Initial lenvatinib therapy with no prior TACE in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 522-522
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephen Lam Chan ◽  
Tomoko Aoki ◽  
Satoru Hagiwara ◽  
...  
Keyword(s):  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Progression Free Survival ◽  
Intermediate Stage ◽  
Hepatic Function ◽  
Phase Iii ◽  
Eligibility Criteria

522 Background: Intermediate-stage HCC is a heterogenous population with subgroups of patients that do not benefit from TACE. Hence, we conducted a matched cohort study to compare the efficacy of lenvatinib to TACE in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-7 criteria. Methods: This study first identified 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-7 criteria, without prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected. Propensity score matching was used to adjust for patients’ demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials [1 Phase II and 13 Phase III REFLECT trial], 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The lenvatinib group showed a higher objective response rate (73.3% vs. 33.3%; p < 0.001) and longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Median overall survival was also significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p < 0.01), respectively. Conclusions: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-7 criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib is associated with better outcome than TACE. In particular, leventinib is associated with preservation of hepatic function during treatment while TACE is associated with deterioration of hepatic function.

scholarly journals Lenvatinib as an Initial Treatment in Patients with Intermediate-stage Hepatocellular Carcinoma Beyond up-to-seven Criteria and Child-Pugh A Liver Function: A Proof-of-Concept Study

2019 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephan Chan ◽  
Tomohiro Minami ◽  
Hirokazu Chishina ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Unmet Need ◽  
Intermediate Stage ◽  
Proof Of Concept ◽  
Concept Study

Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p &lt; 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p &lt; 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p &lt; 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p &lt; 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.

scholarly journals Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1084 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephan Chan ◽  
Tomohiro Minami ◽  
Hirokazu Chishina ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Unmet Need ◽  
Intermediate Stage ◽  
Proof Of Concept ◽  
Concept Study

Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child–Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were −2.61 to −2.61 for 30 patients in the lenvatinib group (p = 0.254) and −2.66 to −2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child–Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 193-193 ◽  
Author(s):  
Eric Van Cutsem ◽  
Heinz-Josef Lenz ◽  
Junji Furuse ◽  
Josep Tabernero ◽  
Volker Heinemann ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Significant Prognostic Factor ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

193 Background: Pancreatic ductal adenocarcinoma (PDAC) is invariably diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant prognostic factor in PDAC progression and is associated with poor prognosis. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard (Br-IPM) that is preferentially activated under hypoxic conditions. The addition of Evo to gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m2 and 1,000 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), employing a hierarchical testing procedure with a 2-sided α=0.05 at each level. Results: A total of 693 pts were randomized to treatment with Evo/Gem (n=xxx) or Placebo/Gem (n=yyy). Baseline pt characteristics were similar between treatment arms. The OS HR was X.XX (95% CI: Y.YY, Z.ZZ; p=A.AAA). Median OS was AA.A months (m) for Evo/Gem vs BB.B m for Placebo/Gem. Median PFS was C.C m and D.D m, respectively (HR E.EE [95% CI: F.FF, G.GG; p = H.HHH). ORR was JJ.J% with Evo/Gem vs KK.K% with Placebo/Gem (p = L.LLL). Grade ≥3 adverse events (AEs) occurring in >5% of pts in treated with Evo/Gem were: TBC. Conclusions: The data from the MAESTRO trial will make an important contribution to our understanding of PDAC treatment. Clinical trial information: NCT01746979.

Phase II trial of chemoradiotherapy concurrent with S-1 plus cisplatin in patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN): Results of the Japan Clinical Oncology Group study, JCOG 0706.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5542-5542 ◽  
Author(s):  
Makoto Tahara ◽  
Naomi Kiyota ◽  
Junki Mizusawa ◽  
Kenichi Nakamura ◽  
Ryuichi Hayashi ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Complete Response ◽  
Phase Iii ◽  
Radiation Dermatitis ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Local Progression

5542 Background: To evaluate the efficacy and safety of chemoradiotherapy (CRT) concurrent with S-1 plus cisplatin in patients with unresectable locally advanced SCCHN. Methods: Eligibility criteria included histologically proven SCCHN with unresectable locally advanced lesions, PS 0-1, aged 20 to 75 years old, adequate organ function, and no prior treatment. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at 60 mg/m2/day, and cisplatin at 20 mg/m2/day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently startingon day 1. For patients achieving an objective response after CRT, two additional cycles of chemotherapy wereadministered. The primary endpoint was clinical complete response rate (%CR), which was the proportion of complete response (CR) and good partial response (good PR). Good PR was defined as remaining tissue with tumor shrinkage, which was not regarded as residual tumor but rather as scar material.The planned sample size was 45 patients, which was calculated by SWOG's two-stage attained design based on an expected %CR of 60% and a threshold of 45%, with a one-sided alpha of 0.1 and a power of 0.9. Results: From July 2008 to July 2010, 45 eligible subjects were accrued, including 43 males, with median age 63 years, ECOG PS 0/1 (36/9), oropharynx/ hypopharynx/larynx (26/15/4), T1/T2/T3/T4a/T4b (1/11/7/17/9) and N0/N2a/N2b/N2c/N3 (2/3/10/24/6). %CR was 64.4% (8 CR, 21 good PR) on central review. After a median follow-up of 1.56 years, 1-year local progression-free survival was 77.8%, with 1-year progression-free survival of 70.9%, 1-year overall survival of 93.3% and 1-year time to treatment failure of 57.6%. Grade 3 or 4 toxicity included mucositis (46.7%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%) and febrile neutropenia (4.4%). No treatment-related deaths were observed. Conclusions: This combination showed promising efficacy with acceptable toxicities. Further investigation in a phase III trial is planned.

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3616-3616 ◽  
Author(s):  
Allen Lee Cohn ◽  
J. Randolph Hecht ◽  
Shaker Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

3616 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (Table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III trial (ZODIAC)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA8003-CRA8003 ◽  
Author(s):  
R. S. Herbst ◽  
Y. Sun ◽  
S. Korfee ◽  
P. Germonpré ◽  
N. Saijo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Positive Trend ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

CRA8003 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Addition of vandetanib to docetaxel (doc) prolonged progression-free survival (PFS) in a randomized phase II study in patients (pts) with previously treated NSCLC (Heymach et al, JCO, 2007). Methods: The primary objective was to determine whether vandetanib 100 mg/day + doc 75 mg/m2 every 21 days (max 6 cycles) prolonged PFS vs placebo + doc. Secondary endpoints included overall survival, objective response rate (ORR), time to deterioration of symptoms (TDS) and safety. Efficacy and safety in females were assessed as a co-primary analysis population. Eligibility criteria included stage IIIB/IV NSCLC, PS 0–1, and previous first-line chemotherapy. Results: Between May 2006 and April 2008, 1,391 pts (mean age, 58 years; 30% female; 25% squamous; 10% brain mets) were randomized to vandetanib + doc (n=694) or placebo + doc (n=697). Baseline characteristics were similar in both arms. Median duration of follow-up was 12.8 months, with 87% patients progressed and 59% dead. Addition of vandetanib to doc showed a statistically significant improvement in PFS vs doc (hazard ratio [HR] 0.79, 97.58% CI 0.70–0.90; P<0.001), and a similar advantage in females (HR 0.79; P=0.024). Significant advantages for vandetanib + doc were also seen for ORR (17% vs 10%, P<0.001) and TDS (HR 0.78, P=0.002; FACT-L Lung Cancer Subscale). Overall survival showed a positive trend for vandetanib + doc that was not statistically significant (HR 0.91, 97.52% CI 0.78–1.07; P=0.196). The adverse event (AE) profile was consistent with that previously observed for vandetanib in NSCLC. Common AEs occurring more frequently in the vandetanib arm included diarrhea (42% vs 33%), rash (42% vs 24%) and neutropenia (32% vs 27%). Nausea (23% vs 32%), vomiting (16% vs 21%) and anemia (10% vs 15%) were less frequent in the vandetanib arm. The incidence of protocol-defined QTc prolongation was <2% in pts receiving vandetanib. Conclusions: The study met its primary objective of PFS prolongation with vandetanib + doc vs doc. Vandetanib is the first oral targeted therapy in phase III trials to show significant evidence of clinical benefit when added to standard chemotherapy in NSCLC. [Table: see text]

PEAK (study 20070509): A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild‑type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Randomized Phase Ii

446 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 1st-line tx in a phase III trial comparing pmab + FOLFOX4 vs FOLFOX4 alone. Here, we describe the results of PEAK, a multicenter, randomized phase II study evaluating pmab + mFOLFOX6 and bev + mFOLFOX6 in pts with previously untreated WT KRASmCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + mFOLFOX6 Q2W or bev 5.0 mg/kg + mFOLFOX6 Q2W. Pt eligibility criteria included: WT KRASmCRC, ECOG performance status ≤ 1, and no prior chemotherapy, anti-VEGF tx, or anti-EGFR tx for mCRC. The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 285 pts with WT KRASmCRC were randomized and 278 pts received tx. Demographics were balanced between arms. Intent-to-treat efficacy results are shown (Table). Worst grade 3/4 adverse events (AE) occurred in 86% of pts in the pmab + mFOLFOX6 arm vs 76% of pts in the bev + mFOLFOX6 arm. Grade 5 AEs occurred in 5% of pts in the pmab + mFOLFOX6 arm and 6% of pts in the bev + mFOLFOX6 arm. Tx discontinuation due to any AE was 24% in the pmab + mFOLFOX6 arm and 27% in the bev + mFOLFOX6 arm. Conclusions: In this estimation study of pts with WT KRASmCRC without any prior therapy for mCRC, PFS and ORR were similar between arms. The median OS was not reached in the pmab + mFOLFOX6 arm. The safety profile for both arms was consistent with previously reported studies of either combination. Tx discontinuation rates due to AEs were similar between arms. Clinical trial information: NCT00819780. [Table: see text]

Ramucirumab for patients with intermediate-stage hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): Pooled results from two phase III studies (REACH and REACH-2).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 549-549
Author(s):  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Manabu Morimoto ◽  
Kun-Ming Rau ◽  
Masafumi Ikeda ◽  
...  
Keyword(s):  
Liver Function ◽  
Meta Analysis ◽  
Objective Response ◽  
Intermediate Stage ◽  
Phase Iii ◽  
Locoregional Therapy ◽  
Two Phase ◽  
Linear Predictor ◽  
Bclc Staging ◽  
Grade 3

549 Background: Intermediate-stage HCC, as defined as Barcelona Clinic Liver Cancer (BCLC) Stage B, is a heterogeneous disease in terms of liver function and tumor load. REACH (NCT01140347) and REACH-2 (NCT02435433) investigated ramucirumab (RAM) in patients (pts) with HCC after prior sorafenib (SOR), with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: All pts had HCC (BCLC stage C or B disease refractory/not amenable to locoregional therapy), Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or Placebo (P) Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was performed. Prognosis of BCLC staging in overall survival (OS) was evaluated by multivariate Cox PH model (adjusted for baseline AFP and treatment (trt) arm); Trt effects in BCLC stage B and C by Cox PH model; median OS/PFS were estimated by Kaplan-Meier method. Objective response rate (ORR) per RECIST v1.1, disease control rate (DCR), and adverse events (AEs) were also reported by BCLC. Liver function was assessed at baseline and prior to each trt with the Albumin-Bilirubin (ALBI) linear predictor. Results: Baseline characteristics were generally balanced between trt arms in each BCLC stage. BCLC staging trended as an independent prognosis factor for OS [B v C; HR = 0.756 (0.546, 1.046)]. A consistent trt benefit for RAM v P was observed across staging (Table). Grade ≥3 AEs were consistent with observations from both individual studies; hypertension was the most frequent grade ≥3 AE. No difference in liver function, as measured by ALBI, was observed between trt arms in either BCLC stage. Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit irrespective of BCLC stage. RAM was well tolerated and did not alter liver function compared to P. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]

Baseline liver function and outcomes in the phase III REFLECT study in patients with unresectable hepatocellular carcinoma (uHCC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 524-524 ◽  
Author(s):  
Arndt Vogel ◽  
Catherine Frenette ◽  
Max W. Sung ◽  
Bruno Daniele ◽  
Ari David Baron ◽  
...  
Keyword(s):  
Liver Function ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Post Hoc Analysis ◽  
Kaplan Meier ◽  
Safety Outcomes ◽  
Grade 3 ◽  
Post Hoc

524 Background: Lenvatinib (LEN) is approved for first-line treatment of uHCC. Baseline (BL) liver function (Child-Pugh score [CPS] and albumin-bilirubin grade [ALBI]) was prognostic in uHCC patients (pts) who received sorafenib (SOR) but has not been assessed with LEN in uHCC. Here, we report post hoc analysis of BL liver function and efficacy/safety outcomes from the phase 3 REFLECT study. Methods: Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were stratified by BL ALBI or CPS. OS and PFS were estimated by Kaplan–Meier method. Independent radiologic review utilized mRECIST criteria for ORR. Safety was assessed using NCI-CTCAE, version 4.0. Results: Liver function measured by ALBI and CPS seemed to be prognostic for OS and ORR. Median OS was longer in ALBI grade 1 (ALBI-1) vs grade 2 (ALBI-2) pts or for CPS-5 vs CPS-6 on either treatment arm and was longer for LEN vs SOR. ORR was higher in pts with better ALBI or CPS and for LEN vs SOR. Rates of treatment-emergent adverse events grade ≥3 were lower with better BL liver function (ALBI-1 vs ALBI-2: 70% vs 86%; CPS-5 vs CPS-6: 72% vs 86%). Study-drug withdrawal, dose reduction, and dose interruption occurred more often in pts with worse BL liver function. Conclusions: This post hoc analysis suggests ALBI (by OS, PFS and ORR) and CPS (by ORR) may be prognostic in uHCC pts and that BL liver function may be linked with efficacy/safety outcomes. This analysis also found that LEN provided benefit vs SOR for uHCC, regardless of BL liver function. The benefit of LEN may be underestimated, as more ALBI-2 pts and fewer ALBI-1 pts received LEN vs SOR. Clinical trial information: NCT01761266. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document