2024
Contribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119
Cortes J, Winer E, Lipatov O, Im S, Gonçalves A, Muñoz‐Couselo E, Lee K, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Hund S, Kulangara K, Karantza V, Mejia J, Ma J, Jelinic P, Huang L, Pruitt S, Emancipator K. Contribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119. The Journal Of Pathology Clinical Research 2024, 10: e12371. PMID: 38627977, PMCID: PMC11021797, DOI: 10.1002/2056-4538.12371.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerPD-L1 expressionTriple-negative breast cancerPD-L1 CPSPD-L1Breast cancerTreated metastatic triple-negative breast cancerIncreased programmed death ligand 1PD-L1 IHC 22C3 pharmDxEfficacy of pembrolizumab monotherapyPD-L1 expression assessmentProgrammed death-1 blockadeExpression of PD-L1Objective response rateProgression-free survivalTumor proportion scoreDeath-ligand 1Contribution of tumorImmune cell densityReceiver operating characteristic curveArea under the receiver operating characteristic curvePredictive of responsePembrolizumab monotherapyOverall survivalUniform scoring system
2023
Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study
Schmid P, Lipatov O, Im S, Goncalves A, Muñoz-Couselo E, Lee K, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Mejia J, Zhou X, Haiderali A, Nguyen A, Cortes J, Winer E. Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study. European Journal Of Cancer 2023, 195: 113393. PMID: 37976633, DOI: 10.1016/j.ejca.2023.113393.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCombined positive scoreMetastatic triple-negative breast cancerPD-L1 combined positive scoreHealth-related qualityBreast cancerQLQ-C30 functional scalesTumor PD-L1 expressionGHS/QoLNausea/vomitingPD-L1 expressionStart of treatmentHRQoL resultsEligible patientsHRQoL analysisOverall survivalSystemic therapyClinical outcomesFunctional scalesPhysician's choicePatientsChemotherapyFirst onsetCountry guidelinesMedian TTD190MO Association of 18-Gene expression profile (GEP) with clinical outcomes in patients with metastatic triple-negative breast cancer (mTNBC) treated with pembrolizumab (Pembro) or chemotherapy (Chemo) in KEYNOTE-119
Cortés J, Lipatov O, Im S, Gonçalves A, Lee K, Schmid P, Tamura K, Testa L, Ohtani S, Harbeck N, Loi S, Salgado R, Lunceford J, Karantza V, Mejia J, Cristescu R, Nebozhyn M, Jelinic P, Huang L, Winer E. 190MO Association of 18-Gene expression profile (GEP) with clinical outcomes in patients with metastatic triple-negative breast cancer (mTNBC) treated with pembrolizumab (Pembro) or chemotherapy (Chemo) in KEYNOTE-119. ESMO Open 2023, 8: 101379. DOI: 10.1016/j.esmoop.2023.101379.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTriple-negative breast cancerClinical outcomesBreast cancerExpression profilesPembrolizumabChemotherapyPatientsCancerAssociation Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis
Loi S, Salgado R, Schmid P, Cortes J, Cescon D, Winer E, Toppmeyer D, Rugo H, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan A, Sun Y, Karantza V, Wang A, Huang L, Saadatpour A, Cristescu R, Yearley J, Lunceford J, Jelinic P, Adams S. Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. JCO Precision Oncology 2023, 7: e2200317. PMID: 37099733, DOI: 10.1200/po.22.00317.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerClinical outcomesPembrolizumab monotherapyPD-L1Metastatic diseaseGEP signaturesBreast cancerStromal tumor-infiltrating lymphocytesT-cell-inflamed gene expression profileExploratory biomarker analysisMore systemic therapiesPD-L1 CPSTumor PD-L1PD-L1 statusTumor-infiltrating lymphocytesImproved clinical outcomesTumor mutational burdenSignature 3Mutational signature 3Cohort BDifferentiation 8Systemic therapyCohort ACombined cohort
2022
Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit.
Barroso-Sousa R, Forman J, Collier K, Weber ZT, Jammihal TR, Kao KZ, Richardson ET, Keenan T, Cohen O, Manos MP, Brennick RC, Ott PA, Hodi FS, Dillon DA, Attaya V, O'Meara T, Lin NU, Van Allen EM, Rodig S, Winer EP, Mittendorf EA, Wu CJ, Wagle N, Stover DG, Shukla SA, Tolaney SM. Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit. JCO Precision Oncology 2022, 6: e2100413. PMID: 35797509, PMCID: PMC9848556, DOI: 10.1200/po.21.00413.Peer-Reviewed Original ResearchConceptsGene expression pathwaysMetastatic triple-negative breast cancerExpression pathwaysWhole-exome sequencingFollicular helper T cellsDNA damage repair pathwaysTriple-negative breast cancerProgression-free survivalMemory T cellsDamage repair pathwaysHelper T cellsTumor mutational burdenT cellsClonal evolutionOverall survivalDNA whole-exome sequencingTranscriptomic landscapeHomologous recombinationRepair pathwaysRNA sequencingM1 macrophagesBreast cancerDefective repairMutational burdenDNA damage
2021
Association of 17q22 Amplicon Via Cell-Free DNA With Platinum Chemotherapy Response in Metastatic Triple-Negative Breast Cancer
Collier KA, Asad S, Tallman D, Jenison J, Rajkovic A, Mardis ER, Parsons HA, Tolaney SM, Winer EP, Lin NU, Ha G, Adalsteinsson VA, Stover DG. Association of 17q22 Amplicon Via Cell-Free DNA With Platinum Chemotherapy Response in Metastatic Triple-Negative Breast Cancer. JCO Precision Oncology 2021, 5: po.21.00104. PMID: 34849445, PMCID: PMC8624042, DOI: 10.1200/po.21.00104.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerProgression-free survivalTriple-negative breast cancerPlatinum chemotherapyCancer Genome AtlasBreast cancerBreast Cancer International Consortium data setLonger median progression-free survivalMedian progression-free survivalPlatinum-based chemotherapy regimenSomatic copy number alterationsCopy number alterationsCox proportional hazards modelPlatinum chemotherapy responseTriple negative breast cancer tumorsSpecific somatic copy number alterationsGenome AtlasBreast Cancer International ConsortiumProportional hazards modelBreast cancer tumorsWarrants further investigationCell-free DNAEvaluable patientsChemotherapy regimenMetastatic settingCorrigendum to ‘First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis’ Annals of Oncology 2021; 32: 983-993
Emens LA, Adams S, Barrios CH, Diéras V, Iwata H, Loi S, Rugo HS, Schneeweiss A, Winer EP, Patel S, Henschel V, Swat A, Kaul M, Molinero L, Patel S, Chui SY, Schmid P. Corrigendum to ‘First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis’ Annals of Oncology 2021; 32: 983-993. Annals Of Oncology 2021, 32: 1650. PMID: 34740469, DOI: 10.1016/j.annonc.2021.10.002.Peer-Reviewed Original ResearchNivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
Barroso-Sousa R, Keenan TE, Li T, Tayob N, Trippa L, Pastorello RG, Richardson III ET, Dillon D, Amoozgar Z, Overmoyer B, Schnitt SJ, Winer EP, Mittendorf EA, Van Allen E, Duda DG, Tolaney SM. Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study. Npj Breast Cancer 2021, 7: 110. PMID: 34433812, PMCID: PMC8387440, DOI: 10.1038/s41523-021-00287-9.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTumor-infiltrating lymphocytesTriple-negative breast cancerObjective response ratePD-L1Primary endpointBreast cancerSingle-arm phase II studyHigh tumor-infiltrating lymphocytesLow tumor mutational burdenSafety of cabozantinibPhase II studyImmune checkpoint moleculesHigher pretreatment levelsTumor mutational burdenImmune gene expressionRECIST 1.1Checkpoint moleculesII studyImmunosuppressive cytokinesPartial responseNegative tumorsPositive tumorsTumor immunosuppressionRapid progressionCorrigendum to ‘First-line atezolizumab plus nab-paclitaxel for unresectable locally advanced or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis’ Annals of Oncology 2021; volume 32: 983–993
Emens LA, Adams S, Barrios CH, Diéras V, Iwata H, Loi S, Rugo HS, Schneeweiss A, Winer EP, Patel S, Henschel V, Swat A, Kaul M, Molinero L, Patel S, Chui SY, Schmid P. Corrigendum to ‘First-line atezolizumab plus nab-paclitaxel for unresectable locally advanced or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis’ Annals of Oncology 2021; volume 32: 983–993. Annals Of Oncology 2021, 32: 1308. PMID: 34353668, DOI: 10.1016/j.annonc.2021.07.013.Peer-Reviewed Original ResearchContribution of tumour and immune cells to PD-L1 as a predictive biomarker in metastatic triple-negative breast cancer (mTNBC): analysis from keynote-119
Emancipator K, Winer E, Lipatov O, Im S, Goncalves A, Muñoz-Couselo E, Lee K, Nowecki Z, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Hund S, Kulangara K, Karantza V, Mejia J, Ma J, Jelinic P, Huang L, Cortes J. Contribution of tumour and immune cells to PD-L1 as a predictive biomarker in metastatic triple-negative breast cancer (mTNBC): analysis from keynote-119. Pathology 2021, 53: s47-s48. DOI: 10.1016/j.pathol.2021.06.099.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTriple-negative breast cancerContribution of tumorPD-L1Predictive biomarkersImmune cellsBreast cancerTumorsCancerBiomarkersFirst-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis
Emens LA, Adams S, Barrios CH, Diéras V, Iwata H, Loi S, Rugo HS, Schneeweiss A, Winer EP, Patel S, Henschel V, Swat A, Kaul M, Molinero L, Patel S, Chui SY, Schmid P. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Annals Of Oncology 2021, 32: 983-993. PMID: 34272041, DOI: 10.1016/j.annonc.2021.05.355.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerPD-L1 (+) immune cellsTriple-negative breast cancerOverall survivalImmune cellsITT populationOS benefitNab-paclitaxelBreast cancerFinal overall survival analysisTumor-infiltrating immune cellsFinal overall survivalFirst-line atezolizumabMedian overall survivalFirst-line treatmentProgression-free survivalOverall survival analysisPrespecified analysis planMedian OSCoprimary endpointsAdverse eventsPositive patientsUnacceptable toxicitySafety outcomesToxicity profileSaci-IO TNBC: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1– metastatic triple-negative breast cancer (mTNBC).
Garrido-Castro A, Keenan T, Li T, Lange P, Callahan C, Guerriero J, Tayob N, Anderson L, Yam C, Daniel B, Carey L, Nanda R, Winer E, Mittendorf E, Tolaney S. Saci-IO TNBC: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1– metastatic triple-negative breast cancer (mTNBC). Journal Of Clinical Oncology 2021, 39: tps1106-tps1106. DOI: 10.1200/jco.2021.39.15_suppl.tps1106.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalRandomized phase II trialPhase II trialSacituzumab govitecanPD-L1II trialImmune cellsBreast cancerAnti-PD-1/L1 antibodyPD-1/L1 inhibitorsAntibody-dependent cellular cytotoxicityT cell effector functionTriple-negative breast cancerPrior systemic therapyPD-L1 expressionAntitumor immune responseChronic antigen stimulationHealth-related qualityKey eligibility criteriaRegulatory T cellsT cell dysfunctionCell effector functionsALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer.
Saji S, McArthur H, Ignatiadis M, Bailey A, El-Abed S, Brandao M, Metzger O, Lai C, Guillaume S, Fumagalli D, Agbor-tarh D, Seiller A, Xifro R, Honvault V, Viale G, DuFrane C, Barata T, Winer E, Gelber R, Piccart-Gebhart M. ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer. Journal Of Clinical Oncology 2021, 39: tps597-tps597. DOI: 10.1200/jco.2021.39.15_suppl.tps597.Peer-Reviewed Original ResearchTriple-negative breast cancerInvasive disease-free survivalEarly-stage triple-negative breast cancerPD-L1Breast cancerAdjuvant chemotherapyStage triple-negative breast cancerMetastatic triple-negative breast cancerPD-L1 negative tumorsF. Hoffmann-La Roche LtdBreast International GroupOperable stage IIRandomized phase 3Same chemotherapy regimenStandard adjuvant chemotherapyCentral pathology reviewDisease-free survivalPD-L1 statusPhase 3 studyPhase 3 trialType of surgeryNegative breast cancerQuality of lifeAtezolizumab 1200Weekly paclitaxelPembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial
Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J, investigators K. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. The Lancet Oncology 2021, 22: 499-511. PMID: 33676601, DOI: 10.1016/s1470-2045(20)30754-3.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerCombined positive scoreMedian overall survivalPD-L1 combined positive scoreTreatment-related adverse eventsPhase 3 trialChemotherapy groupOverall survivalPembrolizumab groupBreast cancerAdverse eventsPrimary endpointMetastatic diseaseEastern Cooperative Oncology Group performance statusPD-L1 tumor statusCommon grade 3Durable antitumour activityInvestigator-choice chemotherapyPrevious systemic treatmentSerious adverse eventsThird-line treatmentSubpopulation of patientsTreatment of patientsSingle-drug chemotherapyClinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
Keenan TE, Li T, Vallius T, Guerriero JL, Tayob N, Kochupurakkal B, Davis J, Pastorello R, Tahara RK, Anderson L, Conway J, He MX, Shannon E, Godin RE, Sorger PK, D'Andrea A, Overmoyer B, Winer EP, Mittendorf EA, Van Allen EM, Shapiro GI, Tolaney SM. Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: 983-991. PMID: 33257427, PMCID: PMC7887044, DOI: 10.1158/1078-0432.ccr-20-3089.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerObjective response rateTriple-negative breast cancerWEE1 inhibitor adavosertibPrior linesClinical benefitBreast cancerMedian progression-free survivalTreatment-related grade 3One-sided type I errorImmune-infiltrated tumorsPhase II studyProgression-free survivalT cell infiltrationImmune gene expressionPrior chemotherapyStable diseaseProtocol therapyII studyPartial responseAdverse eventsMedian ageClinical efficacyGrade 3Tumor biopsiesAtezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study
Emens LA, Molinero L, Loi S, Rugo HS, Schneeweiss A, Diéras V, Iwata H, Barrios CH, Nechaeva M, Nguyen-Duc A, Chui SY, Husain A, Winer EP, Adams S, Schmid P. Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study. Journal Of The National Cancer Institute 2021, 113: 1005-1016. PMID: 33523233, PMCID: PMC8328980, DOI: 10.1093/jnci/djab004.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerMetastatic triple-negative breast cancerProgression-free survivalPD-L1Tumor immune microenvironmentBreast cancerIntratumoral CD8Nab-paclitaxelClinical benefitImmune microenvironmentImmune cellsBRCA1/2 mutationsAdvanced triple-negative breast cancerStromal tumor-infiltrating lymphocytesNab-paclitaxel 100Immune checkpoint inhibitorsOverall survival benefitTumor-infiltrating lymphocytesMetastatic tumor tissueBRCA1/2 mutation statusCheckpoint inhibitorsOverall survivalSurvival benefitImmune biomarkersClinical activity
2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patients44O Pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-119 Asia-Pacific subpopulation
Im S, Cortes J, Lipatov O, Goncalves A, Lee K, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Zambelli S, Harbeck N, Andre F, Dent R, Lin J, Karantza V, Mejia J, Winer E. 44O Pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-119 Asia-Pacific subpopulation. Annals Of Oncology 2020, 31: s1258. DOI: 10.1016/j.annonc.2020.10.064.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTriple-negative breast cancerBreast cancerPembrolizumabChemotherapyCancer49MO IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer
Iwata H, Emens L, Adams S, Barrios C, Diéras V, Loi S, Rugo H, Schneeweiss A, Winer E, Patel S, Henschel V, Swat A, Kaul M, Molinero L, Chui S, Schmid P. 49MO IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Annals Of Oncology 2020, 31: s1261-s1262. DOI: 10.1016/j.annonc.2020.10.069.Peer-Reviewed Original ResearchNab-paclitaxelMetastatic triple-negative breast cancerPivotal phase III studiesTriple-negative breast cancerFinal OS analysisPhase III studyIII studyBreast cancerOS analysisAtezolizumabPlaceboCancerIMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer
Emens L, Adams S, Barrios C, Dieras V, Iwata H, Loi S, Rugo H, Schneeweiss A, Winer E, Patel S, Henschel V, Swat A, Kaul M, Molinero L, Chui S, Schmid P. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Annals Of Oncology 2020, 31: s1148. PMCID: PMC7506448, DOI: 10.1016/j.annonc.2020.08.2244.Peer-Reviewed Original ResearchNab-paclitaxelMetastatic triple-negative breast cancerPivotal phase III studiesTriple-negative breast cancerFinal OS analysisPhase III studyIII studyBreast cancerOS analysisAtezolizumabPlaceboCancer