Presentation is loading. Please wait.

Presentation is loading. Please wait.

Phase III Trial of Sunitinib (Su) vs Sorafenib (So) in Advanced Hepatocellular Carcinoma (HCC) A Cheng, Y Kang, D Lin, J Park, M Kudo, S Qin, M Omata,

Similar presentations


Presentation on theme: "Phase III Trial of Sunitinib (Su) vs Sorafenib (So) in Advanced Hepatocellular Carcinoma (HCC) A Cheng, Y Kang, D Lin, J Park, M Kudo, S Qin, M Omata,"— Presentation transcript:

1 Phase III Trial of Sunitinib (Su) vs Sorafenib (So) in Advanced Hepatocellular Carcinoma (HCC) A Cheng, Y Kang, D Lin, J Park, M Kudo, S Qin, M Omata, SW Pitman Lowenthal, S Lanzalone, L Yang, M Lechuga, E Raymond

2 SUN1170 Hepatocellular Carcinoma (HCC) Study—Background and Rationale Liver cancer is the third leading cause of cancer-related death worldwide 1 Approximately 80% of HCC cases are attributable to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 2 Sunitinib is an oral inhibitor of VEGFRs and other receptor tyrosine kinases implicated in HCC angiogenesis, lymphangiogenesis, and disease pathogenesis 3-5 In 3 phase II studies, sunitinib had encouraging antitumor activity in patients with advanced HCC 6-8 Clinical benefit rate: 38%-53%, TTP: months, OS: months The open-label, Phase III SUN1170 trial compared the efficacy and safety of sunitinib with that of sorafenib The SUN1170 trial was designed based on data from the sorafenib SHARP trial (median OS 10.7 months) 9 Clinical benefit rate=complete/partial response + stable disease; OS=overall survival; SHARP=Study of Heart and Renal Protection; TTP=time to tumor progression; VEGFRs=vascular endothelial growth factor receptors. 1. Ferlay J et al. Int J Cancer. 2010;127:2093; 2. Perz JF et al. J Hepatol. 2006;45:529; 3. Yao DT et al. Hepatobiliary Pancreat Dis Int. 2005;4:220; 4. Zhang ZL et al. World J Gastroenterol. 2006;12:4241; 5. Makinen. EMBO J. 2001;20:4752; 6. Faivre S et al. Lancet Oncol. 2009;10:794; 7. Zhu AX et al. J Clin Oncol. 2009;27:3027; 8. Koeberle D et al. Oncologist. 2010;15:285; 9. Llovet JM et al. N Engl J Med. 2008;359:378. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

3 SUN1170 HCC—Study Design N=1200 Sunitinib 37.5 mg/day CDD (n=600) Enrollment Criteria Advanced histologically confirmed HCC No prior systemic chemotherapy ECOG PS 0-1 Child-Pugh group A Stratification Region (Asia vs Ex-Asia) Prior TACE (≤3 vs >3 courses) Tumor invasion (presence vs absence of vascular invasions and/or extrahepatic spread) Sorafenib 400 mg BID (n=600) R A N D O M I Z AT I O N Endpoints Primary: OS Secondary –PFS –TTP –Safety Statistics Superiority/noninferiority design Hypothesis: increase in median OS from 10.7 to 13.3 months Noninferiority boundary of median OS (9.5, 11.5 months) 1-sided log-rank test; α=0.025, 90% power CDD=continuous daily dosing; ECOG PS=Eastern Cooperative Oncology Group performance status; PFS=progression-free survival; TACE=transarterial chemoembolization. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

4 Study Outcome The study was stopped after a planned safety review by an independent data monitoring committee (events: 457 deaths) Higher incidence of serious adverse events (AEs) with sunitinib resulted in an unfavorable risk-benefit relationship vs sorafenib Enrollment was halted after 1074 patients had been randomized from July 2008 to May 2010 Sunitinib discontinuation recommended and treatment changed to standard of care If continued clinical benefit, further sunitinib treatment possible based on investigator’s judgment Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

5 Baseline Patient Characteristics (ITT Population) Characteristic Sunitinib (n=530) Sorafenib (n=544) Median age (range), y59 (18-85)59 (18-84) Male gender (%)8284 Geographical region of Asia* (%)7675 Vascular invasion and/or extrahepatic spread* (%) 7976 Prior TACE* (%) ≤3 courses8483 >3 courses1517 ECOG PS of 1 (%)47 † 47 HBV/HCV infection (%)55/2153/22 CLIP score (%) /25857 ≥32928 BCLC Stage B/C (%) ‡ 13/87 § 16/83 *Stratification factor; † Includes 1 patient with ECOG performance status of 2; ‡ Staging assigned retrospectively; § Percentage of 529 patients. BCLC=Barcelona Clinic Liver Cancer; CLIP=Cancer of the Liver Italian Program; ITT=intent-to-treat. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

6 Baseline Patient Characteristics (ITT Population) (cont’d) Characteristic Sunitinib (n=530) Sorafenib (n=544) Number of involved disease sites per participant ≥32521 Involved disease sites Liver8991 Lung3638 Lymph nodes2724 Other organs3527 Medical history relevant to primary diagnosis Underlying cirrhosis5045 Partial or complete portal vein thrombosis3431 Esophageal varices2829 History of alcohol abuse1715 Nonalcoholic steatohepatitis33 Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

7 Treatment Administration (As-Treated Population) Sunitinib (n=526) Sorafenib (n=542) Median relative dose intensity (%)6771 Median no. treatment cycles started44 (range)(1-27)(1-31) Median no. weeks on study15 (range)( )( ) Median no. weeks on treatment1114 (range)( )( ) No. of patients with ≥1 year of treatment2655 Dose interruption, any cause (% of patients)6956 Dose reduction, any cause (% of patients)4869 Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

8 OS—Primary Endpoint (ITT Population) Sunitinib Sorafenib Time (months) OS probability (%) Sunitinib Median 7.9 months (95% CI: ) Sorafenib Median 10.2 months (95% CI: ) HR 1.30 (95% CI: ) P=.0010 Patients at risk P-value based on stratified log-rank test. CI=confidence interval; HR=hazard ratio. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

9 Progression-Free Survival (ITT Population) Sunitinib Sorafenib Time (months) PFS probability (%) Sunitinib Median 3.6 months (95% CI: ) Sorafenib Median 3.0 months (95% CI: ) HR 1.13 (95% CI: ) P=.1215 Patients at risk P-value based on stratified log-rank test. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

10 Tumor Response (ITT Population: Investigator Assessment) Best Objective Response 1 n, (%) Sunitinib (n=530) Sorafenib (n=544) Complete response2 (<1)1 (<1) Partial response33 (6)32 (6) Stable disease (≥12 weeks)232 (44)247 (45) Clinical benefit rate*267 (51)280 (51) *Odds ratio for clinical benefit rate (95% CI): 1.03 ( ); P= Therasse P et al. J Natl Cancer Inst. 2000;92(3): Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

11 Subgroup Analysis of Efficacy Results (ITT Population—Asian vs Ex-Asian Region) Sunitinib (n=530) Sorafenib (n=544) Hazard ratio (95% CI)P-value* Median OS (months), ITT ( ).0010 Asian regions † ( ).0171 Ex-Asian regions ‡ ( ).0036 Median PFS (months), ITT ( ).1215 Asian regions ( ).3930 Ex-Asian regions ( ).0182 TTP (months), ITT ( ).1688 Asian regions ( ).3850 Ex-Asian regions ( ).0495 Ex-Asian regions=regions excluding Asia; ITT population (sunitinib=529; sorafenib=544). *P-value based on stratified log-rank test; † Asian population: sunitinib=402, sorafenib=410; ‡ Ex-Asian population: sunitinib=127, sorafenib=134. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

12 OS in Patients With HBV Infection (Exploratory Analysis) P-values based on stratified log-rank test. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL. OS probability (%) Time (months) Sunitinib ITT Sorafenib ITT Sunitinib Asia Sorafenib Asia Sunitinib Ex-Asia Sorafenib Ex-Asia Median OS, months HR (95% CI)1.10 ( )1.10 ( )1.08 ( ) P-value (1-sided) Sunitinib (n=290) Median 7.6 months (95% CI: ) Sorafenib (n=288) Median 8.0 months (95% CI: ) ITT Population HR 1.10 (95% CI: ) P=.1714

13 OS in Patients With HBV Infection (Exploratory Analysis) P-values based on stratified log-rank test. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL. Time (months) Sunitinib ITT Sorafenib ITT Sunitinib Asia Sorafenib Asia Sunitinib Ex-Asia Sorafenib Ex-Asia Median OS, months HR (95% CI)1.10 ( )1.10 ( )1.08 ( ) P-value (1-sided) Sunitinib (n=21) Median 7.9 months (95% CI: 5.5-not reached) Sorafenib (n=25) Median 15.3 months (95% CI: ) Ex-Asian regions HR 1.08 (95% CI: ) P=.3749 OS probability (%)

14 OS in Patients With HCV Infection (Exploratory Analysis) P-values based on stratified log-rank test. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL. OS probability (%) Time (months) Sunitinib ITT Sorafenib ITT Sunitinib Asia Sorafenib Asia Sunitinib Ex-Asia Sorafenib ex-Asia Median OS, months HR (95% CI)1.52 ( )1.40 ( )1.76 ( ) P-value (1-sided) Sunitinib (n=113) Median 9.2 months (95% CI: ) Sorafenib (n=119) Median 17.6 months (95% CI: 11.4-) ITT Population HR 1.52 (95% CI: ) P=.0165

15 Most Common Treatment-Emergent AEs (Grade* 3 or 4 in >5% of Patients; As-Treated Population) Sunitinib (%; n=526)Sorafenib (%; n=541) Hematologic AEsGrade 3Grade 4Grade 3Grade 4 Thrombocytopenia24641 Neutropenia2322<1 Leukopenia121<10 Anemia6331 Nonhematologic AEs Hand-foot syndrome13021<1 Increased AST8<19 Diarrhea7<190 Fatigue6<14 Asthenia6<140 Decreased appetite6040 *National Cancer Institute—Common Terminology Criteria for AEs (NCI-CTCAE) v3.0. AST=aspartate aminotransferase. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

16 Bleeding AEs (All Causes; As-Treated Population) Grade* (%) Sunitinib (n=526) Sorafenib (n=542) AllG3/4G5AllG3/4G5 Any bleeding Selected bleeding sites Gastrointestinal <1 Hepatic tumor1<1 0 *NCI-CTCAE v3.0. G=grade. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

17 Deaths on Study* (All Causes; As-Treated Population) Event Sunitinib (n=526) Sorafenib (n=542) Deaths (all causes; n, %)92 (17%)83 (15%) Cause (% of total deaths: SU n=92; SO n=83) † Disease progression76%86% Toxicity18%2% Dehydration ± organ failure3%0 CNS hemorrhage3%0 Esophageal varices/GI hemorrhage † 3%1% Other/unknown cause7%13% Pneumonia2%1% Septic shock/sepsis1%2% Unknown reason02% *Deaths during the study or within 28 days after the last dose of study medication. Participants may have more than one cause of death; † Includes deaths attributed to tumor hemorrhage. CNS=central nervous system; GI=gastrointestinal; SU=sunitinib; SO=sorafenib. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

18 Conclusions Sunitinib did not demonstrate superiority or noninferiority in OS, compared with sorafenib in patients with advanced HCC PFS, TTP, and ORR were comparable between treatment arms Frequency and severity of AEs were higher with sunitinib than sorafenib In patients with HBV infection, OS was similar between arms. In patients with HCV infection, OS was shorter with sunitinib ORR=overall response rate. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

19 Acknowledgements Thanks to all of the participating patients and their families, as well as the global network of investigators, research nurses, study coordinators, and operations staff This study was supported by funding from Pfizer Inc. Medical writing support was provided by Molly Heitz at ACUMED ® (Tytherington, UK) and was funded by Pfizer Inc. Adapted from Cheng A et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.


Download ppt "Phase III Trial of Sunitinib (Su) vs Sorafenib (So) in Advanced Hepatocellular Carcinoma (HCC) A Cheng, Y Kang, D Lin, J Park, M Kudo, S Qin, M Omata,"

Similar presentations


Ads by Google