31P Efficacy and safety of utidelone in treatment-refractory advanced non-small cell lung cancer

Abstract

Chemotherapy remains the standard-of-care for most patients with advanced NSCLC. Utidelone, a genetically engineered epothilone analogue, demonstrated marked and durable antitumor activity in patients with metastatic breast cancer. Here, we reported the efficacy and safety of utidelone for advanced NSCLC refractory to second-line treatment. This was an open label, multicenter, phase II study (NCT03693547). Eligible criteria included age 18-70, ECOG performance status of 0-1, failure of previous standard second-line treatment (including platinum-containing chemotherapy with or without targeted therapy). All patients received the recommended dose of utidelone (40mg/m2/d intravenously on d1-d5, 21d per cycle). The primary endpoint was objective response rate (ORR). Safety was analyzed in all patients who received at least one dose of study treatment. From April 22, 2019 to January 22, 2021, 26 patients were enrolled, with a median age of 55.3 (range 39-68) years. 61.5% of patients had an ECOG PS of 1, 80.8% had adenocarcinoma, and 65% were pre-treated with taxol. At baseline, pre-treatment in the second-line, third-line, and fourth-line or over were present in 34.6%, 38.5%, and 26.9%, respectively. Efficacy was evaluated in full analysis set (FAS) (n=26) and per protocol set (PPS) (n=21) with an ORR of 15.4% (95% CI 4.4, 34.9) and 19.0% (95% CI 5.4, 41.9), respectively. DCR were 69.2% (95% CI 48.2, 85.7) and 81.0% (95% CI 58.1, 94.6) in FAS and PPS, respectively. The median PFS was 4.37 (95% CI 2.50 5.29) months in FAS and 4.37 (95% CI 2.50, 9.76) months in PPS. OS was not reached but 12 month-OS rate was 69.0% (95% CI 45.1%, 84.1%) in FAS and 71.0% (95% CI 42.7%, 87.1%) in PPS. 26 (100%) patients had at least one adverse event (AE), 2 (7.7%) experienced discontinuation of utidelone and 8 (30.8%) had a dose reduction. Common grade 3-4 AEs were peripheral neuropathy (19.2%, all were grade 3), lymphopenia (7.7%), elevated glutamyltransferase (7.7%), and hyponatremia (7.7%). Notably, low incidences of liver and renal toxicities, and very limited gastrointestinal toxic effect were observed. These findings demonstrate that utidelone may be an effective treatment option for advanced NSCLC refractory to second-line treatment.