2025
Precision projections of the delay of resistance mutations in non-small cell lung cancer via suppression of APOBEC
Nousias O, Mandell J, Anderson K, Townsend J. Precision projections of the delay of resistance mutations in non-small cell lung cancer via suppression of APOBEC. Lung Cancer 2025, 202: 108487. PMID: 40090261, DOI: 10.1016/j.lungcan.2025.108487.Peer-Reviewed Original ResearchNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsCell lung cancerLung cancer patientsEvolution of drug resistanceLung cancerDrug resistanceCancer patientsTyrosine kinase inhibitor therapyKinase inhibitor therapyTyrosine kinase inhibitorsPersonalized therapeutic strategiesTKI therapyInhibitor therapyTherapeutic failureResistance mutationsTherapeutic efficacyKinase inhibitorsAPOBEC mutationsTherapeutic strategiesTreatment efficacyCancer progressionImprove outcomesCancerHow to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology
Khattab M, Baig M, Zarif T, Barac A, Ferencik M, Henry M, Lopez-Mattei J, Redheuil A, Salem J, Scherrer-Crosbie M, Yang E, Baldassarre L. How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology. Circulation Cardiovascular Imaging 2025, 18: e015981. PMID: 39772610, DOI: 10.1161/circimaging.124.015981.Peer-Reviewed Original ResearchConceptsCardio-oncologyCases of atherosclerosisCardiac magnetic resonance imagingCoronary computed tomography angiographySingle-photon emission computed tomographyImmune checkpoint inhibitorsLeft ventricular dysfunctionMultimodality cardiac imagingTyrosine kinase inhibitorsCardiac imaging modalitiesComputed tomography angiographyRisk of cardiovascular diseaseEmission computed tomographyPositron emission tomographyMagnetic resonance imagingCheckpoint inhibitorsVentricular dysfunctionMyocardial inflammationCoronary vasospasmAccelerated atherosclerosisKinase inhibitorsPatient populationDiagnosing such pathologiesCancer therapyCardiac imaging
2024
Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia.
Huntington S, Rhodes J, Manzoor B, Jawaid D, Puckett J, Emechebe N, Ravelo A, Kamal-Bahl S, Marx S, Doshi J. Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia. JCO Oncology Practice 2024, op2400220. PMID: 39705617, DOI: 10.1200/op.24.00220.Peer-Reviewed Original ResearchChronic lymphocytic leukemia treatmentChronic lymphocytic leukemiaFollow-up periodFrontline settingLymphocytic leukemiaTreatment patternsFollow-upReal-world treatment patternsMedian time to discontinuationBruton tyrosine kinase inhibitorAnti-CD20 monotherapyPatients discontinued treatmentMonths of treatmentTime to discontinuationTyrosine kinase inhibitorsReal-world studyPatient-monthsBTKiTreatment optionsVenetoclaxKinase inhibitorsPatientsAll-causeBcl-2MonthsA Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer
Jia J, Moyer A, Lowe M, Bolch E, Kortmansky J, Cho M, Lenz H, Kalyan A, Niedzwiecki D, Strickler J. A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. Journal Of Gastrointestinal Cancer 2024, 56: 29. PMID: 39652198, DOI: 10.1007/s12029-024-01156-x.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsMetastatic colorectal cancerPhase 2 studyEpidermal growth factor receptorAnti-tumor activityStable diseaseProgressive diseaseChemotherapy refractory metastatic colorectal cancerOral small-molecule tyrosine kinase inhibitorColorectal cancerResistance to epidermal growth factor receptorSmall molecule tyrosine kinase inhibitorsRefractory metastatic colorectal cancerBest overall responseRAS wild-typeAdvanced solid tumorsBiomarker-selected patientsTyrosine kinase inhibitorsWild-typeGrowth factor receptorResultsFive patientsPrimary endpointSecondary endpointsSolid tumorsSavolitinib156. Safety of Remibrutinib across Immune-mediated Diseases Supports Development in Multiple Sclerosis
Kieseier B, Montalban X, Williams M, Airas L, Saini S, Hide M, Sussman G, Nakahara J, Bermel R, Dörner T, Loop B, DeLasHeras V, Willi R, Haemmerle S, Zharkov A, Barbier N, Azmon A, Siegel R, Cenni B, Haddad I, Wiendl H, Maurer M, Giménez-Arnau A, Chitnis T. 156. Safety of Remibrutinib across Immune-mediated Diseases Supports Development in Multiple Sclerosis. Multiple Sclerosis And Related Disorders 2024, 92: 106117. DOI: 10.1016/j.msard.2024.106117.Peer-Reviewed Original ResearchAdverse eventsSafety profileOral Bruton's tyrosine kinase inhibitorTreatment of relapsing multiple sclerosisBruton tyrosine kinase inhibitorSkin/subcutaneous tissue disordersUpper respiratory tract infectionMultiple sclerosisTyrosine kinase inhibitorsPhase 3 trialRespiratory tract infectionsGrouped adverse eventsIntegrated safety analysisNervous system disordersTreatment discontinuationTract infectionsRemibrutinibTissue disordersKinase inhibitorsSystem disordersOff-target effectsGastrointestinal disordersDoseInfectionPooled dataThe Incidence of CNS Relapse in Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) and Its Impact on Clinical Outcome: Results from Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Shah K, El Kettani M, Narra R, Mims A, Coltoff A, Medawar G, Hisrich B, Shallis R, Hunter C, Kota V, Othman T, Jonas B, Desai S, Sacchi de Camargo Correia G, Patel A, Duvall A, Palmisiano N, Curran E, Omer Z, Advani A, Atallah E, Litzow M, Badar T. The Incidence of CNS Relapse in Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) and Its Impact on Clinical Outcome: Results from Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood 2024, 144: 4184-4184. DOI: 10.1182/blood-2024-205812.Peer-Reviewed Original ResearchCNS relapseCentral nervous system involvementPh+ acute lymphoblastic leukemiaRelapse free survivalTyrosine kinase inhibitorsAcute lymphoblastic leukemiaIncidence of CNS relapseMedian relapse free survivalCentral nervous systemCNS diseaseOverall survivalAllo-HCTIntrathecal chemotherapyWhite blood cellsIntensive chemotherapyPost-relapseT315I mutationBaseline characteristicsMedian time to CNS relapseAllogeneic stem cell transplantationAssociated with significant toxicityIncidence of CNS diseaseMedian white blood cellAdequate CNS prophylaxisCentral nervous system penetrationNivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
Wu J, Zhang S, Yu S, An G, Wang Y, Yu Y, Liang L, Wang Y, Xu X, Xiong Y, Shao D, Shi Z, Li N, Wang J, Jin D, Liu T, Cui Y. Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial. Nature Communications 2024, 15: 8876. PMID: 39406730, PMCID: PMC11480398, DOI: 10.1038/s41467-024-53109-4.Peer-Reviewed Original ResearchConceptsEsophageal squamous cell carcinomaAdvanced gastric adenocarcinomaSquamous cell carcinomaTyrosine kinase inhibitorsGastric adenocarcinomaVariant allele frequencyAnlotinib hydrochlorideCell carcinomaVascular endothelial growth factor inhibitorsAnti-PD-1 antibodySafety of nivolumabAnti-PD-1Disease control rateMedian overall survivalProgression-free survivalGrowth factor inhibitorsPhase II trialOverall response rateOASIS trialPD-1Second-lineOverall survivalImmune signaturesII trialFactor inhibitorsTreatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib
Robinson N, Canavan M, Zhan P, Udelsman B, Pathak R, Boffa D, Goldberg S. Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib. Clinical Lung Cancer 2024, 26: 9-17.e3. PMID: 39462746, DOI: 10.1016/j.cllc.2024.09.006.Peer-Reviewed Original ResearchNon-small cell lung cancerEGFR-mutant non-small cell lung cancerFirst-line osimertinibContinuation of osimertinibImmune checkpoint inhibitorsTyrosine kinase inhibitorsCell lung cancerRetrospective cohort studyOverall survivalTreatment regimensLung cancerAdvanced epidermal growth factor receptorAssociated with increased PFSAssociated with superior PFSSecond-line treatment regimenEGFR exon 19 deletionRetrospective cohort study of patientsEGFR tyrosine kinase inhibitorsAssociated with prolonged survivalCohort study of patientsSecond-line treatment regimensExon 19 deletionFirst-line therapyEpidermal growth factor receptorFirst-line treatmentReal-World Healthcare Costs Among Patients With Chronic Lymphocytic Leukemia Receiving First-Line Treatment With Venetoclax + Obinutuzumab Versus Bruton Tyrosine Kinase Inhibitors
Ravelo A, Patel A, To T, Li S, Huntington S. Real-World Healthcare Costs Among Patients With Chronic Lymphocytic Leukemia Receiving First-Line Treatment With Venetoclax + Obinutuzumab Versus Bruton Tyrosine Kinase Inhibitors. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s180. DOI: 10.1016/s2152-2650(24)00569-x.Peer-Reviewed Original ResearchCLL-144 Real-World Healthcare Costs Among Patients With Chronic Lymphocytic Leukemia Receiving First-Line Treatment With Venetoclax + Obinutuzumab Versus Bruton Tyrosine Kinase Inhibitors
Ravelo A, Patel A, To T, Li S, Huntington S. CLL-144 Real-World Healthcare Costs Among Patients With Chronic Lymphocytic Leukemia Receiving First-Line Treatment With Venetoclax + Obinutuzumab Versus Bruton Tyrosine Kinase Inhibitors. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s345. DOI: 10.1016/s2152-2650(24)01263-1.Peer-Reviewed Original ResearchPer-patient per-monthPer-patient per-month costsChronic lymphocytic leukemiaBruton tyrosine kinase inhibitorFirst-line treatmentTyrosine kinase inhibitorsLymphocytic leukemiaMonths 0Kinase inhibitorsHealthcare costsCLL/small lymphocytic lymphomaFixed-duration treatmentFirst-line therapyOff-treatment periodMonths post-indexMonths pre-indexRetrospective observational studyClinical trial enrollmentUS health planCommercially insured patientsLymphocytic lymphomaPrimary cancerFirst-linePost-indexIbrutinibChitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer
Kamle S, Ma B, Schor G, Bailey M, Pham B, Cho I, Khan H, Azzoli C, Hofstetter M, Sadanaga T, Herbst R, Politi K, Lee C, Elias J. Chitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer. Translational Oncology 2024, 49: 102108. PMID: 39178575, PMCID: PMC11388375, DOI: 10.1016/j.tranon.2024.102108.Peer-Reviewed Original ResearchNon-small cell lung cancerEpidermal growth factor receptorTyrosine kinase inhibitorsEpidermal growth factor receptor mutant non-small cell lung cancerMutant non-small cell lung cancerEpidermal growth factor receptor axisCell lung cancerLung cancerTherapeutic resistanceDownstream targets of EGFRResistance to TKI therapyEpithelial cellsStimulated epidermal growth factor receptorWild type epidermal growth factor receptorTargeting of epidermal growth factor receptorActivating EGFR mutationsChitinase 3-like 1Progression free survivalInduce tumor cell deathEpidermal growth factor receptor activationEffects of EGFR activationInhibited pulmonary metastasisTumor cell deathResponse to treatmentGrowth factor receptorReal-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries
Lee C, Yoo C, Hong J, Park J, Kim J, Tai D, Kim H, Korphaisarn K, Tanasanvimon S, Chen S, Kim J, Kim I, Kim M, Choo J, Oh S, Chen C, Bae W, Kim H, Huh S, Yen C, Park S, Lee D, Chan L, Kang B, Kang M, Sundar R, Choi H, Chan S, Chon H, Lee M. Real-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries. Liver Cancer 2024, 1-15. DOI: 10.1159/000540969.Peer-Reviewed Original ResearchFirst-line atezolizumabProgression-free survivalImmune checkpoint inhibitorsTyrosine kinase inhibitorsSecond-line regimensOverall survivalHepatocellular carcinomaSecond-line progression-free survivalSecond-line tyrosine kinase inhibitorsPatients treated with tyrosine kinase inhibitorsAssociated with improved OSImmune checkpoint inhibitor combinationsImmune checkpoint inhibitor useMedian progression-free survivalLow tumor burdenAdvanced hepatocellular carcinomaFirst-line regimenReal-world studyCheckpoint inhibitorsTumor burdenSystemic treatmentAtezolizumabBevacizumabRetrospective studyLenvatinibGastrointestinal Cancer Therapy and Cardiotoxicity
Leiva O, Zarif T, Alvarez-Cardona J. Gastrointestinal Cancer Therapy and Cardiotoxicity. Current Treatment Options In Oncology 2024, 25: 1203-1209. PMID: 39102169, DOI: 10.1007/s11864-024-01236-x.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsGastrointestinal cancerAnti-vascular endothelial growth factorHeterogeneous group of cancersCancer-specific outcomesEndothelial growth factorGroup of cancersConventional chemotherapyCardiotoxic therapiesTargeted therapyPotential cardiotoxicityKinase inhibitorsRisk factorsCardiovascular diseaseGrowth factorCancerHeterogeneous groupTherapyCardiotoxicityImmunotherapyChemotherapyPatientsReal-world comparison of health care costs of venetoclax-obinutuzumab vs Bruton's tyrosine kinase inhibitor use among US Medicare beneficiaries with chronic lymphocytic leukemia in the frontline setting.
Huntington S, Manzoor B, Jawaid D, Puckett J, Emechebe N, Ravelo A, Kamal-Bahl S, Doshi J. Real-world comparison of health care costs of venetoclax-obinutuzumab vs Bruton's tyrosine kinase inhibitor use among US Medicare beneficiaries with chronic lymphocytic leukemia in the frontline setting. Journal Of Managed Care & Specialty Pharmacy 2024, 30: 1106-1116. PMID: 39046941, PMCID: PMC11424914, DOI: 10.18553/jmcp.2024.24049.Peer-Reviewed Original ResearchChronic lymphocytic leukemiaMonths 0Frontline settingSample of older US adultsMedicare beneficiariesLymphocytic leukemiaFee-for-service Medicare beneficiariesTreatment periodStudy of older adultsTyrosine kinase inhibitor useOlder US adultsBruton tyrosine kinase inhibitorFixed-duration therapyUS Medicare beneficiariesFee-for-serviceMonthly costTyrosine kinase inhibitorsHealth care costsMedicare Part ABcl-2 inhibitorsMultivariate general linear modelMonthly total costsTotal monthly costsPrescription drug costsComparison of health care costsTyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)
Pike L, Miao E, Boe L, Patil T, Imber B, Myall N, Pollom E, Hui C, Qu V, Langston J, Chiang V, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Braunstein S, Kavanagh B, Camidge D, Rusthoven C. Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 3606-3617. PMID: 39047224, PMCID: PMC11874932, DOI: 10.1200/jco.23.02668.Peer-Reviewed Original ResearchNon-small cell lung cancerUp-front stereotactic radiosurgeryTyrosine kinase inhibitorsALK-driven NSCLCStereotactic radiosurgeryBrain metastasesCell lung cancerOverall survivalCNS controlLung cancerOncogene-driven non-small cell lung cancerKinase inhibitorsCNS progression-free survivalStereotactic radiosurgery groupTKI-naive patientsProgression-free survivalAnaplastic lymphoma kinaseEpidermal growth factor receptorCox proportional hazards modelsGrowth factor receptorClinically relevant factorsProportional hazards modelMedian OSNo significant differenceNeurological symptomsPhase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A
Gettinger S, Song Z, Reckamp K, Moscow J, Gray R, Wang V, McShane L, Rubinstein L, Patton D, Williams P, Hamilton S, Kong X, Tricoli J, Conley B, Arteaga C, Harris L, O'Dwyer P, Chen A, Flaherty K. Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A. JCO Precision Oncology 2024, 8: e2300725. PMID: 38986051, DOI: 10.1200/po.23.00725.Peer-Reviewed Original ResearchConceptsProgression-free survivalTyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsNCI-MATCHLung cancerGlioblastoma multiformeOverall survivalAdvanced non-small cell lung cancerNational Cancer Institute-Molecular AnalysisNon-small cell lung cancerEnd pointsTumor genomic testingTrial primary end pointPhase 2 trialPhase II trialSecondary end pointsPrimary end pointCell lung cancerCohort of patientsMedian OSStable diseaseAdenosquamous carcinomaProtocol therapyPartial responseArm AReal-World Treatment Patterns, Survival, and Economic Burden Among Elderly MCL Patients Previously Treated With cBTKis
Squires P, Puckett J, Ryland K, Kamal-Bahl S, Raut M, Doshi J, Huntington S. Real-World Treatment Patterns, Survival, and Economic Burden Among Elderly MCL Patients Previously Treated With cBTKis. Clinical Lymphoma Myeloma & Leukemia 2024, 24: e350-e358.e1. PMID: 39034204, DOI: 10.1016/j.clml.2024.05.023.Peer-Reviewed Original ResearchR/R MCLOverall survivalTreatment patternsRelapsed/refractory mantle cell lymphomaReal-world treatment patternsBruton tyrosine kinase inhibitorCovalent Bruton tyrosine kinase inhibitorMantle cell lymphomaTyrosine kinase inhibitorsDevelopment of novel therapeuticsMCL patientsCell lymphomaThird-lineRetrospective studyTreatment initiationResponse durationAdverse eventsElderly patientsKinase inhibitorsPatient subpopulationsPatientsAll-causeNovel therapeuticsEconomic burdenSurvivalTucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results.
O'Brien B, Murthy R, Berry D, Singareeka Raghavendra A, Gule-Monroe M, Johnson J, Schwartz-Gomez J, Topletz-Erickson A, Lobbous M, Melisko M, Morikawa A, Ferguson S, de Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Stringer-Reasor E. Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. Journal Of Clinical Oncology 2024, 42: 2018-2018. DOI: 10.1200/jco.2024.42.16_suppl.2018.Peer-Reviewed Original ResearchHER2+ breast cancerLeptomeningeal metastasesPatient-reported outcomesBreast cancerObjective responseClinical examCSF cytologyEvidence of clinically meaningful benefitHER2-targeted tyrosine kinase inhibitorsMedian time to CNS progressionMetastatic HER2+ breast cancerKarnofsky performance status >Treatment of leptomeningeal metastasesAbnormal CSF cytologyPerformance status >Targeted neurological deficitsMDASI-BTPhase 2 studyTyrosine kinase inhibitorsClinically meaningful benefitPre-specified timepointsPreliminary efficacy dataCNS progressionMedian OSCNS metastasesTyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC).
Miao E, Pike L, Boe L, Patil T, Myall N, Hui C, Pollom E, Qu V, Langston J, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Camidge D, Rusthoven C. Tyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 2019-2019. DOI: 10.1200/jco.2024.42.16_suppl.2019.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsUpfront stereotactic radiosurgeryCentral nervous systemTKI-naive patientsStereotactic radiosurgeryOverall survivalMultivariable adjustmentCNS controlNeurological symptomsCNS objective response rateOncogene-driven non-small cell lung cancerFirst-generation TKIsKinase inhibitorsUpfront tyrosine kinase inhibitorNon-small cell lung cancerCentral nervous system radiationGeneration tyrosine kinase inhibitorsEGFR-mutant NSCLCMulti-institutional seriesObjective response rateInferior overall survivalMedian follow-upTreatment of BMCell lung cancerCox proportional hazards modelsOverall survival (OS) in a u.s. Asian population with stage IV NSCLC with EGFR mutations treated with first-line (1L) osimertinib (Osi) compared to earlier generation (Gen) of TKIs or sequential treatment (Tx).
Liu Y, Ma Z, Moreira A, Chachoua A, Velcheti V, Lau S, Punekar S, Sabari J, Shum E. Overall survival (OS) in a u.s. Asian population with stage IV NSCLC with EGFR mutations treated with first-line (1L) osimertinib (Osi) compared to earlier generation (Gen) of TKIs or sequential treatment (Tx). Journal Of Clinical Oncology 2024, 42: e20597-e20597. DOI: 10.1200/jco.2024.42.16_suppl.e20597.Peer-Reviewed Original ResearchNon-small-cell lung cancerTyrosine kinase inhibitorsStage IV non-small-cell lung cancerIV non-small-cell lung cancerOverall survivalCox proportional-hazards modelRetrospective studyProportional-hazards modelMedian OSMetastatic non-small-cell lung cancerHazard ratioIRB-approved retrospective studyMultivariate Cox proportional-hazards modelProgression-free survivalYears of follow-upKaplan-Meier methodLog-rank testAssess survival differencesCalculate hazard ratiosFLAURA trialL858R patientsNSCLC ptsSequential afatinibSuperior OSEGFR mutations
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