5–13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5–16] and 7 months (5–NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (≥6 months) with 8 versus 5 months for short responder (<6 months) (p = 0.03). OS rate was 54% at 12 months. Toxicity was as expected: 42% developed at least one toxicity grade ≥3. ConclusionThis is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence.

Transporter and Lysosomal Mediated (Multi)drug Resistance to Tyrosine Kinase Inhibitors and Potential Strategies to Overcome Resistance.

Tyrosine kinase inhibitors are a class of chemotherapeutic drugs that target specific protein kinases. These tyrosine kinase inhibitors constitute a relatively new class of drugs which target for instance Bcr-Abl, Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR). Despite some initial successes, the overall therapeutic benefit of tyrosine kinase inhibitors in the clinic has been mixed. Next to mutations in the target, multidrug resistance is a major obstacle for which still no clinically effective strategies have been developed. Major mechanisms of multidrug resistance are mediated by drug efflux transporter proteins. Moreover, there is accumulating evidence that multidrug resistance can also be caused by lysosomal sequestration of drugs, effectively trapping tyrosine kinase inhibitors and preventing them from reaching their target. Lysosomal drug sequestration seems to work together with ATP-binding cassette transporters, increasing the capacity of lysosomes to mediate sequestration. Both membrane efflux transporter proteins and lysosomes present potential therapeutic targets that could reverse multidrug resistance and increase drug efficacy in combination therapy. This review describes both mechanisms and discusses a number of proposed strategies to circumvent or reverse tyrosine kinase inhibitor-related multidrug resistance.

Detection of oligoprogressive disease in oncogene-addicted non-small cell lung cancer using PET/CT versus CT in patients receiving a tyrosine kinase inhibitor

Objectives: In oncogene-addicted non-small cell lung cancer (NSCLC), oligoprogressive disease (OPD) can be treated with local ablative therapy (LAT) to prolong benefit from tyrosine kinase inhibitors (TKIs). A comparison of PET/CT vs. CT for the detection of OPD at first extra central nervous system (eCNS) progression was performed to determine which modality was more sensitive for OPD detection.Materials and methods: Patients with metastatic EGFR-MT, ALK + or ROS-1+ NSCLC on a relevant TKI from 2010 to 2016 were identified. Scan methodology at first eCNS progression (index scan) was noted and progression was categorized as OPD (≤ 4 lesions) or non-OPD (> 4 lesions).Results: Of the 67 analyzable patients (EGFR-MT = 37, ALK+ = 28, ROS1+ = 2), OPD was detected in 81.3% (26/32) by PET/CT vs. 68.6% (24/35) by CT (p = 0.363). Of these, 17/26(65.4%) in PET/CT and 5/24(20.8%) in CT group had LAT (p = 0.004). Among patients receiving an alternate modality scan within 6 weeks of the index scan that showed first eCNS progression, 91.7% (11/12) had CT prior to index PET/CT, 75% (6/8) had post-index PET/CT showing further progression, whereas 0% (0/5) had post-index CT showing further progression. Time to progression (TTP), Post-progression TKI benefit (TTP2) and overall survival (OS) were longer in the PET/CT-detected group (p = 0.001, p = 0.032, and p = 0.01, respectively). In both PET/CT (N = 26) and CT-detected (N = 24) OPD subgroups, TTP2 and OS were longer in those that received LAT (65.4% [17/26] and 20.8% [5/24]) versus those that did not, although the difference was not statistically significant.Conclusion: PET/CT demonstrated a non-significant trend to detect more eCNS OPD and a significantly higher rate of OPD suitable for LAT than CT. Peri-progression alternate modality scans were also consistent with PET/CT being more sensitive. A prospective randomized study is required to assess the long-term impact of PET/CT vs CT in oncogene-addicted NSCLC patients on TKI therapy.

Tumor-infiltrating neutrophils predict therapeutic benefit of tyrosine kinase inhibitors in metastatic renal cell carcinoma

ABSTRACT Tumor-infiltrating neutrophils (TINs) show diverse predictive effects in the context of different cancer types and therapeutic regimens. In this study we investigated their relevance with therapeutic effect of tyrosine kinase inhibitors (TKIs) in metastatic renal cell carcinoma (mRCC). Two independent datasets including 271 mRCC patients treated by TKIs or IL-2/IFN-α based immunotherapy were retrospective included, and TINs were detected by immunohistochemistry. The presence of TINs was observed in 50 (45.0%) samples of the TKI cohort and in 73 (45.6%) samples of the immunotherapy cohort. TINs were associated with shorter overall survival (HR, 1.776; 95%CI, 1.191–2.650; p = 0.004) in the TKI cohort, but not in the immunotherapy cohort (HR, 1.074; 95%CI, 0.767–1.505; p = 0.672). Multivariate Cox analysis confirmed the independent prognostic value of TINs for TKI-treated patients (HR, 2.078, 95%CI, 1.352–3.195; p = 0.001), apart from other parameters. Moreover, survival benefit of TKI therapy was superior to IL-2/IFN-α immunotherapy only among TINs-absent patients (HR, 1.561; 95%CI, 0.927–2.629; p = 0.094). Data mining in the TCGA cohort of renal cell carcinoma revealed the predominant immunosuppressive function of TINs in renal cell carcinoma. The negative correlation between TINs and intratumoral CD8+ T cells was further confirmed in the TKI cohort (p = 0.019), the immunotherapy cohort (p = 0.001) and the TCGA cohort (p < 0.001). In conclusion, the presence of TINs was an independent, unfavorable prognostic factor in TKI-treated mRCC patients. TINs could also predict therapeutic benefit of TKIs over IL-2/IFN-α immunotherapy. These findings should be further confirmed within datasets of clinical trials or prospective observational studies.

Clinical Status and Treatment of Liver Metastasis of Differentiated Thyroid Cancer Using Tyrosine Kinase Inhibitors.

Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs. We retrospectively analyzed clinical features of 29 patients (mean age 67.8years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017. All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively. Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

Tumor-infiltrating neutrophils predict therapeutic benefit of tyrosine kinase inhibitors in metastatic renal cell carcinoma

Tumor-infiltrating neutrophils (TINs) show diverse predictive effects in the context of different cancer types and therapeutic regimens. In this study we investigated their relevance with therapeut...

Kidney Cancer Research Network of Canada consensus statement on the role of adjuvant therapy after nephrectomy for high-risk, non-metastatic renal cell carcinoma: A comprehensive analysis of the literature and meta-analysis of randomized controlled trials.

The Kidney Cancer Research Network of Canada (KCRNC) collaborated to prepare this consensus statement about the use of target agents as adjuvant therapy in patients with non-metastatic renal cell carcinoma (nmRCC) after nephrectomy. We reviewed the published data and performed a meta-analysis of studies that focused on vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). A systematic literature search identified seven trials on adjuvant target therapy in nmRCC. Three trials, the ASSURE, S-TRAC, and PROTECT, focused on VEGFR TKIs and represented the focus of the study, including a meta-analysis combining their data on disease-free survival (DFS) and overall survival (OS). The ASSURE trial showed no DFS or OS benefit of TKIs over placebo after one year of adjuvant sorafenib or sunitinib. In contrast, the S-TRAC trial showed improved DFS after one year of adjuvant sunitinib using central review process, but not using investigator review process. No OS benefit was recorded in either study. Recently, the PROTECT trial also showed no DFS or OS benefit when one year of adjuvant pazopanib was compared to placebo. Meta-analyses of the pooled DFS and OS estimates from all three trials resulted in DFS and OS hazard ratios of 0.87 (95% confidence interval [CI] 0.73-1.04) and 1.04 (95% CI 0.89-1.22), respectively. Data from three available clinical trials of adjuvant VEGFR TKIs vs. placebo do not currently support the use of adjuvant TKI therapy as standard of care after nephrectomy for nmRCC. At this time, adjuvant TKI-based adjuvant therapy is not recommended for routine use after nephrectomy for high-risk nmRCC, but highly motivated patients may benefit from a discussion with their oncologist regarding the risks and benefits of adjuvant TKI.

Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer.

Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. Patients and Methods We identified 129 patients with ALK-positive NSCLC with known ALK variants. ALK resistance mutations and clinical outcomes on ALK TKIs were retrospectively evaluated according to ALK variant. A Foundation Medicine data set of 577 patients with ALK-positive NSCLC was also examined. Results The most frequent ALK variants were EML4-ALK variant 1 in 55 patients (43%) and variant 3 in 51 patients (40%). We analyzed 77 tumor biopsy specimens from patients with variants 1 and 3 who had progressed on an ALK TKI. ALK resistance mutations were significantly more common in variant 3 than in variant 1 (57% v 30%; P = .023). In particular, ALK G1202R was more common in variant 3 than in variant 1 (32% v 0%; P < .001). Analysis of the Foundation Medicine database revealed similar associations of variant 3 with ALK resistance mutation and with G1202R ( P = .010 and .015, respectively). Among patients treated with the third-generation ALK TKI lorlatinib, variant 3 was associated with a significantly longer progression-free survival than variant 1 (hazard ratio, 0.31; 95% CI, 0.12 to 0.79; P = .011). Conclusion Specific ALK variants may be associated with the development of ALK resistance mutations, particularly G1202R, and provide a molecular link between variant and clinical outcome. ALK variant thus represents a potentially important factor in the selection of next-generation ALK inhibitors.

AGS-003 combined with sunitinib for the precision treatment of metastatic renal cell carcinoma

ABSTRACTIntroduction: Unselective approaches of immunotherapy in metastatic renal cell cancer (mRCC) have been largely abandoned over the past decade. Despite the established clinical benefit of tyrosine kinase inhibitors for mRCC and the recent successful implementation of immune check-point inhibition, specific immunotherapy may additionally contribute to anti-cancer immune response with good tolerability and long-term clinical benefit.Areas covered: AGS-003 represents an approach of specific immunotherapy using a dendritic cell-based vaccine based on monocyte derived dendritic cells, which are co-electroporated with individual antigen coding amplified tumor RNA and synthetic CD40L RNA. After successful clinical phase I and II trials, current evaluation of AGS-003 in mRCC in combination with sunintib is under way in a phase III clinical trial and results are awaited.Expert commentary: Initial results from clinical evaluation of AGS-003 are promising also based on the underlying mechanistic rationale. Toxicity profiles in combinatory regimens are mainly attributed to the side effects of the respective drugs. Apart from further awaited results of the oncologic efficacy of AGS-003 in mRCC, it will be of interest how the preparation of the compound ex vivo and issues related to cost and logistics will affect a potential clinical application of AGS-003 in the daily routine practice.

Development and validation of a predictive score, for identifying poor eastern cooperative oncology group performance status (performance status 3-4) advanced nonsmall cell lung cancer patients who are likely to benefit from tyrosine kinase inhibitors.

One of the ten advanced lung cancer patients presents with poor eastern cooperative oncology group performance status (ECOG PS). There are no clear guidelines about management of these patients. The benefit of tyrosine kinase inhibitors (TKI) in this patient population remains questionable. Hence, in this study, we attempted to develop and validate a predictive score which would predict benefit from oral TKI. This was a prospective observational study done at Tata Memorial Hospital, India. Patients with nonsmall cell lung cancer with ECOG PS 3-4 were included in this study. All these patients had received oral TKI on compassionate grounds and were followed up till death. The overall survival (OS) was calculated from date of start of TKI to date of death. R software was used for development and validation of the predictive model. The median survival duration of the discovery cohort and validation cohort were 170.5 and 115 days, respectively. The model predicted OS accurately, within ±2 months in 72.1% and within ±3 months in 81.7% of patients. The current model can predict OS in poor PS patients treated with TKI within a satisfactory clinical range and can be used for decision-making of these patients.

Detection of novel polymorphisms in the ckit gene of canine patients with lymphoma, melanoma, haemangiosarcoma, and osteosarcoma.

Tyrosine kinase inhibitors (TKIs) that specifically target cKIT represent a therapeutic approach for non-resectable canine mast cell tumours (MCTs) grade II/III. The therapeutic benefit of TKIs has been investigated in other tumours based on clinical response rates and identification of gain-of-function mutations. In the present study, cKIT expression in 14 dogs with osteosarcoma, melanoma, haemangiosarcoma, lymphoma, and fibrosarcoma was analysed. Tissue samples were used for cKIT sequencing to (I) detect the cKIT transcript and to (II) identify gain-of-function mutations. The cKIT transcript was detected in ten patients. Four novel amino acid substitutions and five silent polymorphisms were identified. Furthermore, an insertion mutation (GNSK) was discovered in the tissue, but not in the blood sample of one dog. CKIT expression was identified in a variety of canine tumours and, therefore, TKIs might have a broader therapeutic indication apart from treatment of MCTs. Further investigations will be necessary to localize the cKIT protein in the respective tumours and to evaluate the functional consequence of the cKIT variants identified in the present study.

Chimiothérapie périopératoire du cancer bronchique non à petites cellules (CBNPC) vue par le chirurgien

IntroductionUp to now, surgery remains the treatment of choice for early-stage nonsmall cell lung cancer. However, despite surgery with curative intent, risk of recurrence and cancer-related deaths are major concern. State of the artUse of adjuvant chemotherapy is supported by evidences in stages II and III, however more controversial in stage IB. Published meta-analyses have reached conclusion that adjuvant chemotherapy leads to an absolute 5-year overall survival benefit of 5%. The single published meta-analysis comparing adjuvant and neo-adjuvant chemotherapy did not observe a significant difference on overall survival according to the two strategies.Perspectives: The dramatic benefit of tyrosine kinase inhibitors in advanced-stage nonsmall cell lung cancer harboring the EGFR mutation have led to question whether they might be interesting in the peri-operative setting for early stages. So far, few data are published, but seem very interesting regarding their interest as neo-adjuvant regimen in order to increase resecability, and in adjuvant settings to increase disease-free survival, in selected patients. ConclusionRegarding the published evidence, chemotherapy timing does not seem to impact overall survival. Role of tyrosine kinase inhibitors in peri-operative setting, even very interesting, has to be clearly defined.

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P < 0.01). For patients with EGFR-mutated NSCLC, the efficacy of TKI treatment was not statistically better than that of chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P < 0.01). The local response rate (RR)and disease control rate (DCR)with regimen including pemetrexed were greater than those with regimen including paclitaxel (P < 0.05). Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

3111 Benefit of tyrosine kinase inhibitors among the older compared with younger patients in non-small cell lung cancer

3111 Benefit of tyrosine kinase inhibitors among the older compared with younger patients in non-small cell lung cancer

Incidence of Carcinogenic Pathways in non-squamous non-small cell lung cancer (NSq-NSCLC) in a community cancer center: Actionable driven mutations and their interactions with other genomic alterations.

e12562 Background: Since the first report by Mok T. et al. in 2008 showing clinical benefit of tyrosine kinase inhibitor for patients (pts) whose tumors harbor EGFR mutation, personalized medicine ...

Is there a benefit of TKIs among the elderly compared with younger patients in non-small cell lung cancer? a meta-analysis.

e20515 Background: Tyrosine kinase inhibitors (TKIs) have a much better benefit to risk balance among the elderly compared with younger patients and to chemotherapy. To our knowledge, there is no m...