Abstract
Purpose
The phase II TACTIC trial prospectively selected patients with KRAS wild-type advanced biliary tract cancer for first-line treatment with panitumumab and combination chemotherapy.
Methods
Of 78 patients screened, 85 % had KRAS wild-type tumours and 48 were enrolled. Participants received cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8 of each 21-day cycle and panitumumab 9 mg/kg on day 1 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or request to discontinue. The primary endpoint was the clinical benefit rate (CBR) at 12 weeks (complete response, partial response, or stable disease). CBR of 70 % was considered to be of clinical interest. Secondary outcomes were progression-free survival, time to treatment failure, overall survival, CA19.9 response and safety.
Results
Thirty-four patients had a clinical benefit at 12 weeks, an actuarial rate of 80 % (95 % CI 65–89 %). 46 % had a complete or partial response. Median progression-free survival was 8.0 months (95 % CI 5.1–9.9) and median overall survival 11.9 months (95 % CI 7.4–15.8). Infection accounted for 27 % of the grade 3 or 4 toxicity, with rash (13 %), fatigue (13 %), and hypomagnesemia (10 %) among the more common grade 3 or 4 non-haematological toxicities.
Conclusion
A marker-driven approach to patient selection was feasible in advanced biliary tract cancer in an Australian population. The combination of panitumumab, gemcitabine, and cisplatin in KRAS wild-type cancers was generally well tolerated and showed promising clinical efficacy. Further exploration of anti-EGFR therapy in a more selected population is warranted.
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Acknowledgments
The authors thank John Simes for helpful comments and Rhana Pike for assistance with the manuscript.
Funding
This work was supported by an unrestricted educational grant provided by Amgen.
TACTIC
Trial Management Committee
J Shannon (Chair), D Goldstein, N Tebbutt, S Ng, M Cronk, C Karapetis, K Sjoquist, C Aiken
Independent Data Safety Monitoring Committee
VDo (Chair), I Marschner, M Friedlander, H Gurney
Clinical Trials Centre
J Simes, W Hague, R O’Connell, V Gebski, C Aiken, M Gorzeman, R Pike, K Miranda
Centre for Translational Pathology
P Waring, D Ferraro
Olivia Newton-John Cancer Research Institute
D Lau
Peter MacCallum Cancer Centre
S Fox
The following study sites participated in the [TACTIC] study and randomized at least one patient (principal investigator and site coordinator)
Austin Health, Victoria—N Tebbutt, Y Liu
Concord RG Hospital, New South Wales—P Beale, R Wykes
Icon Cancer Care, Queensland—P Vasey, T Wood
Nambour General Hospital, Queensland—M Cronk, C Cocks/K Simmons
Nepean Hospital, New South Wales—J Shannon, J McCourt
Peter MacCallum Cancer Centre, Victoria—M Jefford, A Hobinchet
Royal Prince Alfred Hospital, New South Wales—P Grimison, B Mirco/J Sagong
Sir Charles Gairdner Hospital, Western Australia—S Ng, S Dudukovic
Southern Medical Day Care Centre, New South Wales—M Aghmesheh, S Parker
St Vincent’s Hospital, New South Wales—E Segelov, L Ratnayake
St Vincent’s Hospital, Victoria—S McLachlan, N Ranieri
Townsville Hospital, Queensland—S Varma, J Page/E Heyer
Tweed Hospital, New South Wales—E Abdi, C Chorlton
Western Health, Victoria—L Lipton, L Wilkinson/I Marshall
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DG: research funding, Celgene Corporation, Amgen, Pfizer and Glaxo Smith Kline; JRZ: honoraria, financial support for attending symposia and research funding, Amgen, Merck Serono; CSK: advisory role with Amgen; NCT: research funding by Amgen. All remaining authors have declared no conflicts of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Ferraro, D., Goldstein, D., O’Connell, R.L. et al. TACTIC: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. Cancer Chemother Pharmacol 78, 361–367 (2016). https://doi.org/10.1007/s00280-016-3089-4
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DOI: https://doi.org/10.1007/s00280-016-3089-4