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Abstract No. 140: Phase II trial of bevacizumab combined with transarterial chemoembolization (TACE) for hepatocellular carcinoma: Initial experience at two institutions
Purpose: Although loco-regional therapies continue to establish a role in the management of HCC, there remain important gaps in knowledge regarding imaging and survival outcomes. The purpose of this analysis was to present comprehensive imaging (time-to-progression: TTP) and long-term survival outcomes following chemoembolization for hepatocellular carcinoma (HCC). Materials and Methods: 172 HCC patients treated with chemoembolization were studied. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size, necrosis) and TTP. Overall survival from first chemoembolization was calculated. Sub-analyses were performed stratifying the population by Child-Pugh, UNOS and BCLC staging systems.
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Abstract No. 140
FEATURED ABSTRACT Phase II trial of bevacizumab combined with transarterial chemoembolization (TACE) for hepatocellular carcinoma: Initial experience at two institutions D. Reyes1, J.A. Vossen1, I. Kamel1, M.F. Mulcahy2, R. Salem3, W. Messersmith4, C. Weekes4, C. Georgiades1, K. Hong1, J.H. Geschwind1; 1Johns Hopkins University School of Medicine, Baltimore, MD; 2Hematology/Oncology, Northwestern University School of Medicine, Chicago, MD; 3Radiology, Northwestern University School of Medicine, Chicago, MD; 4University of Colorado Denver School of Medicine, Denver, CO. Purpose: This phase II study was performed to evaluate tumor response and safety of concurrent bevacizumab and transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Evidence of increased vascular endothelial growth factor activity in patients with HCC, and evidence that TACE stimulates angiogenic activity, led us to hypothesize that efficacy of TACE would be enhanced if given concurrently with an antiangiogenic agent. Materials and Methods: Patients seen with unresectable HCC were sequentially invited to participate. Those with ECOG 0-2, Childs-Pugh stage A-B, BCLC A-C were enrolled (to date, 26 patients including 21 males; mean age 64 yrs; ECOG 0-1 (n⫽25); Child’s A (n⫽20)). Therapeutic protocol was bevacizumab (Genentech, CA) 10 mg/kg every two weeks (half life 20 days), TACE week three, in a
Conclusion: Concurrent TACE and bevacizumab is reasonably well tolerated in unresectable HCC patients, with 100% disease control rate by imaging criteria and 13.5 months median overall survival. Small sample size is a limitation. The results support the concept of TACE with a concurrent anti-angiogenic agent. 11:15 AM
Abstract No. 141
Phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: Interim safety analysis D. Reyes1, N. Azad2, A. Koteish3, I. Kamel1, J. Hamilton3, C. Georgiades1, T. Pawlik4, M. Choti4, J.H. Geschwind1; 1 Radiology, Johns Hopkins University School of Medicine, Baltimore, MD; 2Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; 3Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD; 4Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. Purpose: Both sorafenib and transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE) have shown to have a survival advantage in patients with hepatocellular carcinoma (HCC). The purpose of this Phase II study was to evaluate the safety of combining sorafenib and DEB-TACE in 50 patients with unresectable HCC, with an interim safety analysis after the initial 8 patients. Materials and Methods: Patients with unresectable HCC and Child-Pugh A-B7, BCLC A-C, ECOG 0-1, and treatment naı¨ve were eligible for the study (8 patients completed safety analysis; mean age 68 yrs; ECOG 0 (n⫽6); Child’s A (n⫽8). Therapeutic protocol consisted of sorafenib (Bayer, NJ) 400mg twice daily 1 week prior to DEB-TACE (BioCompatibles, London); followed by DEB-TACE in 6-week cycles (sorafenib held 3 days pre- and post- DEB-TACE). Interim safety assessment (CTCAE, V 3.0) was performed to determine whether combination therapy exceeded expected toxicities from either therapy alone. Tumor response was assessed by RECIST and EASL criteria using MRI at baseline and 3 weeks post DEBTACE, every 1-2 cycles thereafter. Results: Grade 3-4 toxicities (any cause) were reported in 6/8 (63%) patients after 8th patient completed Cycle 1 (13 cycles combination therapy in total). Toxicities were not significantly greater (20%) than those seen in DEB-TACE alone (55%). Grade 3-4 toxicities were hematologic 4/8(50%), hand skin foot reaction 3/8(38%), fatigue 3/8(38%), pain 2/8(25%), diS55
TUESDAY
Conclusion: The determination of TTP and overall survival in HCC is confounded by tumor biology and background cirrhosis. Endpoint analyses using imaging are challenging given the rapidly evolving methodologies using tumor size and necrosis as well as the staged treatments administered at different time points. This cohort analysis presents an initial attempt at identifying TTP in HCC patients treated with chemoembolization; these data may provide guidance for future clinical trial design.
Results: Median follow-up was 6 months (range 1.4-34). Patients received ⬍1- 3 cycles of TACE with bevacizumab. On follow-up, evaluable index lesions (n⫽23) decreased from 5.9cm to 5.2cm (p⬍0.0005). By RECIST, 8/23 (35%) achieved partial response, 15/23 (65%) had stable disease. Targeted tumors decreased in contrast enhancement from 91% to 28% (p⬍0.0005). By EASL criteria, 14/23 (60%) had complete or partial response, and 9/23 (40%) had stable disease. Disease control rate was 100% by both criteria while undergoing treatment. Median overall survival was 13.5 months (n⫽10 censored 8/09). 15/26 (58%) patients experienced grade 3/4 toxicities possibly related to either therapy. Ten (38%) patient’s toxicities resolved. The thirty day mortality rate was 4%.
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Results: Cirrhosis was present in 93%, portal hypertension in 81%. Eleven (6%) patients had metastases at baseline. Portal vein thrombosis was present in eleven patients (6%). 55% of patients experienced any toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. 588 scans were reviewed to assess response and TTP. 31% and 64% of the patients responded according to size and necrosis criteria, respectively. Overall TTP was 7.9 mo (95% CI: 7.1-9.4) but varied by stage. Overall survivals of BCLC A, B and C patients were significantly different (A: 40.0 mo, B: 17.4 mo, C: 6.3 mo, P⬍0.0001).
6-week cycle. Primary endpoint was tumor response, assessed by MR imaging at baseline, and 3 weeks post TACE, using size (RECIST), and contrast-enhancement (EASL). Secondary endpoints included safety (CTCAE, V 3.0) and survival. P-values calculated with t-tests.
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Abstract No. 140
FEATURED ABSTRACT Phase II trial of bevacizumab combined with transarterial chemoembolization (TACE) for hepatocellular carcinoma: Initial experience at two institutions D. Reyes1, J.A. Vossen1, I. Kamel1, M.F. Mulcahy2, R. Salem3, W. Messersmith4, C. Weekes4, C. Georgiades1, K. Hong1, J.H. Geschwind1; 1Johns Hopkins University School of Medicine, Baltimore, MD; 2Hematology/Oncology, Northwestern University School of Medicine, Chicago, MD; 3Radiology, Northwestern University School of Medicine, Chicago, MD; 4University of Colorado Denver School of Medicine, Denver, CO. Purpose: This phase II study was performed to evaluate tumor response and safety of concurrent bevacizumab and transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Evidence of increased vascular endothelial growth factor activity in patients with HCC, and evidence that TACE stimulates angiogenic activity, led us to hypothesize that efficacy of TACE would be enhanced if given concurrently with an antiangiogenic agent. Materials and Methods: Patients seen with unresectable HCC were sequentially invited to participate. Those with ECOG 0-2, Childs-Pugh stage A-B, BCLC A-C were enrolled (to date, 26 patients including 21 males; mean age 64 yrs; ECOG 0-1 (n⫽25); Child’s A (n⫽20)). Therapeutic protocol was bevacizumab (Genentech, CA) 10 mg/kg every two weeks (half life 20 days), TACE week three, in a
Conclusion: Concurrent TACE and bevacizumab is reasonably well tolerated in unresectable HCC patients, with 100% disease control rate by imaging criteria and 13.5 months median overall survival. Small sample size is a limitation. The results support the concept of TACE with a concurrent anti-angiogenic agent. 11:15 AM
Abstract No. 141
Phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: Interim safety analysis D. Reyes1, N. Azad2, A. Koteish3, I. Kamel1, J. Hamilton3, C. Georgiades1, T. Pawlik4, M. Choti4, J.H. Geschwind1; 1 Radiology, Johns Hopkins University School of Medicine, Baltimore, MD; 2Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; 3Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD; 4Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. Purpose: Both sorafenib and transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE) have shown to have a survival advantage in patients with hepatocellular carcinoma (HCC). The purpose of this Phase II study was to evaluate the safety of combining sorafenib and DEB-TACE in 50 patients with unresectable HCC, with an interim safety analysis after the initial 8 patients. Materials and Methods: Patients with unresectable HCC and Child-Pugh A-B7, BCLC A-C, ECOG 0-1, and treatment naı¨ve were eligible for the study (8 patients completed safety analysis; mean age 68 yrs; ECOG 0 (n⫽6); Child’s A (n⫽8). Therapeutic protocol consisted of sorafenib (Bayer, NJ) 400mg twice daily 1 week prior to DEB-TACE (BioCompatibles, London); followed by DEB-TACE in 6-week cycles (sorafenib held 3 days pre- and post- DEB-TACE). Interim safety assessment (CTCAE, V 3.0) was performed to determine whether combination therapy exceeded expected toxicities from either therapy alone. Tumor response was assessed by RECIST and EASL criteria using MRI at baseline and 3 weeks post DEBTACE, every 1-2 cycles thereafter. Results: Grade 3-4 toxicities (any cause) were reported in 6/8 (63%) patients after 8th patient completed Cycle 1 (13 cycles combination therapy in total). Toxicities were not significantly greater (20%) than those seen in DEB-TACE alone (55%). Grade 3-4 toxicities were hematologic 4/8(50%), hand skin foot reaction 3/8(38%), fatigue 3/8(38%), pain 2/8(25%), diS55
TUESDAY
Conclusion: The determination of TTP and overall survival in HCC is confounded by tumor biology and background cirrhosis. Endpoint analyses using imaging are challenging given the rapidly evolving methodologies using tumor size and necrosis as well as the staged treatments administered at different time points. This cohort analysis presents an initial attempt at identifying TTP in HCC patients treated with chemoembolization; these data may provide guidance for future clinical trial design.
Results: Median follow-up was 6 months (range 1.4-34). Patients received ⬍1- 3 cycles of TACE with bevacizumab. On follow-up, evaluable index lesions (n⫽23) decreased from 5.9cm to 5.2cm (p⬍0.0005). By RECIST, 8/23 (35%) achieved partial response, 15/23 (65%) had stable disease. Targeted tumors decreased in contrast enhancement from 91% to 28% (p⬍0.0005). By EASL criteria, 14/23 (60%) had complete or partial response, and 9/23 (40%) had stable disease. Disease control rate was 100% by both criteria while undergoing treatment. Median overall survival was 13.5 months (n⫽10 censored 8/09). 15/26 (58%) patients experienced grade 3/4 toxicities possibly related to either therapy. Ten (38%) patient’s toxicities resolved. The thirty day mortality rate was 4%.
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Results: Cirrhosis was present in 93%, portal hypertension in 81%. Eleven (6%) patients had metastases at baseline. Portal vein thrombosis was present in eleven patients (6%). 55% of patients experienced any toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. 588 scans were reviewed to assess response and TTP. 31% and 64% of the patients responded according to size and necrosis criteria, respectively. Overall TTP was 7.9 mo (95% CI: 7.1-9.4) but varied by stage. Overall survivals of BCLC A, B and C patients were significantly different (A: 40.0 mo, B: 17.4 mo, C: 6.3 mo, P⬍0.0001).
6-week cycle. Primary endpoint was tumor response, assessed by MR imaging at baseline, and 3 weeks post TACE, using size (RECIST), and contrast-enhancement (EASL). Secondary endpoints included safety (CTCAE, V 3.0) and survival. P-values calculated with t-tests.