90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies. Issue 14 (September 2015)

• Record Type: Journal Article
• Authors: Picozzi, Vincent J.; Ramanathan, Ramesh K.; Lowery, Maeve A.; Ocean, Allyson J.; Mitchel, Edith P.; O'Neil, Bert H.; Guarino, Michael J.; Conkling, Paul R.; Cohen, Steven J.; Bahary, Nathan; Frank, Richard C.; Dragovich, Tomislav; Bridges, Benjamin B.; Braiteh, Fadi S.; Starodub, Alexander N.; Lee, Fa-Chyi; Gribbin, Thomas E.; Richards, Donald A.; Lee, Marie; Korn, Ronald L.; Pandit-Taskar, Neeta; Goldsmith, Stanley J.; Intenzo, Charles M.; Sheikh, Arif; Manzone, Timothy C.; Horne, Heather; Sharkey, Robert M.; Wegener, William A.; O'Reilly, Eileen M.; Goldenberg, David M.; Von Hoff, Daniel D.;
• Is Part Of: European journal of cancer. Volume 51:Issue 14(2015:Sep.)
• Page Start: 1857
• Page End: 1864
• Publication Date: 2015-09
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.06.119
• Languages: English
• ISSNs: 0959-8049

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st005">Abstract</title> <sec> <title id="st010">Background</title> <p id="sp0005">For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering <sup>90</sup>Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.</p> </sec> <sec> <title id="st015">Methods</title> <p id="sp0010">Fifty-eight patients with three (2–7) median prior treatments were treated on Arm A (<italic>N</italic> = 29, <sup>90</sup>Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m<sup>2</sup> doses × 3, plus gemcitabine, weekly 200 mg/m<sup>2</sup> doses × 4 starting 1 week earlier) or Arm B (<italic>N</italic> = 29, <sup>90</sup>Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m<sup>2</sup> doses × 3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.</p> </sec> <sec> <title id="st020">Results</title> <p id="sp0015">Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3–9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan–Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29–0.86; <italic>P </italic>= 0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, <italic>P </italic>= 0.004), including three patients in Arm A surviving >1 year.</p> </sec> <sec> <title id="st025">Conclusions</title> <p id="sp0020">Clinical studies of <sup>90</sup>Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.</p> </sec> </abstract>