1. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer Agnes Y. Y. Lee, MD, MSc; Pieter W. Kamphuisen, MD, PhD; Guy Meyer, MD; Rupert Bauersachs, MD; Mette S. Janas, MD, PhD; Mikala F. Jarner, MSc; Alok A. Khorana, MD; for the CATCH Investigators Amy Patel, PGY-3 March 17, 2016

2. Objective To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer.

3. Background Venous thromboembolism common cause of M&M in cancer patients. LMWH recommended over VKA based on a single, large RCT > 10 years ago

4. Study Population Age > 18 years old w/ cancer and acute DVT and/or PE Active cancer with histologic confirmation – Diagnosed within the last 6 months, recurrent, regionally advanced or mets – Treatment in previous 6 months – ECOG 0, 1, or 2

5. Study Population Exclusion criteria – CrCl 72 hours, or on AC at time of VTE, life expectancy < 6 months, “unlikely to comply,” or participating in another study, women of childbearing age or fertile men not using contraception

6. Randominazation Within 72 hours of VTE All had imaging for DVT and PE Stratified by tumor extent, geographic region, and history of VTE

7. Interventions Tinzaparin 175 IU/kg once daily SC x 6 months Warfarin 6 months with a 5-10 day bridge with tinzaparin until therapeutic INR for 2 days. Warfarin group had INR tested q2 weeks Temporary interruption for no more than 3 weeks for platelets < 50K, bleeding event, or procedures

8. Outcomes Primary outcomes – symptomatic DVT, nonfatal PE, fatal PE on autopsy, incidental proximal DVT or PE found on staging imaging. Safety outcomes – major bleeding, clinically relevant nonmajor bleeding, all-cause mortality.

9. Follow up Visits at 7, 14, 30, every 30 days. Weekly phone visits

10. Results 900 patients from 32 countries with a 91% completion of scheduled follow up Balanced groups Majority had solid tumors (90%) Time in therapeutic INR in warfarin group was 47%.

11. Baseline Characteristics

13. Results

15. Discussion Study states that LMWH did not significantly reduce composite recurrent VTE. Not associated with reductions in mortality or major bleeding Reduced risk of non major bleeding

16. Study Strengths/Weaknesses Strength – International study (as opposed to prior trial that was N. America and Europe) – Shares similar characteristics to the other trial Weakness – Tinzaparin not used in US – TTR on 47%? – No NOAC

17. Discussion Change in cancer treatments over 10 years may account for changes Not powered to analyze differences between cancer types Open-label design, no sham testing of INR in Tinzaparin group or sham injections in VKA group.

18. Study Conclusions Full dose Tinzaparin vs. VKA was not associated with reduced mortality, major bleeding or recurrent VTE, but was associated with a lower rate of nonmajor bleeding.

19. Questions?