{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:32:33Z","timestamp":1780504353923,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Few treatment options are available for patients with epidermal growth factor receptor (EGFR) mutation\u2010positive metastatic non\u2010squamous non\u2010small cell lung cancer (NSCLC) who failed treatment with EGFR\u2010tyrosine kinase inhibitors (EGFR\u2010TKIs). We aimed to assess the efficacy and safety of atezolizumab plus bevacizumab in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single\u2010arm, Simon's minimax two\u2010stage adapted phase II study. Patients received atezolizumab 1200\u2009mg plus bevacizumab 15\u2009mg\/kg once every 3\u2009weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included duration of response (DOR), time to response (TTR), progression\u2010free survival (PFS), overall survival (OS), and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 14 August 2020 and 18 January 2021, 23 patients from seven sites in China were enrolled; all received study treatment. Twenty\u2010two patients were evaluable for ORR. At data cut\u2010off, median follow\u2010up was 16.4\u2009months. The confirmed ORR was 18.2% (4\/22) per RECIST v1.1. The number of responders did not cross the predefined threshold (&gt;\u20096 patients) for stage II enrollment. For the four responding patients, the median TTR and DOR were 1.4 and 6.4\u2009months, respectively. Median PFS and OS were 2.8 and 14.1\u2009months, respectively. Atezolizumab plus bevacizumab had acceptable tolerability without any new safety signals identified. All patients experienced at least one treatment\u2010emergent adverse event (TEAE); four patients experienced serious TEAEs and one patient died of an unknown cause.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The chemotherapy\u2010free atezolizumab plus bevacizumab regimen had limited efficacy but an acceptable safety profile in this exploratory study. Although current data suggest that chemotherapy may still be important for patients who failed EGFR\u2010TKIs, more treatment regimens with lower toxicity and higher efficacy for these patients, such as antibody\u2013drug conjugates and bispecific antibodies, need to be explored in the future.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT04426825\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71469","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T13:14:21Z","timestamp":1765631661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Atezolizumab Plus Bevacizumab in Patients With Advanced\n                    <scp>NSCLC<\/scp>\n                    Who Received Pretreatment With\n                    <scp>EGFR<\/scp>\n                    \u2010\n                    <scp>TKIs<\/scp>\n                    (\n                    <scp>ML41256<\/scp>\n                    ): A Multicenter, Prospective, Single\u2010Arm, Phase 2 Trial"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-8246","authenticated-orcid":false,"given":"Wenfeng","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-3686","authenticated-orcid":false,"given":"Jian","family":"Fang","sequence":"additional","affiliation":[{"name":"Second Department of Thoracic Oncology Beijing Cancer Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-3228","authenticated-orcid":false,"given":"Panwen","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital Sichuan University  Chengdu China"},{"name":"Lung Cancer Center\/Lung Cancer Institute, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1755-0175","authenticated-orcid":false,"given":"Yun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Zhejiang Cancer Hospital  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qitao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology Guangxi Medical University Affiliated Tumor Hospital  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cancer Precision Medical Center, The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhehai","family":"Wang","sequence":"additional","affiliation":[{"name":"Respiratory Medical Oncology Ward II Shandong Cancer Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Affairs Shanghai Roche Pharmaceuticals Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Shi","sequence":"additional","affiliation":[{"name":"Medical Affairs Shanghai Roche Pharmaceuticals Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.7293"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11111102"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12587"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030629"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15020504"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2017.11.001"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.635007"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2023.2170879"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.9110"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.01.014"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2021.07.004"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(22)00382\u20105"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716948"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.07.009"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.09.014"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.5959"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2023.12.023"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.12.009"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20102027"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr\u201022\u201022"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001982\u20102"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2022.07.604"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01891"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113469"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70149"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.10613"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.350"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02747"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.117"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01476"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon\u20102023\u20100602"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201024\u201001544"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T11:26:34Z","timestamp":1766748394000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.71469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":33,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/cam4.71469"],"URL":"https:\/\/doi.org\/10.1002\/cam4.71469","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2024-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71469"}}