Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: Results from the randomized phase III CELESTIAL trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 207-207 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Tim Meyer ◽  
Ann-Lii Cheng ◽  
Anthony B. El-Khoueiry ◽  
Lorenza Rimassa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Endpoint ◽  
Systemic Therapy ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 3 ◽  
Advanced Hcc ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

207 Background: C, an inhibitor of MET, VEGFR, and AXL, has previously shown clinical activity in pts with advanced HCC. This phase 3 trial (NCT01908426) evaluated C vs P in previously treated pts with advanced HCC. Methods: In this double-blind, global, phase 3 trial, pts were randomized 2:1 to receive C (60 mg qd) or matched P stratified by disease etiology (HBV, HCV, other), geographic region (Asia, other), and presence of extrahepatic spread and/or macrovascular invasion (EHS/MVI). Eligible pts had pathologic diagnosis of HCC, Child-Pugh score A, ECOG PS ≤1, and must have received prior sorafenib. Pts received up to two lines of prior systemic therapy for HCC and must have progressed following at least one. The primary endpoint was overall survival (OS). Secondary endpoints were investigator-assessed progression-free survival (PFS) and objective response rate (ORR) per RECIST 1.1. The study was designed to detect a hazard ratio (HR) for OS of 0.76 (90% power, 2-sided α = 0.05) at the final analysis with two prespecified interim analyses at 50% and 75% of the planned 621 events. Results: As of 1 Jun 2017, 707 pts were randomized, and 484 deaths had occurred (317 out of 470 for C; 167 out of 237 for P). Baseline characteristics were balanced between the two arms: median age was 64 years, 82% were male, 38% had HBV, 24% had HCV, 25% enrolled in Asia, 78% had EHS, 30% had MVI, 85% had EHS/MVI, and 27% had received two prior systemic therapy regimens for advanced HCC. The study met the primary endpoint at the second planned interim analysis with median OS 10.2 mo for C vs 8.0 mo for P (HR 0.76, 95% CI 0.63-0.92; p = 0.0049). Median PFS was 5.2 mo for C vs 1.9 mo for P (HR 0.44, 95% CI 0.36-0.52; p < 0.001), and ORR was 4% vs 0.4% (p = 0.0086). The most common grade 3/4 adverse events (predominantly grade 3) with higher incidence in the C vs P arm included hand-foot skin reaction (17% vs 0%), hypertension (16% vs 2%), increased aspartate aminotransferase (12% vs 7%), fatigue (10% vs 4%), and diarrhea (10% vs 2%). Conclusion: C significantly improved OS and PFS vs P in previously treated pts with advanced HCC. Adverse events were consistent with the known safety profile of C. Clinical trial information: NCT01908426.

Alpha fetoprotein (AFP) response and efficacy outcomes in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 423-423 ◽  
Author(s):  
Robin Kate Kelley ◽  
Lorenza Rimassa ◽  
Baek-Yeol Ryoo ◽  
Joong-Won Park ◽  
Jean-Frédéric Blanc ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Best Response ◽  
Previously Treated ◽  
Definition Of ◽  
Ecog Ps

423 Background: AFP response, defined as a decrease in serum levels of the tumor marker AFP after therapy, may be associated with improved survival of patients (pts) with HCC treated with locoregional or systemic therapy, and high baseline AFP levels may be associated with poor prognosis. In the phase III CELESTIAL trial (NCT01908426), C, an inhibitor of MET, VEGFR, and AXL, significantly improved overall survival (OS) and progression-free survival (PFS) versus P in pts with previously treated advanced HCC. Here we evaluate clinical outcomes with C in CELESTIAL based on AFP response or progression on treatment. Methods: 707 pts were randomized 2:1 to receive C (60 mg daily) or P. Eligible patients had a pathologic diagnosis of HCC, Child-Pugh score A, and ECOG PS ≤ 1. Pts received prior sorafenib and ≤ 2 lines of prior systemic therapy for HCC. Serum AFP levels were measured centrally at baseline and every 8 weeks thereafter. Outcomes were evaluated for pts with baseline AFP ≥ 20 ng/mL based on AFP response ( ≥ 20% decrease from baseline) or progression ( ≥ 20% increase from baseline) at Week 8. This definition of AFP response has been used in previous studies but requires further validation in large prospective studies. Results: Overall, 331 pts (70%) in the C arm and 160 (68%) in the P arm had baseline AFP ≥ 20 ng/mL; among these pts, 236 (71%) and 111 (69%), respectively, were evaluable for AFP response at week 8. Among evaluable pts, 117 pts (50%) in the C arm vs 14 (13%) in the P arm had an AFP response, and 72 (31%) vs 75 (68%) had AFP progression. Median OS with C was 16.1 mo for pts with an AFP response versus 9.1 mo for pts without a response (HR 0.61, 95% CI 0.45-0.84), and median PFS with C was 7.3 mo versus 4.0 mo (HR 0.55, 95% CI 0.41-0.74). For pts with AFP progression, median OS with C was 8.1 mo, and median PFS with C was 3.6 mo. Hazard ratios for OS and PFS with C also favored AFP responders over non-responders when analyzed using best response through week 24. Conclusions: The AFP response rate was higher with C versus P, and AFP response was associated with longer OS and PFS with C for pts with previously treated advanced HCC. On-treatment AFP changes warrant further evaluation as a biomarker of response. Clinical trial information: NCT01908426.

Impact of lymph node metastases on outcome following treatment with sorafenib in patients with hepatocellular carcinoma (HCC): Subset analysis from the phase III SHARP trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15547-e15547 ◽  
Author(s):  
J. Raoul ◽  
A. Craxi ◽  
C. Porta ◽  
G. Lentini ◽  
A. Nadel ◽  
...  
Keyword(s):  
Lymph Node ◽  
Adverse Events ◽  
Lymph Node Metastases ◽  
Phase Iii ◽  
Advanced Hcc ◽  
Common Grade ◽  
Node Metastases ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Ecog Ps

e15547 Background: Results from the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, a multinational, randomized, placebo-controlled, phase III trial, demonstrated that sorafenib is effective and safe for patients with advanced HCC (Llovet et al, N Engl J Med, 2008). As lymph nodes are among the most common sites of metastasis in patients with HCC, we performed subset analyses to evaluate the efficacy and safety of sorafenib in patients with or without lymph node metastases at baseline. Methods: Patients (N=602) with advanced, unresectable, measurable HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy for HCC were randomized 1:1 to receive either sorafenib 400 mg BID or placebo. End points included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 d from first demonstration of response), time to progression (TTP), and safety. Results: Median TTP, OS, and DCR by subset are shown in the table. The incidence of grade 3/4 drug-related adverse events across subgroups was consistent with that reported for the overall population. The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib prolonged OS and TTP in patients with advanced HCC, whether or not lymph node metastases were present at baseline. The safety profile of sorafenib in patients with lymph node metastases was comparable with that for the overall study population. [Table: see text] [Table: see text]

Paclitaxel Is Safe and Effective in the Treatment of Advanced AIDS-Related Kaposi's Sarcoma

1999 ◽  
Vol 17 (6) ◽  
pp. 1876-1876 ◽  
Author(s):  
Parkash S. Gill ◽  
Anil Tulpule ◽  
Byron M. Espina ◽  
Suzanne Cabriales ◽  
Jocelyn Bresnahan ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Median Duration ◽  
Systemic Therapy ◽  
Kaposi's Sarcoma ◽  
Single Agent ◽  
Kaposi’S Sarcoma ◽  
Duration Of Response ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

PURPOSE: Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. MATERIALS AND METHODS: A regimen of paclitaxel at a dose of 100 mg/m2 was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. RESULTS: Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4+ lymphocyte count was 20 cells/mm3 (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. CONCLUSION: Paclitaxel at 100 mg/m2 given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.

Pembrolizumab (pembro) monotherapy for previously untreated advanced hepatocellular carcinoma (HCC): Phase 2 KEYNOTE-224 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4074-4074
Author(s):  
Jean-Luc Van Laethem ◽  
Ivan Borbath ◽  
Mark Karwal ◽  
Chris Verslype ◽  
Hans Van Vlierberghe ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Response Duration ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 2 ◽  
Open Label ◽  
Advanced Hcc ◽  
Phase 2 Trial ◽  
Recist 1.1 ◽  
Prior Systemic Therapy

4074 Background: Results from cohort 1 of KEYNOTE-224, an open-label, single-arm, multi-country phase 2 trial, demonstrated that pembro monotherapy was efficacious and tolerable in patients (pts) with advanced HCC previously treated with sorafenib. Here, we report results from KEYNOTE-224 cohort 2, which enrolled pts with advanced HCC and no prior systemic therapy. Methods: Eligible pts in cohort 2 had radiologically, histologically, or cytologically confirmed, incurable HCC not amenable or refractory to locoregional therapy, Child Pugh A liver disease, measurable disease based on RECIST 1.1 by blinded independent central review (BICR), ECOG PS 0-1, and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for ̃2 years or until disease progression, unacceptable toxicity, consent withdrawal, or investigator decision. Primary endpoint was ORR (RECIST 1.1 by BICR). Secondary endpoints included DOR, DCR, TTP, PFS, OS, and safety/tolerability. Response was assessed every 9 weeks. Efficacy and safety were assessed in pts who received ≥1 dose of study treatment. DOR was assessed in responders. The estimate and 95% CI of the ORR and DCR were based on the Clopper-Pearson method. Kaplan-Meier method was used to estimate OS, PFS, and DOR. A sample size of ̃50 pts was chosen to provide acceptable precision for the assessment of ORR. Results: Cohort 2 enrolled 51 pts. The median time from the first dose to data cutoff (July 31, 2020) was 21 (range, 17-23) mo. The median age of pts was 68 (range, 41-91) years, one pt was HBV+, 80% had alcohol use, 8% were HCV+, 18% had vascular invasion, 35% had extrahepatic disease, 33% had BCLC Stage B disease, and 67% had BCLC Stage C HCC. ORR was 16% (95% CI, 7-29) and was similar across most subgroups. Median DOR was not reached (range, 3-20+ mo); 70% were estimated to have response duration ≥12 mo. Best overall responses were 0 CR, 8 (16%) PRs, 21 (41%) SDs, and 17 (33%) PDs; response was not evaluable or not assessed for 5 (10%) pts. DCR was 57%. The median TTP was 4 (95% CI, 3-8) mo. The median PFS was 4 (95% CI, 2-6) mo, and median OS was 17 (95% CI, 8-NA) mo. PFS rate at 18 mo was 16%, and OS rate at 18 mo was 46%. Treatment-related AEs (TRAEs) occurred in 27 (53%) pts; the most common TRAEs were diarrhea, fatigue, hypothyroidism, and myalgia. Grade ≥3 TRAEs occurred in 7 (14%) pts. TRAEs led to treatment discontinuation in 6% of pts. Immune-mediated AEs and infusion reactions occurred in 11 (22%) pts. One treatment-related death occurred due to myocarditis, with associated immune-related hepatitis. Conclusions: In pts with advanced HCC and no prior systemic therapy, pembro monotherapy provided durable anti-tumor activity, promising overall survival, and demonstrated a safety profile consistent with that previously observed for pembro in advanced HCC. These findings support further evaluation of pembro-based regimens for the treatment of HCC in the frontline setting. Clinical trial information: NCT02702414.

A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11505-11505
Author(s):  
Brian Andrew Van Tine ◽  
Sant P. Chawla ◽  
Jonathan C. Trent ◽  
Breelyn A. Wilky ◽  
Rashmi Chugh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Synovial Sarcoma ◽  
Primary Endpoint ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Phase 3 ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Trial Information

11505 Background: AL3818 (Catequentinib, Anlotinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 monotherapy in patients (pts) with synovial sarcoma (SS) comparing with dacarbazine in randomization setting. Methods: Patients with a diagnosis of synovial sarcoma requiring second line or further line treatment were eligible for enrollment. The regimen was a 21-day cycle with oral AL3818 administered on 14 days on and 7 days off. This phase 3 trial is randomized in 2:1 ratio of AL3818 comparing to dacarbazine with option of crossover after PD of dacarbazine treatment. Progression free survival (PFS) with Log Rank test is the primary endpoint and this trial for SS is currently completed enrolled in US and Italy. Results: Total 79 pts initiated treatment and are evaluable, 52 received AL3818 as treatment arm (T), and 27 received dacarbazine (D) as control arm (C). Arms T/C median ages were 40.5/42.0 years (range: 18-70+) and 20/16 (38.5%/59.3%) were male. Overall, PFS was 2.89 months (95% CI: 2.73 – 6.87) for AL3818 and 1.64 (95% CI: 1.45 – 2.70) for D. The PFS of study met the primary endpoint with a p-value of 0.0015 and a HR of 0.449 (95% CI: 0.270– 0.744). At the month 4, 6, and 12, the percentages of progression free patients for AL3818 were 48.1%, 42.3% and 26.9%; and for D were 14.85%, 11.1% and 3.7%. For grade 3 treatment-related adverse events, 12(23.1%) of pts experienced for AL3818 and 7(25.9%) of pts experienced for D. The most common AL3818 related grade 3 AEs were diarrhea (5.8%) and hypertension (3.8%). Conclusions: This phase III trial demonstrates improved disease control and superior progression free survival for AL3818 vs dacarbazine in advanced SS. In addition, the study further confirms the acceptable benefit-risk profile of AL3818 from the prior randomized Phase 2b soft tissue sarcoma study (NCT02449343). AL3818 is a meaningful treatment option for pts with advanced SS. Clinical trial information: NCT 03016819 Clinical trial information: NCT03016819.

Effect of macroscopic vascular invasion (MVI), extrahepatic spread (EHS), and ECOG performance status (ECOG PS) on outcome in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib: Analysis of two phase III, randomized, double-blind trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4580-4580 ◽  
Author(s):  
J. Bruix ◽  
A. Cheng ◽  
Y. Kang ◽  
C. Tsao ◽  
S. Qin ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Interest Policy ◽  
Grade 3 ◽  
Ecog Ps

4580^ Background: The landmark phase III SHARP trial (Llovet et al, N Engl J Med, 2008) showed that sorafenib is effective and safe for the treatment of advanced HCC. These results were confirmed in an Asian population in the phase III Asia-Pacific (AP) study (Cheng et al, Lancet Oncol, 2009). We compared outcomes of sorafenib treatment in patients enrolled in the SHARP and AP trials with known baseline predictors of poor prognosis. Methods: Patients with advanced, unresectable, measurable HCC, ECOG PS 0–2, Child-Pugh A, and no prior systemic therapy for HCC were randomized to sorafenib 400 mg BID or placebo (SHARP: N=602; AP: N=226). Patients in the AP study had more evolved disease and a predominance of hepatitis B infection. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 days from first demonstration of response), and safety. Results: Efficacy results are shown in the table . The incidence of grade 3/4 drug-related adverse events (AEs) across subgroups in each study was consistent with the overall population for each study. The most common grade 3/4 AEs in all sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib is effective and safe for the treatment of advanced HCC in patients globally, irrespective of baseline ECOG PS and presence or absence of MVI and/or EHS. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Phase I study of safety, pharmacokinetics, and efficacy of TSU-68 plus S-1 combination in patients with advanced hepatocellular carcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 262-262 ◽  
Author(s):  
Masafumi Ikeda ◽  
Shuichiro Shiina ◽  
Kohei Nakachi ◽  
Shuichi Mitsunaga ◽  
Satoshi Shimizu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Maximum Tolerated Dose ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Treatment Dose ◽  
Pugh Class ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Treatment Safety

262 Background: Sorafenib is the standard chemotherapy for advanced hepatocellular carcinoma (HCC), but its efficacy is limited. TSU-68 is an oral anti-angiogenesis agent that blocks VEGFR-2 and PDGFR. TSU-68 and S-1 have shown favorable efficacy and safety profile for advanced HCC (Kanai et al. 2011; Furuse et al. 2010). This study investigated the safety, tolerability, pharmacokinetics (PK), and efficacy of the TSU-68 plus S-1 combination in patients (pts) with advanced HCC. We also determined the maximum tolerated dose of TSU-68 plus S-1 on the basis of the frequency of associated dose-limiting toxicity (DLT) in this population. Methods: Pts who had not received any prior systemic therapy received 400 mg/day TSU-68 orally and one of the following doses of S-1: 50 mg/m2 (level 0), 80 mg/m2 (level 1), or 100 mg/m2 (level 2). Treatment duration was 4 weeks followed by 2-week rest (A group) or 2 weeks followed by 1-week rest (B group). The starting treatment dose and duration level was 1B, followed by progression to levels 2A and 2B. Treatment safety and tolerability at each level were assessed by enrolling 6 pts according to CTCAE v3.0. Results: Eighteen pts (6 each at levels 1B, 2A, and 2B) were enrolled (age, 58-85 years; male/female, 15/3; HCV/HBV/nBnC, 12/3/4; Child-Pugh class A/B, 18/0). Two pts each at levels 1B (grade 3 gastrointestinal bleeding, grade 2 ascites) and 2A (grade 3 fatigue, grade 3 hand-foot skin reaction) showed DLTs, but no pts at level 2B showed DLTs. The common adverse events were hemoglobin decrease, hypoalbuminemia, and anorexia; these were mild in severity (grade 1-2). PK data from 12 pts at levels 1B and 2A indicated that the area under the curve (AUC) of TSU-68 and 5-FU was unlikely to be affected by TSU-68 plus S-1. Response rate, disease control rate, median time to progression, and median overall survival time were 27.8%, 61.1%, 160 days, and 391 days, respectively. Conclusions: Our findings revealed thatthe TSU-68 plus S-1 combination was well tolerated and had favorable efficacy in patients with advanced HCC, and we recommend treatment with 400 mg/day TSU-68 and 100 mg/m2 S-1 for 4 weeks followed by 2-week rest in these patients. Clinical trial information: Japic CTI-121970.

Outcomes based on age in the phase 3 METEOR trial of cabozantinib (cabo) vs everolimus (eve) in patients with advanced renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4578-4578 ◽  
Author(s):  
Frede Donskov ◽  
Robert J. Motzer ◽  
Eric Voog ◽  
Elizabeth J. Hovey ◽  
Carsten Grüllich ◽  
...  
Keyword(s):  
Adverse Events ◽  
Older Patients ◽  
Objective Response ◽  
Age Groups ◽  
Progression Free Survival ◽  
Phase 3 ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Dose Reductions

4578 Background: The incidence of RCC increases with age with the highest incidence at ~75 years of age (Znaor, Eur Urol 2015). The Phase 3 METEOR trial (NCT01865747) showed a significant improvement in progression-free survival (PFS; HR 0.58, 95% CI 0.45–0.74; P < 0.0001), overall survival (OS; HR 0.66, 95% CI 0.53–0.83, P = 0.0003), and objective response rate (ORR; 17% vs 3%; P < 0.0001) for cabo compared with eve in patients with advanced RCC previously treated with VEGFR TKIs (Choueiri, NEJM 2015, Lancet Oncol 2016). Here we present outcomes by 3 categories of age for the METEOR trial. Methods: 658 patients were randomized 1:1 to cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Endpoints included PFS, OS, and ORR. Subgroup analyses by age ( < 65, 65 to 74, and ≥75 years) are presented. Results: At baseline, 60% of patients were < 65 years old, 31% were 65 to 74 years old, and 10% were ≥75 years old. Subgroups by age generally had similar baseline characteristics in both arms. The HRs for PFS favored cabo for all age groups (HR 0.53, 95% CI 0.41–0.68 for < 65 years old; 0.53, 95% CI 0.37–0.77 for 65 to 74 years old; and 0.38, 95% CI 0.18–0.79 for ≥75 years old). ORR per independent radiology committee for cabo vs eve was 15% vs 5% for < 65 years old, 21% vs 2% for 65 to 74 years old, and 19% vs 0% for ≥75 years old. HRs for OS also favored cabo (HR 0.72, 95% CI 0.54–0.95 for < 65 years old; 0.66, 95% CI 0.44–0.99 for 65 to 74 years old; and 0.57, 95% CI 0.28–1.14 for ≥75 years old). Median OS for cabo vs eve was 21.4 mo vs 17.1 mo for < 65 years old, not reached vs 18.0 mo for 65 to 74 years old, and 18.4 mo vs 14.0 mo for ≥75 years old. Older patients more frequently had dose reductions (60% with cabo and 22% with eve for < 65 years old vs 85% with cabo and 36% with eve for ≥75 years old). Grade 3 or 4 adverse events were generally consistent with the safety profiles in the overall population although some events such as fatigue and hypertension occurred at a higher rate in older patients. Conclusions: Treatment with cabo improved PFS, ORR, and OS compared with eve in patients with advanced RCC irrespective of age. Adverse events in older patients were more frequently managed with dose reductions. Clinical trial information: NCT01865747.

Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: A randomized, placebo-controlled, double-blind, phase III study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4507-4507 ◽  
Author(s):  
Qiu Li ◽  
Shukui Qin ◽  
Shanzhi Gu ◽  
Xiaoming Chen ◽  
Lizhu Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Chinese Patients ◽  
Biological Behavior ◽  
Advanced Hepatocellular Carcinoma ◽  
Double Blind ◽  
Sorafenib Treatment ◽  
Advanced Hcc

4507 Background: Chinese patients (pts) account for more than 50% of hepatocellular carcinoma (HCC) cases in the world and have special features in etiology, biological behavior, treatment strategy and prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib, an inhibitor targeting vascular endothelial growth factor receptor-2, in Chinese pts with pretreated advanced HCC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 trial done in 31 sites in China, pts with HCC who had received at least one line of systemic therapy (including sorafenib and oxaliplatin-based chemotherapy, which is another first-line standard-of-care in China) and had Child-Pugh liver function class A or B ≤7 points were enrolled. The pts were randomly assigned (2:1) to receive 750 mg apatinib orally once daily or placebo and stratified by ECOG performance status (0 or 1), previous sorafenib treatment (yes or no), and extrahepatic spread and/or macrovascular invasion (yes or no) in 28-day treatment cycles. The primary endpoint was overall survival (OS). Results: Between Apr 01, 2014 and May 03, 2017, 393 pts were randomized and received at least one dose of study treatment (261 in apatinib arm and 132 in placebo arm). The median OS was significantly longer with apatinib than that with placebo (8.7 months [95% CI 7.5-9.8] vs 6.8 months [95% CI 5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998]; p=0.0476). Pts in the apatinib arm also had prolonged median progression free survival (PFS) compared with those in the placebo arm (4.5 months [95% CI 3.9-4.7] vs 1.9 months [95% CI 1.9-2.0]; hazard ratio 0.471 [95% CI 0.369-0.601]; p˂0.0001). The objective response rate was 10.7% (95% CI 7.2-15.1) with apatinib versus 1.5% (95% CI 0.2-5.4) with placebo. Treatment-related adverse events (TRAEs) were reported in 250 (97.3%) pts in the apatinib arm and 92 (70.8%) pts in the placebo arm. The most common TRAEs of grade 3 and 4 were hypertension (71 [27.6%] pts in the apatinib arm vs 3 [2.3%] pts in the placebo arm), hand-foot syndrome (46 [17.9%] vs 0), decreased platelet count (34 [13.2%] vs 1 [0.8%]), and decreased neutrophil count (27 [10.5%] vs 0). 24 (9.3%) pts with apatinib and 13 (10.0%) pts with placebo died due to adverse events, and none were deemed treatment-related by investigators. Conclusions: Apatinib significantly prolonged OS and PFS in Chinese pts with pretreated advanced HCC, and was well tolerated with a manageable safety profile. Clinical trial information: NCT02329860 .

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