Posts in Conference Paper
Outcomes Based On Brain Metastases Characteristics And Treatment Modality For Patients With EGFR-Mutated And ALK-Rearranged Non-Small Cell Lung Cancer (NSCLC)
Outcomes Based On Brain Metastases Characteristics And Treatment Modality For Patients With EGFR-Mutated And ALK-Rearranged Non-Small Cell Lung Cancer (NSCLC)

Purpose/objective(s): Lung cancer patients with driver mutations and brain metastases can be managed with various modalities given intracranial penetrance of available tyrosine kinase inhibitors (TKIs). We sought to determine these patient’s outcomes based on brain metastases characteristics and the upfront treatment modalities utilized, including stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT). Conclusion: For patients with EGFR-mutated or ALK-rearranged NSCLC and brain metastases, there was no difference in IC-PFS based on number or volume of brain metastases. Those treated with TKI alone experienced similar IC-PFS and risk of neurologic death as those also treated with radiotherapy. Further studies are needed to evaluate optimal treatment strategies for these patients, particularly for those with larger or symptomatic brain metastases when radiation is typically recommended. READ ARTICLE

International Journal of Radiation Oncology DOI:10.1016/j.ijrobp.2020.07.2048

Authors: S.W. Dutta, M.L. Mack, K.A. Ward, E. Aliotta, R. Hall, R.D. Gentzler, J.P. Sheehan

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Conference PaperKirk Smithradiation, targeted therapy, brain metastases, non-small cell lung cancer (NSCLC), EGFR inhibitors, ALK inhibitors
Abstract 4900: An ALK fusion gene regulates different signaling pathways in mortal versus immortalized normal human cells for cellular senescence and transformation
Abstract 4900: An ALK fusion gene regulates different signaling pathways in mortal versus immortalized normal human cells for cellular senescence and transformation

Accumulating results of clinical trials lead targeted therapies to be the first choice for unresectable or recurrent lung cancer with driver mutations. Echinoderm Microtubule Associated Protein Like 4 (EML4) - Anaplastic lymphoma kinase (ALK) fusion is known as such a driver mutation. It presents in 3-6% of non-small cell lung carcinoma (NSCLC). EML4-ALK fusion protein generate the constitutive ALK kinase activity in NSCLC. The basic understanding of EML4-ALK remains insufficient due to the lack of functional studies using normal human cells. We investigated the role of EML4-ALK in mortal and immortalized normal human cells. The expression of EML4-ALK in normal, mortal human fibroblasts caused accumulated DNA damage, telomere shortening and the early induction of cellular senescence with senescence-associated beta-galactosidase activity and upregulation of p16INK4A and p21WAF1. In contrast, when EML4-ALK was expressed in telomerase reverse transcriptase (hTERT)-immortalized normal huma..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-4900

Authors: Masaru Matsumoto, Akihiko Miyanaga, Jessica Beck, Izumi Horikawa, Mohammed Khan, Delphine Lissa, Masahiro Seike, Akihiko Gemma, Hiroyuki Mano and Curtis Harris

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Conference PaperKirk SmithEML4-ALK, non-small cell lung cancer, NSCLC
Immune exhaustion of tumor microenvironment mediates crizotinib resistance in ALK rearranged advanced non small cell lung cancer
Immune exhaustion of tumor microenvironment mediates crizotinib resistance in ALK rearranged advanced non small cell lung cancer

Previous study showed the correlation between immune tumor microenvironment and the efficacy of checkpoint inhibitor in non-small cell lung cancer (NSCLC). This study evaluated whether biomarkers for immune tumor microenvironment including programmed death ligand 1 (PD-L1), cluster of differentiation 8 (CD8), Granzyme B (GZMB) and T cell receptor (TCR) could predict the treatment response to the first-line crizotinib of patients with ALK-rearranged non-small cell lung cancer (NSCLC).We retrospectively evaluated patients with advanced NSCLC who received crizotinib at Hunan Cancer Hospital between January 2016 and December 2018.his study revealed immune exhaustion for tumor microenvironment as a poor predictive marker in first-line crizotinib-treated ALK-rearranged non-small cell lung cancer. The findings indicate the reshaping of an inflamed immune phenotype characterized by PD-L1, CD8, GZMB, and TCR expression and suggest potential therapeutic sensitivity to PD-1 blockade. READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-4479

Authors: Yongchang Zhang

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Conference PaperKirk Smithcrizotinib, ALK, microenvironment, advanced non small cell lung cancer
Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay
Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay

Detection of genomic rearrangements like ALK fusions are of great interest in non-small cell lung cancer (NSCLC) as those alterations can be targeted by an increasing number of drugs. To overcome tissue limitations, detection of these alterations from liquid biopsies is an unmet need, despite the development of novel NGS-based tests. To allow the detection of ALK rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel RT-PCR based assay and compared the results to tissue-based testing using immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH).The prototype cobas ALK/RET/ROS1 Fusion Panel assay was able to detect ALK fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression. Limited sensitivity could be explained by biological factors influencing nucleic acid shedding by tumours, as well as the presence of fusions not covered by the assay. However, the assay demonstrated high specificity. T..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-5299

Authors: Simon Heeke, Marius Ilié, Maryline Allegra, Audrey Vallée, Carole Salacroup, Virginie Tanga, Véronique Hofman, Jaya Rajamani, Michael Lee, Ellen Ordinario, Marc G. Denis and Paul Hofman

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Conference PaperKirk SmithALK, non-small cell lung cancer, NSCLC, cobas, RET, ROS1
TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors
TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors

Anaplastic lymphoma kinase (ALK) gene rearrangements occur in up to 7% of patients with non-small cell lung cancer (NSCLC) with the majority as EML4-ALK fusions. Crizotinib (first generation ALK inhibitor) was the first approved ALK inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer. However, development of resistance to crizotinib caused by secondary kinase domain mutations, bypass signaling, or morphology changes occurs. Second generation ALK inhibitors alectinib, ceritinib, and brigatinib were able to overcome the majority of ALK resistant mutations (L1196M, G1269A and F1174L) acquired with crizotinib. The solvent front mutation (SFM) G1202R is a common resistant mutation to crizotinib and the second generation ALK inhibitors. Lorlatinib, a third generation ALK inhibitor, can overcome G1202R resistance with moderate IC50 values of 40 - 60 nM in cell-based assays. Although, compound mutations such as ones with both gatekeeper and solvent front mutations..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-5226

Authors: J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee and Brion Murray

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Conference PaperKirk SmithALK, EML4-ALK fusions, NSCLC, ALK positive, TPX-0131
Longitudinal analysis of cell-free DNA for therapy monitoring of ALK-positive non-small cell lung cancer
Longitudinal analysis of cell-free DNA for therapy monitoring of ALK-positive non-small cell lung cancer

Non-small cell lung cancer (NSCLC) patients with ALK rearrangements are routinely treated with tyrosine kinase inhibitors (TKIs), leading to improved survival. However, clinical courses vary widely and the disease remains incurable. Therefore, early detection and molecular characterization of treatment failure is important for therapy guidance. To identify indicators of therapy response and resistance, we performed genotyping of circulating cell-free DNA (cfDNA), including panel-based deep sequencing (>4,200x coverage) and shallow whole-genome sequencing (sWGS; 0.5x coverage) from serial plasma samples (n=282) of 73 patients with ALK rearrangements. Variable mutation levels were marked in all patients and correlated with clinical features. At progression, individual dynamics of resistance mutations were seen: while some mutations became undetectable upon therapy switch, variant fractions of other alterations further increased. We also found mutated TP53 at the time of progression in pa..... READ ARTICLE

Clinical Cancer Research DOI:10.1158/1557-3265.LiqBiop20-A21

Authors: Steffen Dietz, Petros Christopoulos, Lisa Gu, Volker Endris, Zhao Yuan, Simon J. Ogrodnik, Tomasz Zemojtel, Marc A. Schneider, Anna-Lena Volckmar, Michael Meister, Thomas Muley, Martin Reck, Matthias Schlesner, Michael Thomas, Albrecht Stenzinger, Holger Sültmann.

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Conference PaperKirk SmithALK, sequencing, resistance mutations
SPACEWALK: Plasma NGS for remote evaluation of ALK drug resistance in advanced NSCLC
SPACEWALK: Plasma NGS for remote evaluation of ALK drug resistance in advanced NSCLC

Introduction: Precision therapy for cancer drug resistance requires detection of resistance mutations and treatment with appropriate targeted therapies. This paradigm is well established in EGFR-mutant NSCLC, yet our understanding of drug resistance in ALK-positive NSCLC is limited. Next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA) now permits noninvasive interrogation of drug resistance. To facilitate improved understanding of ALK drug resistance and the effectiveness of treatment strategies, we launched this remote participation study. Conclusions: Plasma NGS permits the detection of targetable resistance mechanisms in patients with ALK-positive NSCLC and drug resistance. Sensitivity of different plasma NGS assays for ALK fusions varies. This assay may help guide oncologists across the country to select best treatment options after resistance. Such remote-participation studies may offer a new mechanism for characterizing resistance to emerging targeted therapies in rare cancer populations. READ ARTICLE

Clinical Cancer Research DOI:10.1158/1557-3265.LiqBiop20-A28

Authors: Marissa N. Lawrence, Rubii M. Tamen, Alicia Sable-Hunt, Seyed Ali Hosseini, George R. Simon, Jonathan W. Riess, Geoffrey R. Oxnard.

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Conference PaperKirk SmithNGS, resistance mechanisms, ALK, drug resistance
Abstract A125: Predication of lorlatinib resistance mechanisms and therapeutic strategies to overcome the resistance in ALK rearranged non-small cell lung cancer
Abstract A125: Predication of lorlatinib resistance mechanisms and therapeutic strategies to overcome the resistance in ALK rearranged non-small cell lung cancer

Introduction: ALK fusion gene is found in 3-5% of NSCLC patients. As the resultant ALK fusion protein constitutively activates ALK tyrosine kinase that causes tumorigenesis, ALK tyrosine kinase inhibitors have been developed for the treatment of ALK rearranged cancer and currently five ALK-TKIs have been clinically applied. Now, alectinib is widely used in first-line therapy. However, most of the patients experience the emergence of alectinib resistance due to the secondary mutation in ALK kinase domain such as I1171N or G1202R. Lorlatinib, third generation ALK-TKI, has shown to be able to overcome any of the earlier generation ALK-TKI resistant single point mutants including G1202R and I1171N. Conclusion: Our results imply that the clinical sequences after lorlatinib resistance using biopsy or liquid-biopsy might provide important information to choose the effective sequential ALK-TKI therapy. Further studies are still needed to uncover the unidentified lorlatinib resistance mechanisms. READ ARTICLE

Molecular Targets and Cancer Therapeutics DOI:10.1158/1535-7163.TARG-19-A125

Authors: Koutaroh Okada, Mitsugu Araki, Tomoko Oh-hara, Makoto Nishio, Yasushi Okuno, Naoya Fujita and Ryohei Katayama

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Conference PaperKirk SmithLorlatinib, resistance mechanisms, therapeutic strategies, ALK rearranged non-small cell lung cancer
P2.14-18 Upregulation of AURKA Leads to Acquired Resistance in EML4-ALK NSCLC Cell Line
P2.14-18 Upregulation of AURKA Leads to Acquired Resistance in EML4-ALK NSCLC Cell Line

Background: Molecular targeted therapies in NSCLC often results in profound initial patient responses, these responses are short-term due to the development of acquired resistance. In an EML4-ALK NSCLC background, acquired resistance can be developed in two ways ALK dependent (ALK secondary mutations) and ALK independent (alternative oncogenic pathways). In our study, we have shown that increased expression of Aurora kinase A (AURKA) leads to acquired resistance upon treatment with ALK TKI crizotinib. Conclusion: Our results indicate a new mechanism to acquire resistance upon treatment with ALK TKI crizotinib. Inhibition of both ALK and AURKA activity might be beneficial for ALK TKI resistant tumors with increased AURKA gene expression/activity. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1803

Authors: G. Umapathy, R. Palmer, B. Hallberg

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Conference PaperKirk SmithEML4-ALK, AURKA, Resistance
P114-01 Are Pretreatment Inflammation-Based Prognostic Scores Useful in Predicting the Outcomes of Patients with ALK-Positive NSCLC?
P114-01 Are Pretreatment Inflammation-Based Prognostic Scores Useful in Predicting the Outcomes of Patients with ALK-Positive NSCLC?

To date, upfront treatment with ALK-tyrosine-kinase inhibitors (ALK-TKIs) has replaced chemotherapy in the first line setting for this subset of patients with excellent results, but reliable prognostic markers are lacking. An increased systemic inflammatory response has been shown to be associated with a poor prognosis, and some of the parameters used to characterize this response can easily be measured in clinical practice in several tumor types, but have not been analyzed extensively in ALK+ lung cancer in the era of crizotinib.We reviewed the medical records of all patients with previously treated advanced ALK-positive NSCLC who received crizotinib between January 2013 and March 2018 outside of a clinical trial. The study found that, in a cohort of patients with ALK positive NSCLC treated with crizotinib in routine practice, elevated pre-treatment SII was associated with shorter OS and PFS in univariate analysis and PNI was associated with shorter OS in multivariate analyses. Moreov..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1152

Authors: O.F. Olmez, A. Bilici, P. Gursoy, E. Çubukçu, O. Yildiz, A. Sakin, T. Korkmaz, I. Cil, B. Cakar, S. Menekse, T. Demir, O. Acikgoz, J. Hamdard

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Conference PaperKirk SmithInflammation-based prognostic scores, Non small cell lung cancer, Anaplastic lymphoma kinase
P103-15 Non-Invasive Detection of Secondary Resistance Mutations in ALK-Positive NSCLC Patients by Next-Generation Sequencing
P103-15 Non-Invasive Detection of Secondary Resistance Mutations in ALK-Positive NSCLC Patients by Next-Generation Sequencing

Remarkably different mutations can confer different sensitivities to different ALK inhibitors. However, 2nd and 3rd line treatment is often prescribe empirically without knowing the molecular mechanism underlying treatment failure.21 samples from ALK-positive NSCLC patients were collected at disease progression. Circulating Nucleic Acids were isolated from platelets, exosomes and plasma. Libraries were prepared using 20ng of template and Oncomine™ Pan-Cancer Cell-Free Assay. Samples were sequenced on an Ion GeneStudio S5 Plus System. Sequencing data was first analyzed using Torrent Suite software. Subsequently variant calling, annotation and filtering was performed on the Ion Reporter (v5.10) platform using the Oncomine TagSeq Pan-Cancer Liquid Biopsy w2.1 workflow. The results show that secondary ALK-TKI resistance mutations could be detected using liquid biopsies in a high proportion of patients. Non-invasive molecular profiling of samples collected at disease progression is feasible being useful for further treatment selection in ALK-positive NSCLC patients.
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Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.867

Authors: E. Sánchez Herrero, M. Barquin, V. Calvo De Juan, M. Auglyte, R. Garcia Campelo, J.M. Sánchez, M. Domine, B. Massuti, E. Jantus, C. Camps, N. Reguart, M. Provencio, A. Romero

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Conference PaperKirk SmithctDNA, liquid biopsy, ALK
P101-129 Preclinical Genetic Evaluation of Alternating ALK TKI Therapy Versus Continuous Dosing in ALK NSCLC to Inform the ALKternate Clinical Trial
P101-129 Preclinical Genetic Evaluation of Alternating ALK TKI Therapy Versus Continuous Dosing in ALK NSCLC to Inform the ALKternate Clinical Trial

In a many patients the underlying cause of drug resistance is unexplained. ALKternate is a clinical trial recruiting pre-treated patients, testing the hypothesis that with fixed alternating TKI therapy, the emergence of ALK resistant clones can be suppressed through applying variable selection pressure compared to continuous treatment with a TKI. This has been tested pre-clinically with a human cell line to complement the clinical trial in progress, ALKternate.In keeping with the hypothesis, the genetic profiles identified demonstrate the emergence of different clones over time and between treatment strategies. This supports further investigation into the novel strategy of alternating therapy as planned in the ALKternate trial.
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Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.844

Authors: M. Itchins, A. Hudson, S. Hayes, R. Harvie, G.H. Wei, M. Buckland, S. Clarke, V. Howell, N. Pavlakis

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Conference PaperKirk SmithNSCLC, ALK, genetic, ALKernate
P101-93 Metastases Sites as a Prognostic Factor in a Real-World Multicenter Cohort Study of Spanish ALK-Positive NSCLC Patients (p)
P101-93 Metastases Sites as a Prognostic Factor in a Real-World Multicenter Cohort Study of Spanish ALK-Positive NSCLC Patients (p)

To date, published real-world data on the prognostic factors of patients with ALK-positive advanced NSCLC in Spain are limited. We aim to evaluate the effect of number of metastases (M1) organs on overall survival (OS) in a multicenter cohort of Spanish ALK-positive NSCLC p diagnosed between 2008 and 2017. We included p with stage IV at diagnosis since 2011 to April 2018. OS was worse with increased metastatic sites involved at diagnosis in p with ALK positive NSCLC, being liver M1 associated with the highest risk of mortality. Brain metastases at diagnosis were not a prognostic factor for OS in our series. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.808

Authors: L. Angelats, R. Garcia Campelo, R. Bernabe, E. Arriola, P. Rocha, V. Calvo De Juan, E. Sais, A. Barba, N. Viñolas, M. Gil Moreno, L. Vilà, O. Juan, N. Vilariño, M. Cobo, M. Domine, S. Vazquez, J. Coves, R. Marse-Fabregat, A.M. Esteve Gomez, E. Carcereny

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Conference PaperKirk SmithMetastases sites, Prognostic factor, ALK-positive NSCLC
P101-24 Preclinical Proteomic Evaluation of Alternating ALK TKI Therapy Versus Continuous Dosing in ALK NSCLC to Inform the ALKternate Clinical Trial
P101-24 Preclinical Proteomic Evaluation of Alternating ALK TKI Therapy Versus Continuous Dosing in ALK NSCLC to Inform the ALKternate Clinical Trial

In many patients the underlying cause of drug resistance is unexplained. ALKternate is a clinical trial recruiting pre-treated patients, testing the hypothesis that with fixed alternating TKI therapy, the emergence of ALK resistant clones can be suppressed through applying variable selection pressure compared to continuous treatment with a TKI. This has been tested pre-clinically with a human cell line to complement the clinical trial in progress, ALKternate In this study, ALK TKI treatment was conducted on resistant ALK-rearranged cell lines (methods in Abstract #2074). Protein profiling was performed using the SWATH-MS 2.0 algorithm, conducted on the Sciex 6600 TripleTOF on cell pellets collected prior to treatment and at cycles (C) 5, 11 and 17 of both alternating lorlatinib with crizotinib (ALT) and continual lorlatinib (CONT) treatment arms.This study represents the first of proteomics used to identify resistance mechanisms to ALK TKIs. Data from this in vitro work will inform th..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.739

Authors: M. Itchins, A. Hudson, R. Harvie, T. Zaw, M. Mckay, S. Clarke, V. Howell, N. Pavlakis, S. Hayes

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Conference PaperKirk SmithNSCLC, ALK, proteomic, ALKternate
EP116-32 Percentage of ALK Rearrangement as a Response Predictor in Non-Small Cell Lung Cancer Treatment
EP116-32 Percentage of ALK Rearrangement as a Response Predictor in Non-Small Cell Lung Cancer Treatment

Our study aimed to correlate the percentage of ALK rearrangement found as a predictor of response in NSCLC ALK-positive treatment. Designed a retrospective study with NSCLC ALK rearrangement patients in a peripheral Hospital from the last six years. Collected demographic data, histology, disease stage, the percentage of ALK rearrangement detected by FISH, lines of treatment, the response rate (RR) evaluated by RECIST 1.1 criteria, the progression-free survival (PFS) and the overall survival (OS) in patients under ALK inhibitors. Results are presented as medians and range for non-normally distributed continuous variables and as number/total for categorical data. Statistical analysis was performed using U-Mann-Whitney test, considering a significance level of 5%. Besides our negative results with the the percentage of ALK rearrangement, we found in our sample an improvement in the RR, PFS and OS in patients that made in first line, ALK inhibitors rather than platinum-based chemotherapy, ..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2397

Authors: M. Oliveira, R. Natal, J. Costa, R. Gomes, A. Amaral, L. Ferreira

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Conference PaperKirk SmithNon-Small Cell Lung Cancer, ALK rearrangement, Response predictor
EP116-28 ALK Translocated Patients: Survival in an Unselected Population
EP116-28 ALK Translocated Patients: Survival in an Unselected Population

A cohort of 34 patients diagnosed of non-small cell lung cancer with ALK translocation were retrospectively analyzed in our center between 2008-2018. Baseline demographics characteristics were described. OS was calculated as the main objective.Patients were followed a median of 47 months (IQR 30-203). Median age was 59 years (IQR 36-83), being 47% male and 53% female. 44% were never smokers and 58% had any comorbidities. At diagnosis, 83% were symptomatic and the most frequent metastases were bone ones (32%). Complete baseline characteristics are shown in Table 1. Median OS was 32 months (IQR 15-78). 1-year, 2-year and 3- year survival was 75%, 69% 49.9% respectively. The ALK translocation and targeted treatments have led to a dramatic improvement in overall survival in clinical trials confirmed in our series. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2393

Authors: B. Núñez-García, R. Gómez-Bravo, J.C. Sánchez, B. Cantos, M. Méndez, A.M. Morito, M. Blanco, V. Calvo, M. Provencio

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Conference PaperKirk SmithNSCLC, ALK mutation, OS
EP114-07 Efficacy and Safety of ALK Inhibitors in ALK-Rearranged Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
EP114-07 Efficacy and Safety of ALK Inhibitors in ALK-Rearranged Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

We conducted a systematic review and meta-analysis to assess the efficacy and safety of ALK inhibitors compared to chemotherapy (ALK vs. chemo) and 2nd generation ALK inhibitors compared to 1st generation ALK inhibitors (ALK 2G vs. ALK 1G).The electronic databases PubMed and EMBASE, were searched for relevant randomized trials. Pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS), and pooled risk ratios for objective response rates (ORR) and grade 3 or higher toxicity were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. To account for between-studies heterogeneity, random-effect models were used. Subgroup analyses compared PFS by gender, smoking status, brain metastases, race and age.This meta-analysis is the first, to our knowledge, to report an OS improvement with the use of ALK vs. chemo. A trend toward a better OS was also seen with ALK 2G vs. ALK 1G and this is likely because of crossover effects and limited OS f..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2292

Authors: D. Breadner, S. Shanmuganatjan, G. Boldt, P. Blanchette, J. Raphael

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Conference PaperKirk SmithALK, Targeted therapy, advanced NSCLC
EP114-02 Comparative Efficacy of First-Line Ceritinib at a Dose of 450mg with Food and Alectinib in Advanced ALK+ NSCLC
EP114-02 Comparative Efficacy of First-Line Ceritinib at a Dose of 450mg with Food and Alectinib in Advanced ALK+ NSCLC

Ceritinib and alectinib were both second generation of ALK inhibitors that approved as first-treatment for ALK+ NSCLC. Ceritinib is initially approved at the recommended dose of 750 mg/day fasted (ceritinib 750-mg fasted). Ceritinib at a dose of 450 mg with food (ceritinib 450-mg fed) compared to ceritinib 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity in the Ascend 8 trial. Although a previous cross-study indirect study compared the efficacy of ceritinib 750-mg fasted with alectinib, the efficacy of ceritinib 450-mg fed compared with alectinib is unknown. Progression-free survival of ceritinib 450-mg fed was indirectly compared with that of alectinib using a Bucher anchor-based indirect comparison approach using ceritinib 750-mg fasted as the common anchor. The comparative efficacy of alectinib vs ceritinib 750-mg fasted was obtained from matching-adjusted indirect comparison(MAIC) and the comparative efficacy of ceritinib 450-mg fed vs ceritinib 750-mg fa..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2287

Authors: F. Liang, D. Shen

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Conference PaperKirk SmithALK, Ceritinib, alectinib]
P116-46 Genetic Testing Patterns, Treatment Characteristics, and Overall Survival in ALK-Positive Metastatic NSCLC Patients Treated with Ceritinib
P116-46 Genetic Testing Patterns, Treatment Characteristics, and Overall Survival in ALK-Positive Metastatic NSCLC Patients Treated with Ceritinib

This study therefore sought to assess ALK testing patterns, treatment characteristics, and overall survival (OS) in patients with mNSCLC treated with ceritinib in routine practice.87 patients were selected (median age: 53 years). Nearly 56% of patients had been tested for ALK mutation before initiating the first-line therapy (1L); 72% were tested before 2L and 77% before 3L. The most common regimens were cisplatin/pemetrexed (25%) in 1L, crizotinib (28%) in 2L, and ceritinib (35%) in 3L. Over two-thirds (68%) received treatment with at least 2 ALKis. The most commonly observed ALKi sequences were crizotinib followed by ceritinib (52%), ceritinib only (23%), and crizotinib followed by ceritinib followed by alectinib (12%). Median OS (95% CI) from mNSCLC diagnosis was 39 (33.1-50.1) months. Median OS (95% CI) from treatment initiation was 36 (28.2-48.9) months for 1L, 29 (22.1-42.8) months for 2L, and 23 (14.0-40.5) months for 3L. Only slightly more than half of patients with ALK-positi..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1272

Authors: J. Mazieres, M. Ahn, C. Chouaid, A. Kron, J. Wolf, R. Goyal, K. Davis, M. Perrinjaquet, T. Pham, S. Knoll

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Conference PaperKirk SmithALK, metastatic NSCLC, Ceritinib
P116-30 Impact of Patient TKI Copayments on Insurance Expenditure in Advanced EGFR or ALK Positive Non-Small Cell Lung Cancer (NSCLC)
P116-30 Impact of Patient TKI Copayments on Insurance Expenditure in Advanced EGFR or ALK Positive Non-Small Cell Lung Cancer (NSCLC)

To influence treatment choice and control expenditures, insurance plans impose cost sharing policies for expensive oral tyrosine kinase inhibitors (TKIs). We evaluated the effect of patient TKI copayments on insurance expenditures among patients with EGFR and ALK positive advanced NSCLC receiving TKIs. The results show that higher TKI copayments were not associated with lower insurance expenditures. Eliminating TKI copayments would reduce patient financial burden and not adversely impact insurer spending. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1256

Authors: B. Haddock Lobo Goulart, S. Chennupati, K. Egan, C. Fedorenko, S. Ramsey

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Conference PaperKirk SmithCopayment, Insurance, Cost