First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial
In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' f...
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| Veröffentlicht in: | Journal of thoracic oncology 2022-02, Vol.17 (2), p.289-308 |
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| creator | Paz-Ares, Luis G. Ramalingam, Suresh S. Ciuleanu, Tudor-Eliade Lee, Jong-Seok Urban, Laszlo Caro, Reyes Bernabe Park, Keunchil Sakai, Hiroshi Ohe, Yuichiro Nishio, Makoto Audigier-Valette, Clarisse Burgers, Jacobus A. Pluzanski, Adam Sangha, Randeep Gallardo, Carlos Takeda, Masayuki Linardou, Helena Lupinacci, Lorena Lee, Ki Hyeong Caserta, Claudia Provencio, Mariano Carcereny, Enric Otterson, Gregory A. Schenker, Michael Zurawski, Bogdan Alexandru, Aurelia Vergnenegre, Alain Raimbourg, Judith Feeney, Kynan Kim, Sang-We Borghaei, Hossein O'Byrne, Kenneth John Hellmann, Matthew D. Memaj, Arteid Nathan, Faith Ellen Bushong, Judith Tran, Phuong Brahmer, Julie R. Reck, Martin |
| description | In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up.
Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 |
| doi_str_mv | 10.1016/j.jtho.2021.09.010 |
| format | Article |
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Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Efficacy included OS and other measures. Safety included timing and management of immune-mediated adverse events (AEs). A post hoc analysis evaluated efficacy in patients who discontinued nivolumab plus ipilimumab due to treatment-related AEs (TRAEs).
After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65–0.90) and PD-L1 less than 1% (0.64; 0.51–0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Safety was consistent with previous reports. The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash; most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population.
At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.</description><identifier>ISSN: 1556-0864</identifier><identifier>EISSN: 1556-1380</identifier><identifier>DOI: 10.1016/j.jtho.2021.09.010</identifier><identifier>PMID: 34648948</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; CTLA-4 ; First-line ; Humans ; Immunotherapy ; Ipilimumab - adverse effects ; Lung Neoplasms - pathology ; Metastatic non–small cell lung cancer ; Neoplasm Recurrence, Local - drug therapy ; Nivolumab - adverse effects ; PD-1 checkpoint inhibitor</subject><ispartof>Journal of thoracic oncology, 2022-02, Vol.17 (2), p.289-308</ispartof><rights>2021 International Association for the Study of Lung Cancer</rights><rights>Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-7aaa40c3df895385de48e5cc564b36b94079fff4bf26f12dc7e54a77879b47473</citedby><cites>FETCH-LOGICAL-c515t-7aaa40c3df895385de48e5cc564b36b94079fff4bf26f12dc7e54a77879b47473</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/34648948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paz-Ares, Luis G.</creatorcontrib><creatorcontrib>Ramalingam, Suresh S.</creatorcontrib><creatorcontrib>Ciuleanu, Tudor-Eliade</creatorcontrib><creatorcontrib>Lee, Jong-Seok</creatorcontrib><creatorcontrib>Urban, Laszlo</creatorcontrib><creatorcontrib>Caro, Reyes Bernabe</creatorcontrib><creatorcontrib>Park, Keunchil</creatorcontrib><creatorcontrib>Sakai, Hiroshi</creatorcontrib><creatorcontrib>Ohe, Yuichiro</creatorcontrib><creatorcontrib>Nishio, Makoto</creatorcontrib><creatorcontrib>Audigier-Valette, Clarisse</creatorcontrib><creatorcontrib>Burgers, Jacobus A.</creatorcontrib><creatorcontrib>Pluzanski, Adam</creatorcontrib><creatorcontrib>Sangha, Randeep</creatorcontrib><creatorcontrib>Gallardo, Carlos</creatorcontrib><creatorcontrib>Takeda, Masayuki</creatorcontrib><creatorcontrib>Linardou, Helena</creatorcontrib><creatorcontrib>Lupinacci, Lorena</creatorcontrib><creatorcontrib>Lee, Ki Hyeong</creatorcontrib><creatorcontrib>Caserta, Claudia</creatorcontrib><creatorcontrib>Provencio, Mariano</creatorcontrib><creatorcontrib>Carcereny, Enric</creatorcontrib><creatorcontrib>Otterson, Gregory A.</creatorcontrib><creatorcontrib>Schenker, Michael</creatorcontrib><creatorcontrib>Zurawski, Bogdan</creatorcontrib><creatorcontrib>Alexandru, Aurelia</creatorcontrib><creatorcontrib>Vergnenegre, Alain</creatorcontrib><creatorcontrib>Raimbourg, Judith</creatorcontrib><creatorcontrib>Feeney, Kynan</creatorcontrib><creatorcontrib>Kim, Sang-We</creatorcontrib><creatorcontrib>Borghaei, Hossein</creatorcontrib><creatorcontrib>O'Byrne, Kenneth John</creatorcontrib><creatorcontrib>Hellmann, Matthew D.</creatorcontrib><creatorcontrib>Memaj, Arteid</creatorcontrib><creatorcontrib>Nathan, Faith Ellen</creatorcontrib><creatorcontrib>Bushong, Judith</creatorcontrib><creatorcontrib>Tran, Phuong</creatorcontrib><creatorcontrib>Brahmer, Julie R.</creatorcontrib><creatorcontrib>Reck, Martin</creatorcontrib><title>First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial</title><title>Journal of thoracic oncology</title><addtitle>J Thorac Oncol</addtitle><description>In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up.
Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Efficacy included OS and other measures. Safety included timing and management of immune-mediated adverse events (AEs). A post hoc analysis evaluated efficacy in patients who discontinued nivolumab plus ipilimumab due to treatment-related AEs (TRAEs).
After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65–0.90) and PD-L1 less than 1% (0.64; 0.51–0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Safety was consistent with previous reports. The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash; most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population.
At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.</description><subject>Adult</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>CTLA-4</subject><subject>First-line</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Ipilimumab - adverse effects</subject><subject>Lung Neoplasms - pathology</subject><subject>Metastatic non–small cell lung cancer</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Nivolumab - adverse effects</subject><subject>PD-1 checkpoint inhibitor</subject><issn>1556-0864</issn><issn>1556-1380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUGP0zAQhS0EYpeFP8AB-chhE2zHjh3EZRVRWClsK1gOnCzHnqguSdy1k0rwF_jTpLRw5DQz0ntPmvch9JKSnBJavtnlu2kbckYYzUmVE0oeoUsqRJnRQpHH552okl-gZyntCOGCcPUUXRS85Kri6hL9WvmYpqzxI-A7fwj9PJgWb_o54du97_3w5_YjvnEHM1pw-O5L3dRvMc--gYl4PU82DJDwKoYBT1vAn83owuB_grvG6z2MWWNa6K_xZmsS4ALXW7DfP5kJMGMSb0ycMMX30Zv-OXrSmT7Bi_O8Ql9X7-_rj1mz_nBb3zSZFVRMmTTGcGIL16lKFEo44AqEtaLkbVG2FSey6rqOtx0rO8qclSC4kVLJquWSy-IKvT7l7mN4mCFNevDJQt-bEcKcNBOKKVoxKhYpO0ltDClF6PQ--sHEH5oSfYSgd_oIQR8haFLpBcJienXOn9sB3D_L39YXwbuTAJYvDx6iTtbDsV0fwU7aBf-__N_0M5ZX</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Paz-Ares, Luis G.</creator><creator>Ramalingam, Suresh S.</creator><creator>Ciuleanu, Tudor-Eliade</creator><creator>Lee, Jong-Seok</creator><creator>Urban, Laszlo</creator><creator>Caro, Reyes Bernabe</creator><creator>Park, Keunchil</creator><creator>Sakai, Hiroshi</creator><creator>Ohe, Yuichiro</creator><creator>Nishio, Makoto</creator><creator>Audigier-Valette, Clarisse</creator><creator>Burgers, Jacobus A.</creator><creator>Pluzanski, Adam</creator><creator>Sangha, Randeep</creator><creator>Gallardo, Carlos</creator><creator>Takeda, Masayuki</creator><creator>Linardou, Helena</creator><creator>Lupinacci, Lorena</creator><creator>Lee, Ki Hyeong</creator><creator>Caserta, Claudia</creator><creator>Provencio, Mariano</creator><creator>Carcereny, Enric</creator><creator>Otterson, Gregory A.</creator><creator>Schenker, Michael</creator><creator>Zurawski, Bogdan</creator><creator>Alexandru, Aurelia</creator><creator>Vergnenegre, Alain</creator><creator>Raimbourg, Judith</creator><creator>Feeney, Kynan</creator><creator>Kim, Sang-We</creator><creator>Borghaei, Hossein</creator><creator>O'Byrne, Kenneth John</creator><creator>Hellmann, Matthew D.</creator><creator>Memaj, Arteid</creator><creator>Nathan, Faith Ellen</creator><creator>Bushong, Judith</creator><creator>Tran, Phuong</creator><creator>Brahmer, Julie R.</creator><creator>Reck, Martin</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope></search><sort><creationdate>202202</creationdate><title>First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial</title><author>Paz-Ares, Luis G. ; Ramalingam, Suresh S. ; Ciuleanu, Tudor-Eliade ; Lee, Jong-Seok ; Urban, Laszlo ; Caro, Reyes Bernabe ; Park, Keunchil ; Sakai, Hiroshi ; Ohe, Yuichiro ; Nishio, Makoto ; Audigier-Valette, Clarisse ; Burgers, Jacobus A. ; Pluzanski, Adam ; Sangha, Randeep ; Gallardo, Carlos ; Takeda, Masayuki ; Linardou, Helena ; Lupinacci, Lorena ; Lee, Ki Hyeong ; Caserta, Claudia ; Provencio, Mariano ; Carcereny, Enric ; Otterson, Gregory A. ; Schenker, Michael ; Zurawski, Bogdan ; Alexandru, Aurelia ; Vergnenegre, Alain ; Raimbourg, Judith ; Feeney, Kynan ; Kim, Sang-We ; Borghaei, Hossein ; O'Byrne, Kenneth John ; Hellmann, Matthew D. ; Memaj, Arteid ; Nathan, Faith Ellen ; Bushong, Judith ; Tran, Phuong ; Brahmer, Julie R. ; Reck, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-7aaa40c3df895385de48e5cc564b36b94079fff4bf26f12dc7e54a77879b47473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Antineoplastic Combined Chemotherapy Protocols - 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Academic</collection><jtitle>Journal of thoracic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paz-Ares, Luis G.</au><au>Ramalingam, Suresh S.</au><au>Ciuleanu, Tudor-Eliade</au><au>Lee, Jong-Seok</au><au>Urban, Laszlo</au><au>Caro, Reyes Bernabe</au><au>Park, Keunchil</au><au>Sakai, Hiroshi</au><au>Ohe, Yuichiro</au><au>Nishio, Makoto</au><au>Audigier-Valette, Clarisse</au><au>Burgers, Jacobus A.</au><au>Pluzanski, Adam</au><au>Sangha, Randeep</au><au>Gallardo, Carlos</au><au>Takeda, Masayuki</au><au>Linardou, Helena</au><au>Lupinacci, Lorena</au><au>Lee, Ki Hyeong</au><au>Caserta, Claudia</au><au>Provencio, Mariano</au><au>Carcereny, Enric</au><au>Otterson, Gregory A.</au><au>Schenker, Michael</au><au>Zurawski, Bogdan</au><au>Alexandru, Aurelia</au><au>Vergnenegre, Alain</au><au>Raimbourg, Judith</au><au>Feeney, Kynan</au><au>Kim, Sang-We</au><au>Borghaei, Hossein</au><au>O'Byrne, Kenneth John</au><au>Hellmann, Matthew D.</au><au>Memaj, Arteid</au><au>Nathan, Faith Ellen</au><au>Bushong, Judith</au><au>Tran, Phuong</au><au>Brahmer, Julie R.</au><au>Reck, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial</atitle><jtitle>Journal of thoracic oncology</jtitle><addtitle>J Thorac Oncol</addtitle><date>2022-02</date><risdate>2022</risdate><volume>17</volume><issue>2</issue><spage>289</spage><epage>308</epage><pages>289-308</pages><issn>1556-0864</issn><eissn>1556-1380</eissn><abstract>In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up.
Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Efficacy included OS and other measures. Safety included timing and management of immune-mediated adverse events (AEs). A post hoc analysis evaluated efficacy in patients who discontinued nivolumab plus ipilimumab due to treatment-related AEs (TRAEs).
After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65–0.90) and PD-L1 less than 1% (0.64; 0.51–0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Safety was consistent with previous reports. The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash; most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population.
At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>34648948</pmid><doi>10.1016/j.jtho.2021.09.010</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1556-0864 |
| ispartof | Journal of thoracic oncology, 2022-02, Vol.17 (2), p.289-308 |
| issn | 1556-0864 1556-1380 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2582819215 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Antineoplastic Combined Chemotherapy Protocols - adverse effects CTLA-4 First-line Humans Immunotherapy Ipilimumab - adverse effects Lung Neoplasms - pathology Metastatic non–small cell lung cancer Neoplasm Recurrence, Local - drug therapy Nivolumab - adverse effects PD-1 checkpoint inhibitor |
| title | First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T23%3A49%3A35IST&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=First-Line%20Nivolumab%20Plus%20Ipilimumab%20in%20Advanced%20NSCLC:%204-Year%20Outcomes%20From%20the%20Randomized,%20Open-Label,%20Phase%203%20CheckMate%20227%20Part%201%20Trial&rft.jtitle=Journal%20of%20thoracic%20oncology&rft.au=Paz-Ares,%20Luis%20G.&rft.date=2022-02&rft.volume=17&rft.issue=2&rft.spage=289&rft.epage=308&rft.pages=289-308&rft.issn=1556-0864&rft.eissn=1556-1380&rft_id=info:doi/10.1016/j.jtho.2021.09.010&rft_dat=%3Cproquest_cross%3E2582819215%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=2582819215&rft_id=info:pmid/34648948&rft_els_id=S155608642103207X&rfr_iscdi=true |