LBA19 - A multi-institutional randomized phase 2 trial of the oncolytic virus reolysin in the first line treatment metastatic adenocarcinoma of the pancrea...

Date 28 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, non-colorectal
Topics Cancer Immunology and Immunotherapy
Pancreatic Cancer
Presenter Tanios Bekaii-Saab
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors T. Bekaii-Saab1, A.M. Noonan1, G. Lesinski1, S. Mikhail1, K. Ciombor1, S. Pant2, S. Aparo3, S. Tahiri1, A. Thompson1, J. Sexton1, J.L. Marshall4, T. Mace5, C. Wu1, B. El-Rayes6, C. Timmers5, S. Geyer5, J. Zwiebel7, M.A. Villalona-Calero8
  • 1Department Of Gastrointestinal Oncology, Ohio State University Medical Center, 43210 - Columbus/US
  • 2Medical Oncology, Oklahoma University, Stephenson Cancer Center, Oklahoma City/US
  • 3Medical Oncology, Albert Einstein College of Medicine, Montefiore Cancer Center, New York/US
  • 4Division Of Hematology/oncology, Georgetown University Medical Center, Washington/US
  • 5Osuccc, Ohio State University Medical Center, 43210 - Columbus/US
  • 6Medical Oncology, Emory University, Atlanta/US
  • 7Investigational Drug Branch, National Cancer Institute, Bethesda/US
  • 8Medical Oncology, Ohio State University Medical Center, 43210 - Columbus/US

Abstract

Aim

Reovirus is a naturally occurring virus that causes oncolysis in tumor cells with a Ras-activated pathway. It acts synergistically with taxanes. Since most pancreas cancer cells have downstream activated Ras we hypothesized that pts with MAP are susceptible to reovirus.

Methods

We conducted an NCI-sponsored phase II study with a goal of 70 evaluable MAP pts randomized in a 1:1 allocation to paclitaxel [P (175 mg/m2)], carboplatin [C (AUC 5)] on day 1 with reovirus [R (3 x 1010 TCID50) iv] on days 1-5 {Arm A} vs P/C alone {Arm B} on day 1 of a 21-day cycle. The primary endpoint is progression-free survival (PFS). Secondary endpoints include safety, objective response rate (ORR), and overall survival (OS). Pts progressing on B were allowed to crossover to A. Eligible pts had no prior chemotherapy. Pre-treatment tissue was required for KRAS mutation status from DNA analysis. Analyses of immunomodulatory effects of therapy were performed.

Results

Refer to Table 1 for key characteristics. Most common grade 3-4 toxicities include neutropenia (53%) and leucopenia (36%) with no overall difference between arms. In evaluable pts, ORR/SD was 22%/59% (A) and 21%/47% (B). To date, 81% have progressed, and median follow-up of 3.75 mo in event-free pts. PFS was similar in both arms (A: median 4.63 vs B: 5.1 mos; HR = 1.07, p = 0.81). The results held after sensitivity analyses and adjusting for factors such as KRAS. In 60 patients with KRAS analysis, a trend toward improved overall PFS in KRAS WT (6.0 mo) vs MT (4.3 mo); p = 0.20. In the KRAS MT group, an early limited differential in PFS between arm A (4.63 mo) vs B (4.34 mo); p = 0.73. 16 pts crossed over from B to A with 1 PR, 6 SD, 7 PD and 2 NA.

Characteristic Arm A Arm B p-value
Total N = 73 36 37
Age (Median, yrs) 61.5 66 0.055
ECOG PS (0/1), N 20/16 17/20 0.49
Baseline Ca 19-9 of > 59x ULN, % 53% 75% 0.14
KRAS Status ( MT), % 70% 77% 0.99
Pancreas Tumor Location, % Head Body Tail NS 22 36 22 22 27 38 19 14
Number of Metastatic Sites, % 1 2 >2 19 30 51 22 14 66 0.51

Conclusions

Reovirus can be administered safely in combination with P/C in pts with MAP. Both arms performed better than historical control, but R did not seem to improve outcome when added to P/C in MAP. This is the first report of P/C in MAP, which proved to have higher activity than anticipated, suggesting that similar to other disease settings, a relatively inexpensive taxane is an acceptable choice in MAP. A pharmaco-economic analysis is underway.

Disclosure

T. Bekaii-Saab: Research Funding: Oncolytics Biotech; M.A. Villalona-Calero: Research Grant : Oncolytics Biotech. All other authors have declared no conflicts of interest.