Kinase-positive Non-small Cell Lung Research Articles

Abstract 7504: Longitudinal multi-omics characterization of circulating tumor cells from ALK positive NSCLC patients

Abstract Introduction: Anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+NSCLC) represents a distinct subtype of NSCLC characterized by oncogenic ALK gene mutations leading to ALK overexpression and activation in tumor cells. ALK+ NSCLC will frequently develop mutations during treatment, leading to nonresponse and eventually cancer relapse. Therefore, there is a critical need for sensitive technologies to monitor ALK+ NSCLC disease status in patients over time. To facilitate longitudinal monitoring, there has been a rapid evolution in diagnostic technologies leveraging circulating tumor cells (CTCs) as a liquid biopsy tool. CTCs can be collected non-invasively at various intervals throughout patient treatment. Moreover, they shed from solid tumors and disseminate into the bloodstream, which makes isolating CTCs a valuable source of genomic, transcriptomic, and proteomic insights pertaining to the primary tumor. In this study, we present a comprehensive workflow for conducting multi-omic analysis on CTCs derived from ALK+ NSCLC patients. Methods: Blood samples were collected from a cohort of ALK+ NSCLC patients, and CTCs were isolated using a high throughput, label free microfluidic device, Labyrinth. Enriched CTCs were immunofluorescently stained for cytokeratin, CD45, DAPI, epithelial cell adhesion molecule (EpCAM), and vimentin markers. Heterogeneous CTC populations with hybrid epithelial/mesenchymal (EM) phenotypes are reported. Fluorescence in situ hybridization (FISH) was performed on enriched CTC samples. DNA was extracted and sequenced using a 523 gene targeted sequencing panel. Single cell RNA-seq technology was performed in parallel on CTC samples to investigate the gene expression throughout treatment. Results: The median concentration of CTCs in the ALK+ NSCLC cohort (n=33) is 137 CTCs per ml of blood, and 64% of CTCs are in an EM hybrid state. In ALK+ NSCLC patients (n=3) with an average of 4.6 visits per sample, we observed a trend of decreasing CTC concentration for patients with partial response to the treatment. The presence of ALK fusion in ALK+ NSCLC patient’s CTC is confirmed by FISH. Oncogenic mutations (JAK1, SPEN, ERBB4, NTRK3) are observed in bulk CTC samples from two NSCLC patients. Single cell RNA sequencing was performed on three ALK+ NSCLC patients; 58, 199, and 700 potential CTCs were detected with positive cytokeratin expression and no white blood cell marker expression. Conclusions: This study examined the feasibility of using CTCs for studying and monitoring the clinical status of the ALK+ NSCLC patients as well as the genomic and transcriptomic signatures within their tumors. More patients will need to be processed in order to validate our workflow and reinforce our conclusions. Citation Format: Yuru Chen, Shamileh Fouladdel, Harrison Ball, Zhaoping Qin, Albert Liu, Xu Cheng, Liwei Bao, Habib Serhan, Bryce Vandenburg, Varun Kathawate, Larua Goo, Peter Ulintz, Nathan Merrill, Aaron Udager, Angel Qin, Sofia D. Merajver, Sunitha Nagrath. Longitudinal multi-omics characterization of circulating tumor cells from ALK positive NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7504.

EE75 Cost Analysis of Managing Brain Metastases in Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer in Greece

EE75 Cost Analysis of Managing Brain Metastases in Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer in Greece

Salvage Surgery After First-Line Alectinib for Locally-Advanced/Metastatic ALK-Rearranged NSCLC: Pathological Response and Perioperative Results

BackgroundThe role of salvage surgery after tyrosine kinase inhibitors in advanced oncogene-addicted non-small cell lung cancer is largely unexplored. PatientsWe aimed to describe the pathological features and surgical early-outcomes of Anaplastic Lymphome Kinase anaplastic lymphome kinase positive non-small cell lung cancer patients undergoing surgery after first-line alectinib treatment. We retrospectively collected and analyzed multicentric data of 10 patients treated with alectinib for advanced-stage anaplastic lymphome kinase positive lung adenocarcinoma who underwent anatomical surgical resection from January 2020 to Decemeber 2021. All patients were treatment naive and received alectinib (600 mg twice daily). Surgery was always proposed after multidisciplinary discussion. The primary endpoints were pathological response and surgical feasibility (technical intraoperative complications, postoperative outcomes). ResultsAlectinib was received for a mean of 212 days before surgery (42-415 days) and was generally interrupted about one week before surgery (range: 0-32 days) with no patient experienced grade 4 toxicity. All patients received an R0 resection with surgery consisting of lobectomy in 8 cases with bilobectomy and (left) pneumonectomy in 1 case each. Intra-operative difficulties were described in 7 cases (70%), mostly due to perivascular fibrosis or thickening of mediastinal lymph nodal tissues. Major and minor complications occurred in 0 and 3 cases (30%), respectively. A pathological complete response and major pathological response (defined as 0% and < 10% viable tumor cells, respectively) were observed in 50% and 90% of cases, respectively. Despite short follow-up, only one tumor recurrence was observed (in the only patient who did not resume alectinib after surgery). InterpretationDespite some technical intraoperative difficulties, salvage surgery was safe and feasible after Alectinib for advanced lung adenocarcinoma.

Molecular determinants of clinical outcomes for anaplastic lymphoma kinase–positive non-small cell lung cancer in Chinese patients: A retrospective study

Gene complexity affects the clinical outcomes of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we reviewed the medical records of patients with NSCLC between September 2015 and December 2020 in a single institution. We examined the clinical and genomic predictors of these outcomes using multivariate Cox proportional hazards analysis. Overall, 105 patients with ALK-rearranged NSCLC were included. Echinoderm microtubule-associated protein-like 4 (EML4) was the predominant fusion partner (96.2%). Five patients (4.8%) had non-EML4 fusion partners; three had novel partners. EML4::ALK variant 3 (36.5%) was predominant. One patient had the following three subtypes: E13::A20, E6ins33::A20, and E20::A20. Median progression-free survival (PFS), but not overall survival (OS), was significantly different between patients with variants 3 and 1. TP53 was the most common concomitant mutation (21.4%). The presence of TP53 mutations was associated with shorter PFS among patients who received ALK-TKI. Patients with concomitant oncogene mutations presented significantly shorter OS and PFS than those with only ALK rearrangement. In a multivariate Cox regression model, concomitant oncogene mutations and variant 3 carrier status were prognostic factors for PFS, whereas baseline brain metastasis was a prognostic factor for OS.

139 - Using qualitative research to determine the impact of brain metastases (BM) on the advanced anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+ NSCLC) patient experience

139 - Using qualitative research to determine the impact of brain metastases (BM) on the advanced anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+ NSCLC) patient experience

Brigatinib versus other second-generation ALK inhibitors as initial treatment of anaplastic lymphoma kinase positive non-small cell lung cancer with deep phenotyping: study protocol of the ABP trial

BackgroundAvailability of potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) has pushed the median survival of ALK+ non-smallcell lung cancer (NSCLC) patients to over five years. In particular, second-generation ALK TKI have demonstrated superiority compared to the first-generation compound crizotinib and are meanwhile standard first-line treatment. However, clinical courses of individual patients vary widely, with secondary development of drug resistance and intracranial progression remaining important problems. While these limitations highlight the need for better disease monitoring and additional therapeutic tools, molecular tumor features are increasingly recognized as crucial determinants of clinical outcome. This trial aims to optimize management of ALK+ NSCLC by analyzing the efficacy of second-generation ALK inhibitors in conjunction with deep longitudinal phenotyping across two treatment lines.Methods/designIn this exploratory prospective phase II clinical trial, newly diagnosed ALK+ NSCLC patients will be randomized into two treatment arms, stratified by presence of brain metastases and ECOG performance status: brigatinib (experimental arm) vs. any other approved second-generation ALK TKI. Tumor tissue and blood samples will be collected for biomarker analysis at the beginning and throughout the study period to investigate baseline molecular tumor properties and analyze the development of acquired drug resistance. In addition, participating investigators and patients will have the possibility of fast-track molecular tumor and ctDNA profiling at the time of disease progression using state-of-the-art next-generation sequencing (NGS), in order to support decisions regarding next-line therapy.DiscussionBesides supporting therapeutic decisions for enrolled patients, the ABP trial primarily aims to deepen the understanding of the underlying biology and facilitate development of a framework for individualized management of ALK+ NSCLC according to molecular features. Patients with low molecular risk and the perspective of a “chronic disease” will be distinguished from “high-risk” cases, molecular properties of which will be utilized to elaborate improved methods of non-invasive monitoring and novel preclinical models in order to advance therapeutic strategies.Trial registrationClinicaltrials.gov, NCT04318938. Registered March 182,020, https://www.clinicaltrials.gov/ct2/show/NCT04318938Eudra-CT, 2019–001828-36. Registered September 302,019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-001828-36

P84.11 Real-World Brigatinib Dosing Patterns in Patients with Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer in the United States

Standard dosing of brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor for treating ALK+ non-small cell lung cancer is 90 mg once daily for 7 days then escalated to 180 mg on Day 8 as tolerated. Among patients receiving this standard dose, 29% in the post-crizotinib ALTA trial and 38% in the tyrosine kinase inhibitor (TKI)-naïve ALTA-1L trial required a dose reduction. Asymptomatic laboratory abnormalities including creatine phosphokinase, amylase or lipase elevations were common causes of dose reductions in these studies. Outside of trial protocol mandated dosing, real-world dosing patterns of brigatinib have not been previously described. Adult (≥18 years) patients with ≥1 claim for brigatinib were identified between 01 April 2017 and 31 August 2019 from the IQVIA longitudinal pharmacy claims database and followed until the earliest of: dose reduction, treatment discontinuation, or end of follow-up. Average daily dose (ADD) was calculated as the product of pill strength and quantity of pills dispensed divided by the day supply. Dose reduction was defined as ≥30 days of supply with ADD < 180 mg/day after reaching 180 mg/day, or < maximum (max) dose in patients who did not reach 180 mg/day. Time to dose reduction from 180 mg/day or max dose and probability of continued therapy at ≥180 mg/day or max dose were assessed via Kaplan-Meier analysis. Adherence was defined using medication possession ratio (MPR) and dose compliance score (DCS) was calculated as total dosage received divided by total dosage expected. A total of 240 brigatinib patients were identified. Median age was 58 years, 57.9% were female and 85.4% had ≥1 prior TKI. Mean (standard deviation) follow-up time was 10.7 (7.6) months. A dose of 180 mg/day was achieved in 202 (84.2%) patients, of which 87.1% were treated after 1+ prior lines. Dose reduction occurred in 15.8% of patients who reached 180 mg/day, and the probability of continued therapy at ≥180 mg/day in patients still on therapy at 3 and 6 months after dose escalation was 89.5% and 86.0%, respectively. Of the patients with dose reduction, 43.8% reduced to 120 mg/day. A total of 38 (15.8%) patients did not reach 180 mg/day. Dose reduction occurred in 13.2% of these patients, and the probability of continued therapy at the max dose at 3 and 6 months after max dose was reached was 94.1% and 89.8%, respectively. Among the patients with dose reduction, 40.0% reduced to 90 mg/day. Adherence and dose compliance were high overall with 93.3% of patients having MPR > 80% and median DCS of 1.0 (0.3-2.2). Real-world data suggest that standard dose escalation (90 to 180 mg) occurs in most brigatinib patients (>84%) and that dose reduction rates may be lower outside the protocol mandated confines of clinical trials. Adherence and dose compliance were high. Analysis with longer follow-up time may be warranted to further evaluate these findings.

RET Rearrangement as a Predictor of Unresponsiveness to Immunotherapy in Non-Small Cell Lung Cancer: Report of Two Cases with Review of the Literature.

Patients with epidermal growth factor receptor and anaplastic lymphoma kinase positive non-small cell lung cancer (NSCLC) generally respond poorly to treatment with immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) given with or without anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) drugs. However, the efficacy of immunotherapy in patients with oncogene-addicted NSCLC harboring minor drivers, such as fusions in the rearranged during transfection (RET) gene, is still unclear. Here we describe two patients with RET-positive advanced NSCLC with PD-L1 expression ≥ 50% who developed progressive disease during first-line treatment with the anti-PD-1 agent pembrolizumab. In particular, while patient 2 was immediately switched to treatment with a selective RET inhibitor within the setting of a clinical trial, patient 1 responded to cytotoxic chemotherapy delivered at the time of progression while on pembrolizumab. These cases of NSCLC are discussed in the context of current literature, which seems to support our observation that patients with RET-positive NSCLC are unlikely to benefit from immunotherapy. Therefore, we suggest that for RET-positive patients with PD-L1 ≥ 50%, consideration should be given to upfront treatment approaches other than single-agent immunotherapy, namely selective RET inhibitors (if available) or regimens including cytotoxic chemotherapy.

Effect of the patient information brochure in communicating the risks associated with crizotinib treatment to patients with non-small cell lung cancer (NSCLC) in Europe.

Crizotinib (XALKORI®) is indicated for anaplastic lymphoma kinase‐positive and ROS1‐positive advanced non‐small cell lung cancer. This study evaluated the distribution of the crizotinib patient information brochure (PIB) in Europe and patient knowledge of the key messages in the PIB. A cross‐sectional survey was conducted in 10 European countries among patients who received crizotinib to ascertain whether each patient received and read the PIB, and his/her knowledge of its key messages on hepatotoxicity, interstitial lung disease/pneumonitis, QTc prolongation, bradycardia, and vision disorders. Of the 341 patients contacted, 40 responded (11.7%), and 39 patients were eligible. A total of 77% of respondents acknowledged receiving the PIB, of which, 93% reported reading it. Knowledge of the individual side effects ranged from 36% to 85%, and precautions for use ranged from 56% to 67%. Understanding the reasons for calling a physician ranged from 54% to 85%. Knowledge of each of the 6 key side effects was greater among readers of the PIB compared to non‐readers or respondents who did not recall receiving the PIB. Approximately three‐quarters of survey respondents recalled receiving the crizotinib PIB and respondents who read the PIB were more knowledgeable of the key side effects of crizotinib than those who did not read or receive. Caution should be taken in generalizing these results because of the potential for selection bias and small sample size. These survey results suggest that the crizotinib PIB may be an effective risk communication tool for crizotinib‐treated patients in Europe.

ASCEND-8 pharmacokinetic, safety, and efficacy data for ceritinib 450 mg with food in patients with anaplastic lymphoma kinase–positive non-small cell lung Cancer: A clinical perspective

Anaplastic lymphoma kinase–positive (ALK+) non-small cell lung cancer (NSCLC) is diagnosed in up to 126,000 patients worldwide annually. Ceritinib is a next-generation ALK-targeted tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic ALK+ NSCLC. In December 2017, the US Food and Drug Administration–approved dose of ceritinib was changed from 750 mg/day under fasting conditions to 450 mg/day taken with food for the treatment of patients with ALK+ NSCLC. This change was implemented on the basis of data from studies designed to investigate ways to reduce the frequency of gastrointestinal adverse events noted in patients enrolled in several ASCEND clinical trials that evaluated a ceritinib 750-mg fasted dose as either first- or second/third-line treatment. This review highlights and discusses published findings from the ASCEND-8 food-effect trial and includes commentary from physicians regarding their own clinical cases of patients who were enrolled in the trial and treated with either the 750-mg fasted or 450-mg fed dose of ceritinib. The review also discusses the implications of using the recently approved ceritinib 450-mg dose in the clinical setting.

1500TiP - eXalt3: Phase III randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase positive non-small cell lung cancer patients

1500TiP - eXalt3: Phase III randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase positive non-small cell lung cancer patients

Crizotinib in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer versus chemotherapy as a first-line treatment

BackgroundTo compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86–571-87,236,876 predictive clinical factors of the efficacy of crizotinib.MethodsThe 73 patients with ALK-positive advanced NSCLC were divided into three groups based on the first-line treatment: first-line crizotinib group (1-CRZ group, n = 32); first-line platinum-based pemetrexed treatment group (1-PP group, n = 28), and first-line chemotherapy platinum-based non-pemetrexed group (N1-PP, n = 12). Sixty eight of the 73 patients received crizotinib treatment and followed up in our hospital. Differences in the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared in the different groups. The clinical factors were evaluated to predict the efficacy of crizotinib by the Kaplan–Meier survival analysis and Cox proportional hazards model.ResultsThe PFS, ORR, DCR were 16.1 months, 78.1% (25/32) and 100% (32/32) in the 1-CRZ group; were 6.0 months, 17.9% (5/28) and 57.2% (16/28) in the 1-PP group; and were 2.9 months, 15.4% (2/13) and 46.2% (6/13) in the N1-PP group. The PFS of the 1-CRZ group was significantly longer than that of the 1-PP group (P < 0.001) and the N1-PP group (P < 0.001). The ORR and DCR of the 1-CRZ group was significantly greater than that of the 1-PP group and the N1-PP group (all the P < 0.001). Higher Eastern Cooperative Oncology Group (ECOG) performance status score (> = 2) (HR 2.345, 95% CI 1.137–4.834, P = 0.021) and patients received crizotinib after N1-PP chemotherapy (HR 2.345, 95% CI 1.137–4.834, P = 0.021) were two factors associated with shorter PFS after crizotinib treatment.ConclusionsIn patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR. Higher ECOG score (> = 2) and patients received crizotinib after N1-PP chemotherapy predict poor efficacy of crizotinib.

Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada

Background: To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective.Methods: A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed.Results: Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings.Conclusion: Based on the willingness-to-pay threshold for end-of-life cancer drugs, ceritinib may be considered as a cost-effective option compared with other alternatives in patients who have progressed or are intolerant to crizotinib in Canada.

Cost-Effectiveness of Ceritinib Versus Current Therapies for Chemotherapy-Experienced Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients in Mexico

Cost-Effectiveness of Ceritinib Versus Current Therapies for Chemotherapy-Experienced Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients in Mexico

Abstract 781: The potent ALK inhibitor AP26113 can overcome mechanisms of resistance to first- and second-generation ALK TKIs in preclinical models

Abstract Background: Disease progression in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) patients (pts) treated with the first-generation tyrosine kinase inhibitor (TKI) crizotinib, or the second-generation inhibitors ceritinib and alectinib, is often associated with secondary resistance mutations in ALK (such as G1202R, linked with resistance to all 3 TKIs in pts), or relapse in the brain. AP26113 is a highly potent ALK inhibitor with promising anti-tumor activity in pts with crizotinib-resistant disease. Here we broadly evaluate AP26113's ability to overcome mechanisms of resistance to first- and second-generation ALK inhibitors, in preclinical models (including brain cancer models), and describe a novel methodology to compare in vitro potency, clinical pharmacokinetic parameters, and clinical efficacy. Methods: Ba/F3 cells were engineered to express native EML4-ALK or 17 mutants resistant to crizotinib, ceritinib, and/or alectinib in clinical or preclinical studies. IC50s for all TKIs were compared to “clinically effective” plasma concentrations (Ceff) of each inhibitor, which were derived using average steady-state levels in pts, and corrected for the functional effects of protein binding in vitro. In vivo studies were performed in mice, in which Ba/F3 cells with mutant or native EML4-ALK were injected subcutaneously, or a NSCLC line with EML4-ALK (H2228) was injected into the brain. Results: The Ceff of crizotinib was only ∼2-fold above the IC50 for native ALK, suggesting that crizotinib may be susceptible to mutants that inhibit binding by only a few-fold. Indeed, 8/10 mutants previously associated with clinical resistance to crizotinib were found to have IC50s that exceed the Ceff. Similar analyses revealed mutants with IC50s that exceeded the Ceff for ceritinib (e.g. L1198F) and alectinib (e.g. I1171N), with G1202R being the most recalcitrant mutant overall. In contrast, the Ceff of AP26113 was &amp;gt;20-fold above the IC50 for native ALK, and exceeded the IC50 for all 17 mutants, including G2102R. In vivo, among all 4 TKIs tested (at doses effective against native ALK), only AP26113 demonstrated significant efficacy against G1202R-mutant ALK (88% tumor growth inhibition). Finally, compared to crizotinib, AP26113 markedly enhanced survival of mice bearing brain tumors. Conclusion: AP26113 inhibits all 17 clinically and preclinically observed crizotinib-, ceritinib-, and/or alectinib-resistant ALK mutants tested in vitro, has potent effects on the recalcitrant G1202R mutant in vivo and has activity in an orthotopic brain model. These results suggest AP26113 may effectively address a broad range of resistance mechanisms identified for other ALK TKIs. AP26113 is currently in a global phase 2 registration trial in patients with locally advanced or metastatic ALK+ NSCLC who were previously treated with crizotinib (NCT02094573). Citation Format: Sen Zhang, Sara Nadworny, Scott D. Wardwell, Lindsey Eichinger, Biplab Das, Emily Y. Ye, J. Graeme Hodgson, Victor M. Rivera. The potent ALK inhibitor AP26113 can overcome mechanisms of resistance to first- and second-generation ALK TKIs in preclinical models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 781. doi:10.1158/1538-7445.AM2015-781

Comparative efficacy of ceritinib and crizotinib in previously treated crizotinib-naïve anaplastic lymphoma kinase-positive (ALK+) advanced or metastatic non-small cell lung cancer (NSCLC): An adjusted indirect comparison.

8058 Background: Ceritinib (CER) has been studied in previously treated, crizotinib (CRZ)-naive patients (pts) in two clinical trials (ASCEND-1: NCT01283516; ASCEND-3: NCT01685138). No randomized c...