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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/m(2) and gemcitabine 1000 mg/m(2) 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. [ABSTRACT FROM AUTHOR]

Trifluridine/tipiracil is available on the Australian Pharmaceutical Benefits Scheme for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor agents and anti-epidermal growth factor receptor agents. This article reviews trifluridine/tipiracil clinical data and presents practical information on its use in the management of refractory mCRC in Australia. Whereas the primary mechanism of action of fluoropyrimidines such as fluorouracil (5-FU) and capecitabine is enzyme inhibition of nucleotide synthesis, trifluridine/tipiracil primarily acts by incorporation into DNA, resulting in DNA dysfunction. Trifluridine/tipiracil has activity in patients with 5-FU-resistant tumors and can be considered in patients with prior intolerance or toxicity to 5-FU. In the pivotal phase III RECOURSE trial evaluating trifluridine/tipiracil in chemotherapy-refractory mCRC, efficacy benefits were observed across all a priori prognostic subgroups including those defined by age (≥65 and ≥75 years), geographical origin, primary tumor site or KRAS status. Trifluridine/tipiracil therapy benefits appropriately selected patients who have an ECOG performance status of 0 or 1, with no more than mild hepatic impairment or mild-to-moderate renal impairment, and who are capable of adhering to oral therapy safely. Appropriate dosing, monitoring for adverse events and effective management of side effects are essential., (© 2020 John Wiley & Sons Australia, Ltd.)

Objectives: Given a lack of universally-accepted standard-of-care treatment for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), study objectives were to assess treatment utilization and survival outcomes for R/M HNSCC in the real-world setting., Materials and Methods: A multi-site retrospective chart review was conducted in Europe (Germany, United Kingdom, Italy, Spain), Asia Pacific (Australia, South Korea, Taiwan), and Latin/North America (Brazil and Canada) to identify patients who initiated first-line systemic therapy for R/M HNSCC between January 2011 and December 2013. Patients were followed through December 2015 to collect clinical characteristics, treatment and survival data., Results: Among 733 R/M HNSCC patients across 71 sites, median age was 60 years (inter-quartile range 54-67), 84% male, and 70% Eastern Cooperative Oncology Group performance status 0-1; 32% had oral cavity and 30% oropharyngeal cancers. The most common first-line regimen across all countries consisted of platinum-based combinations (73%), including platinum + 5-fluorouracil (5-FU) (26%), cetuximab + platinum ± 5-FU (22%), or taxane + platinum ± 5-FU (16%). However, use of different platinum-based combinations varied substantially; administration of cetuximab + platinum ± 5-FU was frequent in Italy (81%), Germany (46%) and Spain (38%), whereas use in other countries was limited. Median follow-up was 22.6 months (95% confidence interval [CI]: 21.5-24.6 months). Median real-world overall survival was only 8.0 months (95% CI: 7.0-8.0), with one-year survival reaching only 30.9% (95% CI: 27.5-34.3)., Conclusion: Systemic therapies used in clinical practice for patients with R/M HNSCC vary substantially across countries. Prognosis remains poor in this patient population, highlighting the need for newer, more efficacious treatments., Competing Interests: Declaration of Competing Interest Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Diana Chirovsky, Seongjung Joo and Roshani Shah are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Diana Chirovsky and Seongjung Joo additionally own stock options from Merck & Co., Inc., Kenilworth, NJ, USA. Hélène Kuyas, Valérie Auclair and Xavier Guillaume are employees of Kantar Health Division, which received funding to conduct and oversee the study. Viktor Grünwald reports honoraria from AstraZeneca, Bristol-Myers Squibb, Eisai, Ipsen, MSD, Merck Serono, Novartis, Pfizer and Roche, fees for advisory roles from AstraZeneca, Bristol-Myers Squibb, Ipsen, MSD, Merck Serono, Novartis, Pfizer and Roche, and research funding from AstraZeneca, Bristol-Myers Squibb, MSD, Novartis and Pfizer. Myung-Ju Ahn reports honoraria from Astra-Zeneca, MSD, Roche, BMS, Merck and Alphas Pharmaceutical. Gilberto Castro reports honoraria from MSD. Alfonso Berrocal reports honoraria from BMS, MSD, Roche, Novartis, Pierre Fabre, Merck-Pfizer, Sanofi and Incyte, fees for consultant or advisory roles from BMS, MSD, Roche, Novartis, Pierre Fabre, Merck-Pfizer, Sanofi and Incyte, and travel funding from BMS, MSD, Roche, Novartis, Pierre Fabre, Merck-Pfizer and Sanofi. Katrin Sjoquist reports honoraria from Pfizer, Merck and Amgen, and travel funding from Amgen and Ipsen. Kevin Harrington reports honoraria from AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck- Serono, and Merck Sharp Dohme, fees for advisory roles from AstraZeneca/MedImmune, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck- Serono, Merck Sharp Dohme and Pfizer, and research funding from AstraZeneca/MedImmune and Merck Sharp Dohme. The other authors declare no conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)