Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study
The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this...
Gespeichert in:
| Veröffentlicht in: | The lancet oncology 2024-01, Vol.25 (1), p.46-61 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 61 |
|---|---|
| container_issue | 1 |
| container_start_page | 46 |
| container_title | The lancet oncology |
| container_volume | 25 |
| creator | Bamias, Aristotelis Davis, Ian D Galsky, Matthew D Arranz, José Á Kikuchi, Eiji Grande, Enrique Del Muro, Xavier Garcia Park, Se Hoon De Giorgi, Ugo Alekseev, Boris Mencinger, Marina Izumi, Kouji Schutz, Fabio A Puente, Javier Li, Jian-Ri Panni, Stefano Gumus, Mahmut Özgüroğlu, Mustafa Mariathasan, Sanjeev Poloz, Yekaterina Bene-Tchaleu, Fabiola Lee, Chooi Bernhard, Sandrine De Santis, Maria |
| description | The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this finding did not translate into significant overall survival benefit for group A versus group C at the final analysis, precluding formal statistical testing of outcomes with atezolizumab monotherapy (group B) versus group C. Here we report the final overall survival results for group B versus group C; this report is descriptive and should be considered exploratory due to the study's statistical design.
In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) who had locally advanced or metastatic urothelial cancer previously untreated in the metastatic setting and Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), using a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin score, and investigator's choice of platinum-based chemotherapy, to receive either atezolizumab plus platinum-based chemotherapy (group A), atezolizumab alone (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo in group A and group C; atezolizumab monotherapy in group B was open label. For groups B and C, atezolizumab (1200 mg) or placebo was administered intravenously every 3 weeks. Chemotherapy involved 21-day cycles of gemcitabine (1000 mg/m
body surface area on day 1 and day 8 of each cycle) plus the investigator's choice of carboplatin (area under the curve 4·5 mg/mL per min or 5 mg/mL per min) or cisplatin (70 mg/m
body surface area), administered intravenously. Co-primary endpoints were progression-free survival and overall survival in group A versus group C, and overall survival in group B versus group C, tested hierarchically, in the intention-to-treat (ITT) population, and then the populations with high PD-L1 tumour expression (immune cell [IC] expression score of IC2/3) if the results from group A versus group C were significant. Here, we report the co-primary endpoint of overall survival for group B versus group C in the ITT and IC2/3 populatio |
| doi_str_mv | 10.1016/S1470-2045(23)00539-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2902949004</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2919783154</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-82479e0bb3aecccafd07a57eedcff52daa6bf3fecd85777e4994bc0ef49a4c083</originalsourceid><addsrcrecordid>eNpdkc1u1DAUhSMEoqXwCCBLbKYSATt26ri7quKnUhELYB3d2NeMKycebCfS9Al5LJyZ0gUrXx1_51xbp6peM_qeUXbx4TsTktYNFe2m4eeUtlzV6kl1WmRRt6Lrnh7mI3JSvUjpjlImGW2fVye8KxmCs9Pqz1XG--Dd_TzCQMYwhbzFCLs9WTCmORG9xfFRcxOZpxwRMhrigwbv9wTMApMuQohkxAwpQ3aazHG1eQeeaIjaTWEEsrn5urhfITJOzy-JdVO5DWVTCSJpjotbigBF3SeXiI1hJEAiTCaMLqF5R3Qo-4P367zbQkLCScqz2b-snlnwCV89nGfVz08ff1x_qW-_fb65vrqtNecy110jpEI6DBxQaw3WUAmtRDTa2rYxABeD5Ra16VopJQqlxKApWqFAaNrxs2pzzN3F8HvGlPvyMo3ew4RhTn2jaKOEolQU9O1_6F2YY_ncSjElO87alWqPlI4hpYi230U3Qtz3jPZr1f2h6n7tsW94f6i6V8X35iF9HkY0j65_3fK_Ew-qsw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2919783154</pqid></control><display><type>article</type><title>Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Bamias, Aristotelis ; Davis, Ian D ; Galsky, Matthew D ; Arranz, José Á ; Kikuchi, Eiji ; Grande, Enrique ; Del Muro, Xavier Garcia ; Park, Se Hoon ; De Giorgi, Ugo ; Alekseev, Boris ; Mencinger, Marina ; Izumi, Kouji ; Schutz, Fabio A ; Puente, Javier ; Li, Jian-Ri ; Panni, Stefano ; Gumus, Mahmut ; Özgüroğlu, Mustafa ; Mariathasan, Sanjeev ; Poloz, Yekaterina ; Bene-Tchaleu, Fabiola ; Lee, Chooi ; Bernhard, Sandrine ; De Santis, Maria</creator><creatorcontrib>Bamias, Aristotelis ; Davis, Ian D ; Galsky, Matthew D ; Arranz, José Á ; Kikuchi, Eiji ; Grande, Enrique ; Del Muro, Xavier Garcia ; Park, Se Hoon ; De Giorgi, Ugo ; Alekseev, Boris ; Mencinger, Marina ; Izumi, Kouji ; Schutz, Fabio A ; Puente, Javier ; Li, Jian-Ri ; Panni, Stefano ; Gumus, Mahmut ; Özgüroğlu, Mustafa ; Mariathasan, Sanjeev ; Poloz, Yekaterina ; Bene-Tchaleu, Fabiola ; Lee, Chooi ; Bernhard, Sandrine ; De Santis, Maria</creatorcontrib><description>The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this finding did not translate into significant overall survival benefit for group A versus group C at the final analysis, precluding formal statistical testing of outcomes with atezolizumab monotherapy (group B) versus group C. Here we report the final overall survival results for group B versus group C; this report is descriptive and should be considered exploratory due to the study's statistical design.
In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) who had locally advanced or metastatic urothelial cancer previously untreated in the metastatic setting and Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), using a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin score, and investigator's choice of platinum-based chemotherapy, to receive either atezolizumab plus platinum-based chemotherapy (group A), atezolizumab alone (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo in group A and group C; atezolizumab monotherapy in group B was open label. For groups B and C, atezolizumab (1200 mg) or placebo was administered intravenously every 3 weeks. Chemotherapy involved 21-day cycles of gemcitabine (1000 mg/m
body surface area on day 1 and day 8 of each cycle) plus the investigator's choice of carboplatin (area under the curve 4·5 mg/mL per min or 5 mg/mL per min) or cisplatin (70 mg/m
body surface area), administered intravenously. Co-primary endpoints were progression-free survival and overall survival in group A versus group C, and overall survival in group B versus group C, tested hierarchically, in the intention-to-treat (ITT) population, and then the populations with high PD-L1 tumour expression (immune cell [IC] expression score of IC2/3) if the results from group A versus group C were significant. Here, we report the co-primary endpoint of overall survival for group B versus group C in the ITT and IC2/3 populations. The ITT population for this analysis comprised concurrently enrolled patients in groups B and C who were randomly assigned to treatment. For the safety analysis, all patients enrolled in group B and group C who received any study treatment were included. The trial is registered with ClinicalTrials.gov, NCT02807636, and is active but no longer recruiting.
Between July 15, 2016, and July 20, 2018, 1213 patients were enrolled and randomly assigned to treatment, of whom 362 patients were assigned to group B and 400 to group C, of whom 360 and 359, respectively, were enrolled concurrently (ITT population). 543 (76%) of 719 patients were male, 176 (24%) were female, and 534 (74%) were White. As of data cutoff (Aug 31, 2022), after a median follow-up of 13·4 months (IQR 6·2-30·8), median overall survival was 15·2 months (95% CI 13·1-17·7; 271 deaths) in group B and 13·3 months (11·9-15·6; 275 deaths) in group C (stratified hazard ratio 0·98 [95% CI 0·82-1·16]). The most common grade 3-4 treatment-related adverse events were anaemia (two [1%] in patients who received atezolizumab monotherapy vs 133 [34%] in those who received placebo plus chemotherapy), neutropenia (one [<1%] vs 115 [30%]), decreased neutrophil count (0 vs 95 [24%]), and decreased platelet count (one [<1%] vs 92 [24%]). Serious adverse events occurred in 163 (46%) patients versus 196 (50%). Treatment-related deaths occurred in three (1%; n=1 each, pneumonia, interstitial lung disease, large intestinal obstruction) patients who received atezolizumab monotherapy and four (1%; n=1 each, diarrhoea, febrile neutropenia, unexplained death, toxic hepatitis) who received placebo plus chemotherapy.
The final analysis from IMvigor130 did not show a significant improvement in overall survival with first-line atezolizumab monotherapy compared with platinum-based chemotherapy in the intention-to-treat population. The safety profile of atezolizumab monotherapy remained acceptable after extended follow-up, with no new safety signals.
F Hoffmann-La Roche.</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(23)00539-9</identifier><identifier>PMID: 38101431</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Adolescent ; Adult ; Adverse events ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; B7-H1 Antigen ; Cancer ; Carboplatin ; Carcinoma, Transitional Cell - drug therapy ; Chemotherapy ; Cisplatin ; Diarrhea ; Female ; Gemcitabine ; Hepatitis ; Humans ; Immunotherapy ; Leukocytes (neutrophilic) ; Lung diseases ; Male ; Metastases ; Metastasis ; Monoclonal antibodies ; Neutropenia ; Oncology ; Patients ; PD-L1 protein ; Placebos ; Platinum ; Safety ; Standard of care ; Statistics ; Surface area ; Survival Analysis ; Targeted cancer therapy ; Tumors ; Urinary Bladder Neoplasms ; Urological cancer ; Urothelial cancer ; Urothelial carcinoma</subject><ispartof>The lancet oncology, 2024-01, Vol.25 (1), p.46-61</ispartof><rights>Copyright © 2024 Elsevier Ltd. All rights reserved.</rights><rights>2024. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-82479e0bb3aecccafd07a57eedcff52daa6bf3fecd85777e4994bc0ef49a4c083</citedby><cites>FETCH-LOGICAL-c337t-82479e0bb3aecccafd07a57eedcff52daa6bf3fecd85777e4994bc0ef49a4c083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38101431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bamias, Aristotelis</creatorcontrib><creatorcontrib>Davis, Ian D</creatorcontrib><creatorcontrib>Galsky, Matthew D</creatorcontrib><creatorcontrib>Arranz, José Á</creatorcontrib><creatorcontrib>Kikuchi, Eiji</creatorcontrib><creatorcontrib>Grande, Enrique</creatorcontrib><creatorcontrib>Del Muro, Xavier Garcia</creatorcontrib><creatorcontrib>Park, Se Hoon</creatorcontrib><creatorcontrib>De Giorgi, Ugo</creatorcontrib><creatorcontrib>Alekseev, Boris</creatorcontrib><creatorcontrib>Mencinger, Marina</creatorcontrib><creatorcontrib>Izumi, Kouji</creatorcontrib><creatorcontrib>Schutz, Fabio A</creatorcontrib><creatorcontrib>Puente, Javier</creatorcontrib><creatorcontrib>Li, Jian-Ri</creatorcontrib><creatorcontrib>Panni, Stefano</creatorcontrib><creatorcontrib>Gumus, Mahmut</creatorcontrib><creatorcontrib>Özgüroğlu, Mustafa</creatorcontrib><creatorcontrib>Mariathasan, Sanjeev</creatorcontrib><creatorcontrib>Poloz, Yekaterina</creatorcontrib><creatorcontrib>Bene-Tchaleu, Fabiola</creatorcontrib><creatorcontrib>Lee, Chooi</creatorcontrib><creatorcontrib>Bernhard, Sandrine</creatorcontrib><creatorcontrib>De Santis, Maria</creatorcontrib><title>Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this finding did not translate into significant overall survival benefit for group A versus group C at the final analysis, precluding formal statistical testing of outcomes with atezolizumab monotherapy (group B) versus group C. Here we report the final overall survival results for group B versus group C; this report is descriptive and should be considered exploratory due to the study's statistical design.
In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) who had locally advanced or metastatic urothelial cancer previously untreated in the metastatic setting and Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), using a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin score, and investigator's choice of platinum-based chemotherapy, to receive either atezolizumab plus platinum-based chemotherapy (group A), atezolizumab alone (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo in group A and group C; atezolizumab monotherapy in group B was open label. For groups B and C, atezolizumab (1200 mg) or placebo was administered intravenously every 3 weeks. Chemotherapy involved 21-day cycles of gemcitabine (1000 mg/m
body surface area on day 1 and day 8 of each cycle) plus the investigator's choice of carboplatin (area under the curve 4·5 mg/mL per min or 5 mg/mL per min) or cisplatin (70 mg/m
body surface area), administered intravenously. Co-primary endpoints were progression-free survival and overall survival in group A versus group C, and overall survival in group B versus group C, tested hierarchically, in the intention-to-treat (ITT) population, and then the populations with high PD-L1 tumour expression (immune cell [IC] expression score of IC2/3) if the results from group A versus group C were significant. Here, we report the co-primary endpoint of overall survival for group B versus group C in the ITT and IC2/3 populations. The ITT population for this analysis comprised concurrently enrolled patients in groups B and C who were randomly assigned to treatment. For the safety analysis, all patients enrolled in group B and group C who received any study treatment were included. The trial is registered with ClinicalTrials.gov, NCT02807636, and is active but no longer recruiting.
Between July 15, 2016, and July 20, 2018, 1213 patients were enrolled and randomly assigned to treatment, of whom 362 patients were assigned to group B and 400 to group C, of whom 360 and 359, respectively, were enrolled concurrently (ITT population). 543 (76%) of 719 patients were male, 176 (24%) were female, and 534 (74%) were White. As of data cutoff (Aug 31, 2022), after a median follow-up of 13·4 months (IQR 6·2-30·8), median overall survival was 15·2 months (95% CI 13·1-17·7; 271 deaths) in group B and 13·3 months (11·9-15·6; 275 deaths) in group C (stratified hazard ratio 0·98 [95% CI 0·82-1·16]). The most common grade 3-4 treatment-related adverse events were anaemia (two [1%] in patients who received atezolizumab monotherapy vs 133 [34%] in those who received placebo plus chemotherapy), neutropenia (one [<1%] vs 115 [30%]), decreased neutrophil count (0 vs 95 [24%]), and decreased platelet count (one [<1%] vs 92 [24%]). Serious adverse events occurred in 163 (46%) patients versus 196 (50%). Treatment-related deaths occurred in three (1%; n=1 each, pneumonia, interstitial lung disease, large intestinal obstruction) patients who received atezolizumab monotherapy and four (1%; n=1 each, diarrhoea, febrile neutropenia, unexplained death, toxic hepatitis) who received placebo plus chemotherapy.
The final analysis from IMvigor130 did not show a significant improvement in overall survival with first-line atezolizumab monotherapy compared with platinum-based chemotherapy in the intention-to-treat population. The safety profile of atezolizumab monotherapy remained acceptable after extended follow-up, with no new safety signals.
F Hoffmann-La Roche.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Adverse events</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>B7-H1 Antigen</subject><subject>Cancer</subject><subject>Carboplatin</subject><subject>Carcinoma, Transitional Cell - drug therapy</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Diarrhea</subject><subject>Female</subject><subject>Gemcitabine</subject><subject>Hepatitis</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lung diseases</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Monoclonal antibodies</subject><subject>Neutropenia</subject><subject>Oncology</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Placebos</subject><subject>Platinum</subject><subject>Safety</subject><subject>Standard of care</subject><subject>Statistics</subject><subject>Surface area</subject><subject>Survival Analysis</subject><subject>Targeted cancer therapy</subject><subject>Tumors</subject><subject>Urinary Bladder Neoplasms</subject><subject>Urological cancer</subject><subject>Urothelial cancer</subject><subject>Urothelial carcinoma</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkc1u1DAUhSMEoqXwCCBLbKYSATt26ri7quKnUhELYB3d2NeMKycebCfS9Al5LJyZ0gUrXx1_51xbp6peM_qeUXbx4TsTktYNFe2m4eeUtlzV6kl1WmRRt6Lrnh7mI3JSvUjpjlImGW2fVye8KxmCs9Pqz1XG--Dd_TzCQMYwhbzFCLs9WTCmORG9xfFRcxOZpxwRMhrigwbv9wTMApMuQohkxAwpQ3aazHG1eQeeaIjaTWEEsrn5urhfITJOzy-JdVO5DWVTCSJpjotbigBF3SeXiI1hJEAiTCaMLqF5R3Qo-4P367zbQkLCScqz2b-snlnwCV89nGfVz08ff1x_qW-_fb65vrqtNecy110jpEI6DBxQaw3WUAmtRDTa2rYxABeD5Ra16VopJQqlxKApWqFAaNrxs2pzzN3F8HvGlPvyMo3ew4RhTn2jaKOEolQU9O1_6F2YY_ncSjElO87alWqPlI4hpYi230U3Qtz3jPZr1f2h6n7tsW94f6i6V8X35iF9HkY0j65_3fK_Ew-qsw</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Bamias, Aristotelis</creator><creator>Davis, Ian D</creator><creator>Galsky, Matthew D</creator><creator>Arranz, José Á</creator><creator>Kikuchi, Eiji</creator><creator>Grande, Enrique</creator><creator>Del Muro, Xavier Garcia</creator><creator>Park, Se Hoon</creator><creator>De Giorgi, Ugo</creator><creator>Alekseev, Boris</creator><creator>Mencinger, Marina</creator><creator>Izumi, Kouji</creator><creator>Schutz, Fabio A</creator><creator>Puente, Javier</creator><creator>Li, Jian-Ri</creator><creator>Panni, Stefano</creator><creator>Gumus, Mahmut</creator><creator>Özgüroğlu, Mustafa</creator><creator>Mariathasan, Sanjeev</creator><creator>Poloz, Yekaterina</creator><creator>Bene-Tchaleu, Fabiola</creator><creator>Lee, Chooi</creator><creator>Bernhard, Sandrine</creator><creator>De Santis, Maria</creator><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>202401</creationdate><title>Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study</title><author>Bamias, Aristotelis ; Davis, Ian D ; Galsky, Matthew D ; Arranz, José Á ; Kikuchi, Eiji ; Grande, Enrique ; Del Muro, Xavier Garcia ; Park, Se Hoon ; De Giorgi, Ugo ; Alekseev, Boris ; Mencinger, Marina ; Izumi, Kouji ; Schutz, Fabio A ; Puente, Javier ; Li, Jian-Ri ; Panni, Stefano ; Gumus, Mahmut ; Özgüroğlu, Mustafa ; Mariathasan, Sanjeev ; Poloz, Yekaterina ; Bene-Tchaleu, Fabiola ; Lee, Chooi ; Bernhard, Sandrine ; De Santis, Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-82479e0bb3aecccafd07a57eedcff52daa6bf3fecd85777e4994bc0ef49a4c083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adverse events</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>B7-H1 Antigen</topic><topic>Cancer</topic><topic>Carboplatin</topic><topic>Carcinoma, Transitional Cell - drug therapy</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Diarrhea</topic><topic>Female</topic><topic>Gemcitabine</topic><topic>Hepatitis</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lung diseases</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Monoclonal antibodies</topic><topic>Neutropenia</topic><topic>Oncology</topic><topic>Patients</topic><topic>PD-L1 protein</topic><topic>Placebos</topic><topic>Platinum</topic><topic>Safety</topic><topic>Standard of care</topic><topic>Statistics</topic><topic>Surface area</topic><topic>Survival Analysis</topic><topic>Targeted cancer therapy</topic><topic>Tumors</topic><topic>Urinary Bladder Neoplasms</topic><topic>Urological cancer</topic><topic>Urothelial cancer</topic><topic>Urothelial carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bamias, Aristotelis</creatorcontrib><creatorcontrib>Davis, Ian D</creatorcontrib><creatorcontrib>Galsky, Matthew D</creatorcontrib><creatorcontrib>Arranz, José Á</creatorcontrib><creatorcontrib>Kikuchi, Eiji</creatorcontrib><creatorcontrib>Grande, Enrique</creatorcontrib><creatorcontrib>Del Muro, Xavier Garcia</creatorcontrib><creatorcontrib>Park, Se Hoon</creatorcontrib><creatorcontrib>De Giorgi, Ugo</creatorcontrib><creatorcontrib>Alekseev, Boris</creatorcontrib><creatorcontrib>Mencinger, Marina</creatorcontrib><creatorcontrib>Izumi, Kouji</creatorcontrib><creatorcontrib>Schutz, Fabio A</creatorcontrib><creatorcontrib>Puente, Javier</creatorcontrib><creatorcontrib>Li, Jian-Ri</creatorcontrib><creatorcontrib>Panni, Stefano</creatorcontrib><creatorcontrib>Gumus, Mahmut</creatorcontrib><creatorcontrib>Özgüroğlu, Mustafa</creatorcontrib><creatorcontrib>Mariathasan, Sanjeev</creatorcontrib><creatorcontrib>Poloz, Yekaterina</creatorcontrib><creatorcontrib>Bene-Tchaleu, Fabiola</creatorcontrib><creatorcontrib>Lee, Chooi</creatorcontrib><creatorcontrib>Bernhard, Sandrine</creatorcontrib><creatorcontrib>De Santis, Maria</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bamias, Aristotelis</au><au>Davis, Ian D</au><au>Galsky, Matthew D</au><au>Arranz, José Á</au><au>Kikuchi, Eiji</au><au>Grande, Enrique</au><au>Del Muro, Xavier Garcia</au><au>Park, Se Hoon</au><au>De Giorgi, Ugo</au><au>Alekseev, Boris</au><au>Mencinger, Marina</au><au>Izumi, Kouji</au><au>Schutz, Fabio A</au><au>Puente, Javier</au><au>Li, Jian-Ri</au><au>Panni, Stefano</au><au>Gumus, Mahmut</au><au>Özgüroğlu, Mustafa</au><au>Mariathasan, Sanjeev</au><au>Poloz, Yekaterina</au><au>Bene-Tchaleu, Fabiola</au><au>Lee, Chooi</au><au>Bernhard, Sandrine</au><au>De Santis, Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2024-01</date><risdate>2024</risdate><volume>25</volume><issue>1</issue><spage>46</spage><epage>61</epage><pages>46-61</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><abstract>The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this finding did not translate into significant overall survival benefit for group A versus group C at the final analysis, precluding formal statistical testing of outcomes with atezolizumab monotherapy (group B) versus group C. Here we report the final overall survival results for group B versus group C; this report is descriptive and should be considered exploratory due to the study's statistical design.
In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) who had locally advanced or metastatic urothelial cancer previously untreated in the metastatic setting and Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), using a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin score, and investigator's choice of platinum-based chemotherapy, to receive either atezolizumab plus platinum-based chemotherapy (group A), atezolizumab alone (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo in group A and group C; atezolizumab monotherapy in group B was open label. For groups B and C, atezolizumab (1200 mg) or placebo was administered intravenously every 3 weeks. Chemotherapy involved 21-day cycles of gemcitabine (1000 mg/m
body surface area on day 1 and day 8 of each cycle) plus the investigator's choice of carboplatin (area under the curve 4·5 mg/mL per min or 5 mg/mL per min) or cisplatin (70 mg/m
body surface area), administered intravenously. Co-primary endpoints were progression-free survival and overall survival in group A versus group C, and overall survival in group B versus group C, tested hierarchically, in the intention-to-treat (ITT) population, and then the populations with high PD-L1 tumour expression (immune cell [IC] expression score of IC2/3) if the results from group A versus group C were significant. Here, we report the co-primary endpoint of overall survival for group B versus group C in the ITT and IC2/3 populations. The ITT population for this analysis comprised concurrently enrolled patients in groups B and C who were randomly assigned to treatment. For the safety analysis, all patients enrolled in group B and group C who received any study treatment were included. The trial is registered with ClinicalTrials.gov, NCT02807636, and is active but no longer recruiting.
Between July 15, 2016, and July 20, 2018, 1213 patients were enrolled and randomly assigned to treatment, of whom 362 patients were assigned to group B and 400 to group C, of whom 360 and 359, respectively, were enrolled concurrently (ITT population). 543 (76%) of 719 patients were male, 176 (24%) were female, and 534 (74%) were White. As of data cutoff (Aug 31, 2022), after a median follow-up of 13·4 months (IQR 6·2-30·8), median overall survival was 15·2 months (95% CI 13·1-17·7; 271 deaths) in group B and 13·3 months (11·9-15·6; 275 deaths) in group C (stratified hazard ratio 0·98 [95% CI 0·82-1·16]). The most common grade 3-4 treatment-related adverse events were anaemia (two [1%] in patients who received atezolizumab monotherapy vs 133 [34%] in those who received placebo plus chemotherapy), neutropenia (one [<1%] vs 115 [30%]), decreased neutrophil count (0 vs 95 [24%]), and decreased platelet count (one [<1%] vs 92 [24%]). Serious adverse events occurred in 163 (46%) patients versus 196 (50%). Treatment-related deaths occurred in three (1%; n=1 each, pneumonia, interstitial lung disease, large intestinal obstruction) patients who received atezolizumab monotherapy and four (1%; n=1 each, diarrhoea, febrile neutropenia, unexplained death, toxic hepatitis) who received placebo plus chemotherapy.
The final analysis from IMvigor130 did not show a significant improvement in overall survival with first-line atezolizumab monotherapy compared with platinum-based chemotherapy in the intention-to-treat population. The safety profile of atezolizumab monotherapy remained acceptable after extended follow-up, with no new safety signals.
F Hoffmann-La Roche.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>38101431</pmid><doi>10.1016/S1470-2045(23)00539-9</doi><tpages>16</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-2045 |
| ispartof | The lancet oncology, 2024-01, Vol.25 (1), p.46-61 |
| issn | 1470-2045 1474-5488 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2902949004 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescent Adult Adverse events Antineoplastic Combined Chemotherapy Protocols - adverse effects B7-H1 Antigen Cancer Carboplatin Carcinoma, Transitional Cell - drug therapy Chemotherapy Cisplatin Diarrhea Female Gemcitabine Hepatitis Humans Immunotherapy Leukocytes (neutrophilic) Lung diseases Male Metastases Metastasis Monoclonal antibodies Neutropenia Oncology Patients PD-L1 protein Placebos Platinum Safety Standard of care Statistics Surface area Survival Analysis Targeted cancer therapy Tumors Urinary Bladder Neoplasms Urological cancer Urothelial cancer Urothelial carcinoma |
| title | Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T22%3A29%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Atezolizumab%20monotherapy%20versus%20chemotherapy%20in%20untreated%20locally%20advanced%20or%20metastatic%20urothelial%20carcinoma%20(IMvigor130):%20final%20overall%20survival%20analysis%20from%20a%20randomised,%20controlled,%20phase%203%20study&rft.jtitle=The%20lancet%20oncology&rft.au=Bamias,%20Aristotelis&rft.date=2024-01&rft.volume=25&rft.issue=1&rft.spage=46&rft.epage=61&rft.pages=46-61&rft.issn=1470-2045&rft.eissn=1474-5488&rft_id=info:doi/10.1016/S1470-2045(23)00539-9&rft_dat=%3Cproquest_cross%3E2919783154%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2919783154&rft_id=info:pmid/38101431&rfr_iscdi=true |