{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:06:21Z","timestamp":1792872381941,"version":"4.5.0"},"reference-count":33,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,1,16]]},"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Response rates to single agent immune checkpoint blockade in unselected pretreated HER2\u2212negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200\u2009mg intravenously day 1 and capecitabine 1000\u2009mg\/m<jats:sup>2<\/jats:sup> by mouth twice daily on days 1\u201314 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0\u20136) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD&gt;6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial results\" xlink:href=\"NCT03044730\">NCT03044730<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2019-000173","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T04:35:13Z","timestamp":1581654913000},"page":"e000173","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2\u2212negative endocrine-refractory metastatic breast cancer"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct03044730","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"nct02752685","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03371017","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-3782","authenticated-orcid":false,"given":"Ami N","family":"Shah","sequence":"first","affiliation":[{"name":"Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Flaum","sequence":"additional","affiliation":[{"name":"Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Helenowski","sequence":"additional","affiliation":[{"name":"Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar A","family":"Santa-Maria","sequence":"additional","affiliation":[{"name":"Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarika","family":"Jain","sequence":"additional","affiliation":[{"name":"Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Rademaker","sequence":"additional","affiliation":[{"name":"Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Nelson","sequence":"additional","affiliation":[{"name":"Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, 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