{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:59:02Z","timestamp":1789545542343,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Brain metastases are common in patients with lung and breast cancer and are associated with poor outcomes. While there is some intracranial activity with systemic therapies, most chemotherapies are minimally effective. Etirinotecan pegol (EP) is a PEGylated chemotherapy with favorable pharmacokinetics over irinotecan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a phase 2 trial of EP in patients with previously treated metastatic non\u2010small cell lung cancer (NSCLC, <jats:italic>n<\/jats:italic>\u2009=\u200912), small cell lung cancer (SCLC, <jats:italic>N<\/jats:italic>\u2009=\u20093) and breast cancer (MBC, <jats:italic>n<\/jats:italic>\u2009=\u200912), having progressive brain metastases after brain\u2010directed radiotherapy (or refusal). The primary endpoint was a 25% or greater disease control rate, defined as CR, PR+SD, in the central nervous system (CNS) at 12\u2009weeks; secondary endpoints included toxicity and systemic disease control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CNS control rate at 12\u2009weeks in NSCLC and MBC was 17% (two patients in each cohort) and 0% in SCLC. The median overall progression\u2010free survival for NSCLC was 2.7\u2009months (95% CI: 1.3, 6.7) and MBC was 1.4\u2009months (95% CI: 1.3, 6.9). The most common adverse events were diarrhea (48%), nausea (48%) and fatigue (26%). Six patient deaths occurred in this study. Dehydration\/diarrhea (1) and neutropenic sepsis (3) from study treatment were at least possibly related to these deaths.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that EP did not meet the threshold of clinical efficacy in patients with refractory CNS metastases from lung or breast cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.70330","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T02:38:46Z","timestamp":1756435126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Etirinotecan Pegol (<scp>NKTR<\/scp>\u2010102) in Patients With Active Brain Metastases From Lung or Breast Cancer"],"prefix":"10.1002","volume":"8","author":[{"given":"Seema","family":"Nagpal","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Neuro\u2010Oncology Stanford University  Stanford California 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