TY - JOUR
T1 - Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study)
AU - Le, Dung T.
AU - Picozzi, Vincent J.
AU - Ko, Andrew H.
AU - Wainberg, Zev A.
AU - Kindler, Hedy
AU - Wang-Gillam, Andrea
AU - Oberstein, Paul
AU - Morse, Michael A.
AU - Zeh, Herbert J.
AU - Weekes, Colin
AU - Reid, Tony
AU - Borazanci, Erkut
AU - Crocenzi, Todd
AU - LoConte, Noelle K.
AU - Musher, Benjamin
AU - Laheru, Dan
AU - Murphy, Aimee
AU - Whiting, Chan
AU - Nair, Nitya
AU - Enstrom, Amanda
AU - Ferber, Sandy
AU - Brockstedt, Dirk G.
AU - Jaffee, Elizabeth M.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/9/15
Y1 - 2019/9/15
N2 - Purpose: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX+CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed 2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. Results: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9- 5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95% CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred. Conclusions: The combination of Cy/GVAX+CRS-207 did not improve survival over chemotherapy.
AB - Purpose: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX+CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed 2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. Results: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9- 5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95% CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred. Conclusions: The combination of Cy/GVAX+CRS-207 did not improve survival over chemotherapy.
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U2 - 10.1158/1078-0432.CCR-18-2992
DO - 10.1158/1078-0432.CCR-18-2992
M3 - Article
C2 - 31126960
AN - SCOPUS:85072234431
SN - 1078-0432
VL - 25
SP - 5493
EP - 5502
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -