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 Journal Article

  

Authors:	Picozzi, V. J.; Ramanathan, R. K.; Lowery, M. A.; Ocean, A. J.; Mitchel, E. P.; O'Neil, B. H.; Guarino, M. J.; Conkling, P. R.; Cohen, S. J.; Bahary, N.; Frank, R. C.; Dragovich, T.; Bridges, B. B.; Braiteh, F. S.; Starodub, A. N.; Lee, F. C.; Gribbin, T. E.; Richards, D. A.; Lee, M.; Korn, R. L.; Pandit-Taskar, N.; Goldsmith, S. J.; Intenzo, C. M.; Sheikh, A.; Manzone, T. C.; Horne, H.; Sharkey, R. M.; Wegener, W. A.; O'Reilly, E. M.; Goldenberg, D. M.; Von Hoff, D. D.
Article Title:	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
Abstract:	Background 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 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. Methods Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N = 29, 90Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m2 doses × 3, plus gemcitabine, weekly 200 mg/m2 doses × 4 starting 1 week earlier) or Arm B (N = 29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m2 doses × 3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. Results 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; P = 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, P = 0.004), including three patients in Arm A surviving >1 year. Conclusions Clinical studies of 90Y-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. © 2015 The Authors.
Keywords:	adult; cancer survival; treatment response; major clinical study; overall survival; constipation; fatigue; neutropenia; ascites; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; gastrointestinal hemorrhage; hypertension; side effect; gemcitabine; anorexia; low drug dose; anemia; bleeding; leukopenia; nausea; thrombocytopenia; vomiting; dehydration; abdominal pain; asthenia; backache; chill; coughing; dyspnea; fever; alkaline phosphatase; aspartate aminotransferase; acute kidney failure; hyponatremia; immunogenicity; peripheral edema; pancreas adenocarcinoma; pleura effusion; alkaline phosphatase blood level; hyperbilirubinemia; bacteremia; headache; pancreatic cancer; phase 1 clinical trial; radioimmunotherapy; antibody; cerebrovascular accident; abdominal distension; disseminated intravascular clotting; yttrium-90; human; male; female; priority journal; article; patient history of chemotherapy; clivatuzumab tetraxetan; clivatuzumab tetraxetan y 90
Journal Title:	European Journal of Cancer
Volume:	51
Issue:	14
ISSN:	0959-8049
Publisher:	Elsevier Inc.
Date Published:	2015-09-01
Start Page:	1857
End Page:	1864
Language:	English
DOI:	10.1016/j.ejca.2015.06.119
PROVIDER:	scopus
PUBMED:	26187510
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84939550103&partnerID=40&md5=90bdeb40967069cec6e0705dcd0231c2
Notes:	Export Date: 2 September 2015 -- Source: Scopus

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