2021
Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer
Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, de Castro Carpeno J, Pluzanski A, Arrieta O, Frontera OA, Chiari R, Butts C, Wójcik-Tomaszewska J, Coudert B, Garassino MC, Ready N, Felip E, García MA, Waterhouse D, Domine M, Barlesi F, Antonia S, Wohlleber M, Gerber DE, Czyzewicz G, Spigel DR, Crino L, Eberhardt WEE, Li A, Marimuthu S, Brahmer J. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2021, 39: 723-733. PMID: 33449799, PMCID: PMC8078445, DOI: 10.1200/jco.20.01605.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LungClinical Trials, Phase III as TopicDisease ProgressionDocetaxelFemaleHumansImmune Checkpoint InhibitorsImmunotherapyLung NeoplasmsMaleMiddle AgedNivolumabProgression-Free SurvivalRandomized Controlled Trials as TopicTime FactorsTubulin ModulatorsYoung AdultConceptsTreatment-related adverse eventsNivolumab-treated patientsProgression-free survivalPhase III trialsOverall survivalCheckMate 017Advanced NSCLCIII trialsOS ratesLung cancerGrade 4 treatment-related adverse eventsFirst-line platinum-based chemotherapyNon-small cell lung cancerRandomized phase III trialEnd pointDeath-1 inhibitorsDocetaxel-treated patientsExploratory landmark analysisPrimary end pointSecondary end pointsFive-year outcomesNew safety signalsPlatinum-based chemotherapyCell lung cancerECOG PS
2019
Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis
Antonia SJ, Borghaei H, Ramalingam SS, Horn L, De Castro Carpeño J, Pluzanski A, Burgio MA, Garassino M, Chow LQM, Gettinger S, Crinò L, Planchard D, Butts C, Drilon A, Wojcik-Tomaszewska J, Otterson GA, Agrawal S, Li A, Penrod JR, Brahmer J. Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis. The Lancet Oncology 2019, 20: 1395-1408. PMID: 31422028, PMCID: PMC7193685, DOI: 10.1016/s1470-2045(19)30407-3.Peer-Reviewed Original ResearchConceptsPD-L1 expressionCell lung cancerOverall survivalCheckMate 017Progressive diseaseHazard ratioSurvival outcomesLung cancerLong-term survival advantageDose of nivolumabTrials of nivolumabNew safety signalsFour-year survivalLonger overall survivalLonger response durationBristol-Myers SquibbStable diseaseAdvanced NSCLCObjective responsePooled analysisLong-term benefitsNivolumabSafety signalsClinical dataClinical studies
2018
FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC
Spigel DR, Chaft JE, Gettinger S, Chao BH, Dirix L, Schmid P, Chow LQM, Hicks RJ, Leon L, Fredrickson J, Kowanetz M, Sandler A, Funke R, Rizvi NA. FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC. Journal Of Thoracic Oncology 2018, 13: 1733-1742. PMID: 29775807, PMCID: PMC7455890, DOI: 10.1016/j.jtho.2018.05.004.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsObjective response ratePD-L1 expressionAdverse eventsCohort 1Immune cell PD-L1 expressionInvestigator-assessed objective response ratePhase II open-label studyResponse rateIC PD-L1 expressionTumor cellsBaseline tumor samplesOpen-label studyPhase II studyProgression-free survivalResponse Evaluation CriteriaDuration of responseAtezolizumab monotherapyAdvanced NSCLCBrain metastasesMonotherapy studiesPrimary endpointSecondary endpointsII studyOverall survivalP1.01-02 Long-Term Outcomes with First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 3-Year Follow-Up from CheckMate 012
Antonia S, Gettinger S, Borghaei H, Goldman J, Brahmer J, Ready N, Gerber D, Chow L, Juergens R, Laurie S, Shepherd F, Li X, Li A, Geese W, Hellmann M. P1.01-02 Long-Term Outcomes with First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 3-Year Follow-Up from CheckMate 012. Journal Of Thoracic Oncology 2018, 13: s458. DOI: 10.1016/j.jtho.2018.08.558.Peer-Reviewed Original ResearchMA15.02 Long-Term Safety and Clinical Activity Results from a Phase Ib Study of Erlotinib Plus Atezolizumab in Advanced NSCLC
Rudin C, Cervantes A, Dowlati A, Besse B, Ma B, Costa D, Schmid P, Heist R, Villaflor V, Sarkar I, Hernandez G, Foster P, Spahn J, O'Hear C, Gettinger S. MA15.02 Long-Term Safety and Clinical Activity Results from a Phase Ib Study of Erlotinib Plus Atezolizumab in Advanced NSCLC. Journal Of Thoracic Oncology 2018, 13: s407. DOI: 10.1016/j.jtho.2018.08.440.Peer-Reviewed Original ResearchNivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC
Gettinger S, Hellmann MD, Chow LQM, Borghaei H, Antonia S, Brahmer JR, Goldman JW, Gerber DE, Juergens RA, Shepherd FA, Laurie SA, Young TC, Li X, Geese WJ, Rizvi N. Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. Journal Of Thoracic Oncology 2018, 13: 1363-1372. PMID: 29802888, DOI: 10.1016/j.jtho.2018.05.015.Peer-Reviewed Original ResearchConceptsAdvanced EGFR-mutant NSCLCEGFR-mutant NSCLCTreatment-related grade 3 toxicitiesEGFR-mutant advanced NSCLCProgression-free survival ratesEGFR T790M mutationEGFR tyrosine kinase inhibitorsGrade 3 toxicityObjective response rateTKI-naive patientsCompound EGFR mutationsT790M mutationTyrosine kinase inhibitorsImmune-related responsesInvestigator recordsAdvanced NSCLCDurable responsesUnacceptable toxicityComplete responseFourth patientDisease progressionEGFR mutationsMutant NSCLCTumor biopsiesNivolumabSafety and clinical activity results from a phase Ib study of alectinib plus atezolizumab in ALK + advanced NSCLC (aNSCLC).
Kim D, Gadgeel S, Gettinger S, Riely G, Oxnard G, Mekhail T, Schmid P, Dowlati A, Heist R, Wozniak A, Hernandez G, Sarkar I, Mitry E, Foster P, O'Hear C, Spahn J, Ou S. Safety and clinical activity results from a phase Ib study of alectinib plus atezolizumab in ALK + advanced NSCLC (aNSCLC). Journal Of Clinical Oncology 2018, 36: 9009-9009. DOI: 10.1200/jco.2018.36.15_suppl.9009.Peer-Reviewed Original ResearchNivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases
Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, Frontera O, Gettinger S, Holgado E, Spigel D, Waterhouse D, Domine M, Garassino M, Chow LQM, Blumenschein G, Barlesi F, Coudert B, Gainor J, Arrieta O, Brahmer J, Butts C, Steins M, Geese WJ, Li A, Healey D, Crinò L. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Annals Of Oncology 2018, 29: 959-965. PMID: 29408986, DOI: 10.1093/annonc/mdy041.Peer-Reviewed Original ResearchConceptsBaseline liver metastasesImproved overall survivalLiver metastasesCell lung cancerOverall survivalOS benefitCheckMate 017Nonsquamous NSCLCLung cancerSubgroup analysisAnti-programmed death-1 (PD-1) antibody nivolumabNivolumab-treated patientsImmune checkpoint inhibitorsPrimary end pointHepatic adverse eventsPhase III trialsFavorable safety profileNew safety concernsCheckMate 057Advanced NSCLCCheckpoint inhibitorsAdverse eventsIII trialsOS ratesAntibody nivolumabFive-Year Follow-Up of Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer: Results From the CA209-003 Study.
Gettinger S, Horn L, Jackman D, Spigel D, Antonia S, Hellmann M, Powderly J, Heist R, Sequist LV, Smith DC, Leming P, Geese WJ, Yoon D, Li A, Brahmer J. Five-Year Follow-Up of Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer: Results From the CA209-003 Study. Journal Of Clinical Oncology 2018, 36: 1675-1684. PMID: 29570421, DOI: 10.1200/jco.2017.77.0412.Peer-Reviewed Original ResearchConceptsLigand 1 expressionOverall survivalAdvanced NSCLCProgressive diseaseOS ratesLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerLong-term OSPhase III studyProportion of patientsResponse Evaluation CriteriaKaplan-Meier methodLong-term survivorsCell lung cancerEarly phase INivolumab 1Nivolumab treatmentStable diseaseNonsquamous NSCLCAdverse eventsDurable responsesFirst doseFormer smokersIII study
2017
OA 17.03 First-Line Nivolumab plus Platinum-Based Doublet Chemotherapy for Advanced NSCLC: CheckMate 012 3-Year Update
Juergens R, Hellmann M, Brahmer J, Borghaei H, Gettinger S, Chow L, Gerber D, Laurie S, Goldman J, Shepherd F, Geese W, Young T, Li X, Antonia S. OA 17.03 First-Line Nivolumab plus Platinum-Based Doublet Chemotherapy for Advanced NSCLC: CheckMate 012 3-Year Update. Journal Of Thoracic Oncology 2017, 12: s1792-s1793. DOI: 10.1016/j.jtho.2017.09.429.Peer-Reviewed Original ResearchNivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012.
Goldman J, Antonia S, Gettinger S, Borghaei H, Brahmer J, Ready N, Gerber D, Chow L, Juergens R, Shepherd F, Laurie S, Geese W, Li A, Li X, Hellmann M. Nivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012. Journal Of Clinical Oncology 2017, 35: 9093-9093. DOI: 10.1200/jco.2017.35.15_suppl.9093.Peer-Reviewed Original ResearchPD-L1 expressionComplete responsePD-L1Long-term OS benefitPD-L1 tumor expressionStage IIIB/IVTumor PD-L1 expressionChemotherapy-naive NSCLCECOG PS 0Experienced grade 3IIIB/IVManageable safety profileFirst-line treatmentPhase 1 studyLong-term survivorsLong-term outcomesMultiple tumor typesExploratory endpointsOS benefitAdvanced NSCLCPrimary endpointSecondary endpointsPS 0Unacceptable toxicityConsent withdrawalOA03.01 First-Line Nivolumab Monotherapy and Nivolumab plus Ipilimumab in Patients with Advanced NSCLC: Long-Term Outcomes from CheckMate 012
Gettinger S, Rizvi N, Chow L, Borghaei H, Brahmer J, Shepherd F, Ready N, Gerber D, Antonia S, Goldman J, Juergens R, Geese W, Young T, Li X, Hellmann M. OA03.01 First-Line Nivolumab Monotherapy and Nivolumab plus Ipilimumab in Patients with Advanced NSCLC: Long-Term Outcomes from CheckMate 012. Journal Of Thoracic Oncology 2017, 12: s250-s251. DOI: 10.1016/j.jtho.2016.11.238.Peer-Reviewed Original ResearchOA03.02 Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS and OS Data from the BIRCH Study
Garassino M, Rizvi N, Besse B, Jänne P, Christoph D, Peters S, Toh C, Kurata T, Costa E, Koczywas M, Felip E, Chaft J, Qiu J, Kowanetz M, Coleman S, Mocci S, Sandler A, Gettinger S, Johnson M. OA03.02 Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS and OS Data from the BIRCH Study. Journal Of Thoracic Oncology 2017, 12: s251-s252. DOI: 10.1016/j.jtho.2016.11.239.Peer-Reviewed Original Research
2016
441O Preliminary safety and clinical activity of erlotinib plus atezolizumab from a Phase Ib study in advanced NSCLC
Ma B, Rudin C, Cervantes A, Dowlati A, Costa D, Schmid P, Heist R, Villaflor V, Sarkar I, Huseni M, Foster P, O’Hear C, Gettinger S, Besse B. 441O Preliminary safety and clinical activity of erlotinib plus atezolizumab from a Phase Ib study in advanced NSCLC. Annals Of Oncology 2016, 27: ix141. DOI: 10.1016/s0923-7534(21)00599-8.Peer-Reviewed Original Research441O Preliminary safety and clinical activity of erlotinib plus atezolizumab from a Phase Ib study in advanced NSCLC
Ma B, Rudin C, Cervantes A, Dowlati A, Costa D, Schmid P, Heist R, Villaflor V, Sarkar I, Huseni M, Foster P, O'Hear C, Gettinger S, Besse B. 441O Preliminary safety and clinical activity of erlotinib plus atezolizumab from a Phase Ib study in advanced NSCLC. Annals Of Oncology 2016, 27 DOI: 10.1093/annonc/mdw594.005.Peer-Reviewed Original ResearchORAL01.04: Phase II Trial of Atezolizumab for Patients with PD-L1–Selected Advanced NSCLC (BIRCH): Updated Efficacy and Exploratory Biomarker Results Topic: Medical Oncology
Wakelee H, Patel J, Heist R, Balmanoukian A, Besse B, Felip E, Costa E, Chow L, Koczywas M, Garassino M, Christoph D, Toh C, Johnson M, Chaft J, Kurata T, Qiu J, Kowanetz M, Coleman S, Mocci S, Sandler A, Gettinger S, Peters S. ORAL01.04: Phase II Trial of Atezolizumab for Patients with PD-L1–Selected Advanced NSCLC (BIRCH): Updated Efficacy and Exploratory Biomarker Results Topic: Medical Oncology. Journal Of Thoracic Oncology 2016, 11: s251-s252. DOI: 10.1016/j.jtho.2016.09.009.Peer-Reviewed Original ResearchThe BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Papadimitrakopoulou V, Lee JJ, Wistuba II, Tsao AS, Fossella FV, Kalhor N, Gupta S, Byers LA, Izzo JG, Gettinger SN, Goldberg SB, Tang X, Miller VA, Skoulidis F, Gibbons DL, Shen L, Wei C, Diao L, Peng SA, Wang J, Tam AL, Coombes KR, Koo JS, Mauro DJ, Rubin EH, Heymach JV, Hong WK, Herbst RS. The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2016, 34: 3638-3647. PMID: 27480147, PMCID: PMC5065110, DOI: 10.1200/jco.2015.66.0084.Peer-Reviewed Original ResearchDisease control rateKRAS wild-type patientsMedian overall survivalProgression-free survivalWild-type patientsArm 1Overall survivalKRAS statusArm 3Lung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerBiomarker-driven treatment strategiesLung Cancer Elimination (BATTLE) trialMedian progression-free survivalImproved progression-free survivalBiomarker-Integrated ApproachesReal-time biopsyPrimary end pointCell lung cancerPrior therapyUmbrella studyAdvanced NSCLCControl rateMesenchymal tumorsP2.36: Nivolumab (nivo) in Patients (pts) With Advanced (adv) NSCLC and Central Nervous System (CNS) Metastases (mets) Track: Immunotherapy
Goldman J, Crino L, Vokes E, Holgado E, Reckamp K, Pluzanski A, Spigel D, Kohlhaeufl M, Garassino M, Chow L, Gettinger S, Gerber D, Havel L, Ramalingam S, Dy G, Geese W, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Lopes G. P2.36: Nivolumab (nivo) in Patients (pts) With Advanced (adv) NSCLC and Central Nervous System (CNS) Metastases (mets) Track: Immunotherapy. Journal Of Thoracic Oncology 2016, 11: s238-s239. DOI: 10.1016/j.jtho.2016.08.107.Peer-Reviewed Original ResearchNivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Gettinger S, Rizvi NA, Chow LQ, Borghaei H, Brahmer J, Ready N, Gerber DE, Shepherd FA, Antonia S, Goldman JW, Juergens RA, Laurie SA, Nathan FE, Shen Y, Harbison CT, Hellmann MD. Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2016, 34: 2980-2987. PMID: 27354485, PMCID: PMC5569692, DOI: 10.1200/jco.2016.66.9929.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsObjective response ratePD-ligand 1 (PD-L1) expressionAdverse eventsOverall survivalNivolumab monotherapyAdvanced NSCLCLung cancerGrade 3Death-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerGrade treatment-related adverse eventsNon-small cell lung cancerImmune checkpoint inhibitor antibodyProgression-free survival ratesCheckpoint inhibitor antibodyExploratory end pointsFirst tumor assessmentFirst-line monotherapyOngoing complete responseTolerable safety profileMedian overall survivalGrade 3 rashOnly grade 3Cell lung cancerCheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC.
Hellmann M, Gettinger S, Goldman J, Brahmer J, Borghaei H, Chow L, Ready N, Gerber D, Juergens R, Shepherd F, Laurie S, Zhou Y, Geese W, Agrawal S, Li X, Antonia S. CheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC. Journal Of Clinical Oncology 2016, 34: 3001-3001. DOI: 10.1200/jco.2016.34.15_suppl.3001.Peer-Reviewed Original Research