Helping you access curative therapies for liver cancer patients

Transcription

1 Metastatic colorectal cancer (mcrc) Helping you access curative therapies for liver cancer patients Biocompatibles Excellence in Interventional Oncology Biocompatibles UK Ltd is a BTG International group company

2 DEBIRI withdc Bead is a liver-directed therapy which is well tolerated in colorectal patients with liver-dominant metastases 1,2 DEBIRI with DC Bead has been shown to offer the potential to downstage liver cancer patients to curative therapies by improving tumour response and delaying progression. 1,2 By protecting healthy liver, DEBIRI with DC Bead may help reduce hepatic insufficiency, specifically steatohepatitis, and reduce morbidity at resection. 2,3,4 DEBIRI with DC Bead : As a concomitant therapy with systemic chemotherapy in chemo-naïve patients As a neoadjuvant therapy in chemo-naïve patients prior to resection Giving mcrc patients more treatment options

3 Downstaging therapy DEBIRI withdc Bead concomitant with systemic therapy in chemo-naïve patients DEBIRI in Treatment of Chemo-Naïve Unresectable mcrc with Concomitant Systemic Fluorouracil and Oxaliplatin [FOLFOX]: Pharmacokinetics and Phase 1 Trial 1 PI: Robert Martin MD, University of Louisville School of Medicine, KY, USA Downstaging: 40% (4/10) downstaged to resection Pharmacokinetics: - Minimal detectable levels of CPT-11 and SN-38 at 24 hours after DEBIRI - No dose-limiting toxicity - No irinotecan-related systemic effects Median overall survival: 15.2 months Overall pathological response: >95% (resected specimens) Inclusion Criteria Chemo-naïve for metastatic disease One lesion >1cm (mrecist) Liver-dominant mcrc ( 80% tumour burden confined to liver) <60% liver replacement by tumour ECOG status 2 Life expectancy 3 months Adequate haematologic and liver function Response (mrecist) Liver-specific response 100% 100% 100% 100% 100% 90% 90% 80% 80% 70% 60% 60% 50% 50% 40% 30% 20% 10% 0% 3 Months 6 Months 9 Months 12 Months Martin RCG et al. J Gastrointest Surg 16 (2012): Overall response We demonstrated enhanced response rates, without added systemic effects and the ability to downstage patients to hepatic resection. Schema n=10 Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 FOLFOX DEBIRI FOLFOX DEBIRI FOLFOX FOLFOX +/ 100mg +/ 100mg +/ Break +/ Avastin Irinotecan Avastin Irinotecan Avastin Avastin

4 Neoadjuvant therapy DEBIRI withdc Bead a neoadjuvant therapy in chemo-naïve patients prior to resection Feasibility of Neoadjuvant DEBIRI with DC Bead for Resectable Liver Metastases 3 PI: Mr Graeme Poston, University Hospital Aintree, Liverpool, UK DEBIRI with DC Bead may offer: Improved response in target tissue 2,3,4 Protection of healthy liver due to targeted nature of drug delivery 2,3 Reduced risk of excessive bleeding due to sinusoidal congestion and thrombosis (systemic oxaliplatin) 3 Reduced risk of steatosis and steatohepatitis (systemic irinotecan), which can lead to post-operative liver failure and 90-day death 2,3 % Patients Pathological Response Rates after Treatment 4, % 22% 36% 59% FOLFOX/FOLFIRI DEBIRI Minor Major Complete > 50% residual cancer cells 1 to 49% residual cancer cells No residual cancer cells Pathological response 9% 17% The ability to administer effective high-dose cytotoxic irinotecan without inducing significant hepatic insufficiency, specifically steatohepatitis, is of utmost importance to hepatobiliary surgeons. Resection after neoadjuvant DEBIRI -TACE for CRLM [colorectal liver metastases] is feasible and well tolerated. Single treatment with DEBIRI -TACE resulted in tumour pathologic response similar to that seen after protracted systemic chemotherapy. Bower M et al. HPB (Oxford) 12 (2010): 31-6 Jones RP et al. J Clin Oncol 30 (2012): suppl; abstr 3613 Before DEBIRI 4 weeks after DEBIRI No DEBIRI : Viable liver tumour cells DEBIRI : Liver tumour cell death

5 Downstaging therapy DEBIRI withdc Bead a downstaging and neoadjuvant therapy in unresectable patients Surgical Downstaging and Neoadjuvant Therapy in Metastatic Colorectal Carcinoma with Irinotecan- Eluting Beads: A Multi-Institutional Study 2 PI: Matthew Bower MD, University of Louisville School of Medicine, KY, USA Downstaging: 20% (11/55) patients downstaged to resection or ablation Patient characteristics: - 30% patients were undergoing simultaneous systemic chemotherapy - Median number of lesions was 4 (range 1-20) - Median total size of target lesions was 9cm (range cm) - 50% of patients had bilobar tumour distribution Tumour Response (RECIST) 3 Months 6 Months 12 Months 18 Months Complete Response 6% 7% 6% 8% Partial Response 33% 35% 50% 83% Stable Disease 52% 54% 32% 0% Progressive Disease 9% 4% 12% 8% Inclusion Criteria Liver-dominant mcrc (>50% overall total disease burden) ECOG status <2 Life expectancy >3 months % Patients Extent of Liver Involvement % % 10% <25% 26-50% >50% Liver involvement The utilisation of precision hepatic arterial irinotecan infusion as a monotherapy or in conjunction with current systemic chemotherapy opens up multiple opportunities in optimising patients with high-risk colorectal cancer. Bower M et al. HPB (Oxford) 12 (2010): 31-6 Giving mcrc patients more treatment options

6 Surgical Oncology References: 1 Martin RCG, Scoggins CR, Tomalty D et al. J Gastrointest Surg 16 (2012): Bower M, Metzger T, Robbins K et al. HPB (Oxford) 12 (2010): Poston G, Presentation (Satellite Symposium), IHPBA Paris, France, 3 July Jones RP, Malik HZ, Fenwick SW et al. J Clin Oncol 30, 2012 (suppl; abstr 3613) 5 Blazer DG, Kishi Y, Maru DM et al. J Clin Oncol 26 (2008): Important Safety Information DC Bead Indications: DC Bead is CE marked and is indicated for the treatment of malignant hypervascular tumours and loading with doxorubicin drug DC Bead is also indicated for loading with irinotecan for the treatment of metastatic colorectal cancer (mcrc) For full instructions for use, please refer to: DC Bead M1 Indications: DC Bead M1 is primarily intended as an embolic agent for the treatment of malignant hypervascularised tumour(s) DC Bead M1 is compatible with irinotecan, which can be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and sustained dose to the mcrc after embolisation DC Bead M1 is compatible with doxorubicin, which can be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and sustained dose to the tumour after embolisation For full instructions for use, please refer to: Both products and/or all indications may not be available in your territory. DC Bead and DC Bead M1 are not cleared by the FDA for sale or distribution in the USA. DC Bead and DC Bead M1 are manufactured by Biocompatibles UK Ltd. Cautions: DC Bead and DC Bead M1 Embolisation with DC Bead/DC Bead M1 should only be performed by a physician with appropriate interventional occlusion training in the region intended to be embolised Do not use if the vial or packaging appear damaged Ensure that DC Bead/DC Bead M1 is an appropriate size for the intended vasculature Consider upsizing to a larger size of DC Bead in the presence of AV shunts or if angiographic evidence of embolisation does not appear quickly during delivery Consideration should be given to Tc99m-MAA scanning if there is suspicion of AV shunting Cautions: Irinotecan-loaded DC Bead and DC Bead M1 On addition of non-ionic contrast/water mixture to irinotecan-loaded beads, some irinotecan will be eluted over time. If the beads are not used immediately, up to 10mg irinotecan may be present in the contrast/water mixture. If this occurs, a small dose of irinotecan may be available systemically at time of delivery Do not use irinotecan-loaded beads with contrast agents containing salts (e.g. Calcium chloride) The maximum amount of irinotecan that can be loaded is 100mg irinotecan per vial of DC Bead/DC Bead M1. Exceeding this amount may lead to some irinotecan remaining free in solution. This free solution should be removed prior to use to prevent the patient receiving the excess dose as a bolus Cautions: Doxorubicin-loaded DC Bead and DC Bead M1 Exceeding a loading dose of 37.5mg doxorubicin per 1ml DC Bead/DC Bead M1 may lead to some systemic distribution of doxorubicin and related side effects Potential Complications: DC Bead and DC Bead M1 Undesirable reflux or passage of DC Bead/DC Bead M1 into normal arteries adjacent to the targeted lesion or through the lesion into other arteries or arterial beds Non-target embolisation Pulmonary embolisation Ischaemia at an undesirable location Capillary bed saturation and tissue damage Ischaemic stroke or ischaemic infarction Vessel or lesion rupture and haemorrhage Neurological deficits including cranial nerve palsies Vasospasm Death Recanalisation Foreign body reactions necessitating medical intervention Infection necessitating medical intervention Clot formation at the tip of the catheter and subsequent dislodgement causing arterial thromboembolic sequelae WARNING: Studies have shown that DC Bead and DC Bead M1 do not form aggregates and, as a result, penetrate deeper into the vasculature as compared to similarly sized PVA particles. Ordering Information: Product Name DC Bead M1 DC Bead Label Colour and Size µm µm µm µm Volume of Beads Product Code DC2V001 DC2V103 DC2V305 DC2V507 For more information, please contact: Biocompatibles UK Limited Chapman House, Farnham Business Park Weydon Lane, Farnham, Surrey, GU9 8QL, UK Tel: +44 (0) Fax: +44 (0) marketing@biocompatibles.com DC Bead, DC Bead M1 and DEBIRI are trademarks of Biocompatibles UK Ltd; DC Bead is a registered trademark in US, EU, China, Japan, South Korea; DEBIRI is a registered trademark in US and EU. Biocompatibles UK Ltd is a BTG International group company. BTG and the BTG roundel are registered trademarks of BTG International Ltd in US, EU and certain other territories and trademarks of BTG International Ltd elsewhere. DC Bead and DC Bead M1 are not currently cleared by the FDA for sale or distribution in the USA. Copyright 2013 Biocompatibles UK Ltd. GxUS-DCB Rev 1. Biocompatibles Excellence in Interventional Oncology Biocompatibles UK Ltd is a BTG International group company