{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:08:47Z","timestamp":1790179727327,"version":"4.1.0"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Treatment options for patients with advanced penile squamous cell carcinoma who have disease progression on systemic chemotherapy are scarce. Antiangiogenic drugs have shown antitumor effects in case series. This phase 2 trial evaluated the activity and safety of apatinib (a Vascular Endothelial Growth Factor (VEGF) receptor inhibitor) in such patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This investigator-initiated, single-arm, phase 2 trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000021849) and performed at a tertiary cancer center in Shanghai, China. Eligible patients had histologically confirmed penile squamous cell carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, pretreated with one or more kinds of systemic treatment. Patients were prescribed oral apatinib 500\u2009mg daily with the option of dose reduction to manage adverse events. The primary endpoint was the investigator-assessed overall response rate (ORR) assessed in all patients who received at least one dose of study drug.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 2016 and 2023, we enrolled 23 patients, all of whom received at least one dose of study treatment. Of the 23 patients, 16 had an ECOG performance status of 2. Only 6 patients had human papillomavirus-positive tumors. Five patients had a partial response (ORR = 22% [95% CI, 10%-42%]). The median progression-free survival was 3.8\u2009months, and median overall survival was 7.2\u2009months. Treatment-related adverse events of grade 3 or worse occurred in 7 (30%) of 23 patients. The most common grade 3 or 4 treatment-related adverse events were hand\u2013foot syndrome (13%), hypertension (9%), and increase in serum alanine aminotransferase (9%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Apatinib in pretreated advanced penile cancer showed limited efficacy with a manageable safety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                    <jats:p>UMIN000021849.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag349","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:52:53Z","timestamp":1788616373000},"source":"Crossref","is-referenced-by-count":0,"title":["Apatinib monotherapy for pretreated advanced squamous cell carcinoma of the penis: a phase 2 trial"],"prefix":"10.1093","volume":"31","author":[{"given":"Juan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University , Shanghai 200032,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Affiliated Hospital of Qingdao University , Qingdao 266003,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University , Shanghai 200433,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0109-6951","authenticated-orcid":false,"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University , Shanghai 200032,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026092311562384200_oyag349-B1","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1200\/JCO.2015.63.5995","article-title":"Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction","volume":"34","author":"Li","year":"2016","journal-title":"J Clin Oncol"},{"key":"2026092311562384200_oyag349-B2","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1200\/JCO.23.02233","article-title":"Final results from a phase I trial and expansion cohorts of cabozantinib and nivolumab alone or with ipilimumab for advanced\/metastatic genitourinary tumors","volume":"42","author":"Apolo","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026092311562384200_oyag349-B3","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1200\/JCO.20.01652","article-title":"Phase I study of cabozantinib and nivolumab alone or with ipilimumab for advanced or metastatic urothelial carcinoma and other genitourinary tumors","volume":"38","author":"Apolo","year":"2020","journal-title":"J Clin Oncol"},{"key":"2026092311562384200_oyag349-B4","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1200\/JCO.22.02894","article-title":"Atezolizumab with or without radiotherapy for advanced squamous cell carcinoma of the penis (the PERICLES study): a phase II trial","volume":"41","author":"de Vries","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026092311562384200_oyag349-B5","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.euo.2020.10.011","article-title":"Association between human papillomavirus infection and outcome of perioperative nodal radiotherapy for penile carcinoma","volume":"4","author":"Bandini","year":"2021","journal-title":"Eur Urol Oncol"},{"key":"2026092311562384200_oyag349-B6","doi-asserted-by":"crossref","first-page":"e0300729","DOI":"10.1371\/journal.pone.0300729","article-title":"The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma","volume":"19","author":"Mumba","year":"2024","journal-title":"PLoS One"},{"key":"2026092311562384200_oyag349-B7","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.eururo.2024.03.038","article-title":"Single-cell atlas of penile cancer reveals TP53 mutations as a driver of an aggressive phenotype, irrespective of human papillomavirus status, and provides clues for treatment personalization","volume":"86","author":"Elst","year":"2024","journal-title":"Eur Urol"},{"key":"2026092311562384200_oyag349-B8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.eururo.2024.04.032","article-title":"TP53 mutations emerge as a critical biomarker in penile cancer, superseding human papillomavirus status","volume":"86","author":"Chahoud","year":"2024","journal-title":"Eur Urol"},{"key":"2026092311562384200_oyag349-B9","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/j.juro.2008.07.040","article-title":"The value of squamous cell carcinoma antigen in the prognostic evaluation, treatment monitoring and follow-up of patients with penile cancer","volume":"180","author":"Zhu","year":"2008","journal-title":"J Urol"},{"key":"2026092311562384200_oyag349-B10","doi-asserted-by":"crossref","first-page":"e7353","DOI":"10.1002\/cam4.7353","article-title":"Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen","volume":"13","author":"Ma","year":"2024","journal-title":"Cancer Med"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag349\/70984368\/oyag349.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/10\/oyag349\/70984368\/oyag349.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/10\/oyag349\/70984368\/oyag349.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:56:29Z","timestamp":1790178989000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyag349\/8787392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":10,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,9,9]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyag349","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,9,7]]},"article-number":"oyag349"}}