{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:38:31Z","timestamp":1790213911588,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Based on a high incidence of genomic alteration in the cell cycle and DNA damage and response (DDR)\u2010related pathways in small cell lung cancer (SCLC), the clinical efficacy of the DDR\u2010targeting agent olaparib (PARP inhibitor) as monotherapy and in combination with ceralasertib (ATR inhibitor) in relapsed or refractory SCLC was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>As part of a phase 2 biomarker driven umbrella study, patients with SCLC and predefined DDR gene alterations who failed to benefit from prior platinum\u2010based regimens were allocated to the olaparib monotherapy arm and nonbiomarker\u2010selected patients were allocated to the olaparib and ceralasertib combination arm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the olaparib monotherapy arm (<jats:italic>n<\/jats:italic>\u00a0=\u00a015), the objective response rate was 6.7% (one partial response), and the disease control rate was 33.3%, including three patients with stable disease. The median progression\u2010free survival was 1.3\u00a0months (95% CI, 1.2\u2013NA). In the combination arm (<jats:italic>n<\/jats:italic>\u00a0=\u00a026), the objective response rate and disease control rate were 3.8% and 42.3%, respectively, with one partial response and 10 patients with stable disease. The median progression\u2010free survival was 2.8\u00a0months (95% CI, 1.8\u20135.4). Treatment was generally well\u00a0tolerated except for one fatal case of neutropenic fever in the combination arm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Targeting DDR pathways with olaparib as a single agent or in combination with ceralasertib did not meet the predefined efficacy end point. However, disease stabilization was more evident in the combination arm. Further investigation of the combination of olaparib in SCLC should be performed with diverse combinations and patient selection strategies to maximize efficacy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35059","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T08:49:34Z","timestamp":1697446174000},"page":"541-552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biomarker\u2010driven phase 2 umbrella trial: Clinical efficacy of olaparib monotherapy and combination with ceralasertib (AZD6738) in small cell lung cancer"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-461X","authenticated-orcid":false,"given":"Sehhoon","family":"Park","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-0523","authenticated-orcid":false,"given":"Yu Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Department of Internal Medicine Seoul National University College of Medicine Seoul National University Bundang Hospital  Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Joo","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Ulsan University Hospital University of Ulsan College of Medicine  Ulsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G. 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