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  • American Society of Clinical Oncology (ASCO)  (7)
  • 1
    Online Resource
    Online Resource
    Association between overall survival and adverse events with lenvatinib treatment in patients with hepatocellular carcinoma (REFLECT).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 317-317
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 317-317
    Abstract: 317 Background: In the phase 3 REFLECT study, lenvatinib (LEN) demonstrated a treatment effect on overall survival (OS) by statistical confirmation of non-inferiority to sorafenib (SOR) in patients (pts) with unresectable hepatocellular carcinoma (uHCC), who had not received prior treatment for advanced disease (Kudo M et al, Lancet 2018). Lenvatinib is approved in several major markets for the first line systemic treatment of uHCC. The most common adverse events (AEs) in pts treated with LEN were hypertension and diarrhea. In addition, LEN showed a different AE profile from that of SOR. Pts who received LEN experienced more instances of hypertension, proteinuria, dysphonia, and hypothyroidism than patients who received SOR. Recently, hypertension in LEN-treated pts with differentiated thyroid cancer was shown to be correlated with improved efficacy. Here we report the post hoc analysis exploring whether AEs associated with LEN were correlated with longer OS in REFLECT. Methods: 478 Pts were randomized to receive LEN (12 mg/d for actual body weight ≥ 60 kg or 8 mg/d for actual body weight 〈 60 kg). Subgroup analyses were conducted based on whether pts treated with LEN experienced any-grade AEs of interest (AEIs). OS was estimated by the Kaplan-Meier method. Results: The AEIs in pts treated with LEN were hypertension (42%), diarrhea (38%), proteinuria (24%), dysphonia (24%), and hypothyroidism (16%). OS was longer in pts who had several AEs of interest than in those who did not (table). Conclusions: In pts treated with LEN, the occurrence of hypertension, diarrhea, proteinuria, or hypothyroidism was generally associated with longer OS in pts with uHCC in this post hoc exploratory analysis. The potential confounding factors at baseline should be further investigated. Clinical trial information: NCT01761266. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.317
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Transition of the tumor microenvironment with clonal evolution of hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 4_suppl ( 2022-02-01), p. 467-467
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 467-467
    Abstract: 467 Background: The combination of atezolizumab and bevacizumab has become a standard treatment for advanced hepatocellular carcinoma (HCC). The indications for combination immunotherapy, including adjuvant therapy and combination with local therapy, are expected to expand in the future. Although exploring the tumor microenvironment has essential clinical implications in the era of combination immunotherapy, most studies on the tumor microenvironment in HCC are based on the analysis of archival samples at the time of HCC diagnosis. Considering the lengthy clinical course and characteristics of multicentric carcinogenesis, the tumor microenvironment may not be constant, but may differ from that at the time of advanced HCC. The present study aimed to assess the changes in the tumor microenvironment during the evolution to advanced HCC using archival samples and samples obtained prior to systemic therapy from the same patients. Methods: The tumor microenvironment was compared in 20 cases by immunohistochemical analyses of CD8, PD-L1, and VEGF expression. Levels of CD8-positive lymphocytes were defined as the mean number of CD8-positive lymphocytes in the tumor per 1 mm 2 and classified as low or high infiltration using the median value. PD-L1 expression was classified as negative ( 〈 1%) or positive (≥1%). VEGF expression was classified as low ( 〈 50%) or high (≥50%). Of the 20 cases, gene expression analysis was performed by the PanCancer IO360 Panel in 14 cases. Results: Approximately 40% of the archived samples were obtained at the early stage. Comparison of the tumor microenvironment between the two time points showed that 35% of the patients changed to CD8-positive lymphocyte high infiltration, 20% to positive PD-L1 expression, and 29% to high VEGF expression. The result of comparing gene profile was different between the archival samples and those prior to systemic therapy in 64% of the patients on the expression heat map. Gene set enrichment analysis showed significant changes in T cell cytotoxicity between the two time points. Conclusions: The tumor microenvironment might not be constant, but may change during the evolution to advanced HCC. In the present study, based on the results of the gene mutation analysis using whole-exome sequencing, we also reported the analyses by carcinogenic patterns such as multicentric occurrence and intrahepatic metastasis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.4_suppl.467
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Real-world data in 1000 patients with unresectable hepatocellular carcinoma (HCC) treated with systemic therapy: Patient background in PRISM study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 566-566
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 566-566
    Abstract: 566 Background: Systemic therapy is one of the most important treatment modalities for unresectable hepatocellular carcinoma (HCC). At present, six regimens, except durvalumab plus tremelimumab, are reimbursable for the treatment of HCC in Japan. In clinical practice, there are various patient backgrounds and patterns in the treatment sequence of systemic therapy. Therefore, a prospective, observational, large-scale multicenter study of systemic therapy for HCC (PRISM) was conducted to establish real-world evidence from real-world data in Japan. Methods: Patients with histologically or clinically diagnosed HCC, with no prior systemic therapy, with written informed consent were consecutively enrolled into the study. The primary endpoint is overall survival, and the secondary endpoints are the progression-free survival, time-to-treatment failure, grade 3-4 adverse events, and proportion of transition to subsequent treatment; all endpoints are calculated by each regimen/treatment line. The planned sample size is 1,000 patients with an enrollment and follow-up period of 2 years each. Clinical trial registration: UMIN000040488. Results: From August 2020 to July 2022, the enrollment of 1,000 patients was completed in 42 participant hospitals in Japan. As of Sep 2022, the 1000 patients’ background data have been collected. The median age with range was 73 years (30-93). ECOG performance status was 0 in 612 patients (77.9%), and Child-Pugh score was 5 points in 358 (50.2%) and 6 in 226 (31.7%). BCLC stage was B in 277 patients (36.9%) and C in 391 patients (52.1%). 210 patients (26.8 %) and 207 patients (26.4%) had portal vein tumor thrombosis and extrahepatic metastasis, respectively. The median AFP level was 33 ng/mL (range: 1.1- 524878.9). As first-line therapy, atezolizumab plus bevacizumab was selected in 650 (82.5%), lenvatinib in 116 (14.7%), and sorafenib in 15 (1.9%) patients. Conclusions: The analysis of these real-world data of systemic therapy for patients with unresectable HCC could help clarify the treatment outcomes in clinical practice, and is expected to be broadly applicable to real-world evidence in all Japan. Clinical trial information: UMIN000040488 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.566
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Approaching the tumor microenvironment in patients with advanced hepatocellular carcinoma using needle biopsy samples.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 3_suppl ( 2021-01-20), p. 334-334
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 3_suppl ( 2021-01-20), p. 334-334
    Abstract: 334 Background: Currently, combined immunotherapy of atezolizumab (anti-PD-L1 antibody) plus bevacizumab (a humanized anti-VEGF monoclonal antibody) is the standard first-line treatment in patients with advanced hepatocellular carcinoma (HCC). At the threshold of this new era, there is limited information about tumor microenvironment (TME) in advanced HCC. Several studies on TME in HCC have analyzed samples obtained via hepatic resection. In general, hepatic resection is indicated for patients with limited size and number of intrahepatic nodules, i.e., early stage HCC. In contrast, most patients who have an indication for systemic therapy have developed macroscopic vascular invasion (MVI) or/and extrahepatic metastasis, namely in advanced stage HCC. Progression from an early stage HCC to an advanced stage HCC involves a lengthy clinical course, therefore, the TME at the time of initial diagnosis may differ from that at the time of systemic therapy indication. The present study was aimed to analyze the TME by using needle biopsy samples obtained prior to initiation of systemic therapy in patients with advanced HCC. Methods: Between March 2019 and May 2020, 80 patients underwent liver tumor biopsy at the time of indication for systemic chemotherapy. HCC was confirmed via pathological examination in 70 patients and their samples were analyzed. Microsatellite instability (MSI) was evaluated using polymerase chain reaction. Programed death-ligand 1 (PD-L1) expression and the levels of tumor-infiltrating lymphocytes (TIL) were evaluated using immunohistochemical staining. PD-L1 expression was defined as per the tumor proportion score (TPS; the number of PD-L1-positive cells/total number of tumor cells) and was classified as low (TPS 〈 1%) or high (TPS 〉 1%). Levels of TIL were defined as the mean number of CD8-positive lymphocytes in the tumor per 1 mm 2 and classified as low or high using the median value. Results: Out of the 70 tumors, one was MSI-high and 69 were MSI-negative. The PD-L1 expression was 〈 1% in 50 samples, 1%–10% in 12, 11%–20% in 7, and 21%–30% in 1. The median level of TIL was 266/mm 2 . PD-L1 high TIL high was present in 20.0%, PD-L1 low TIL low in 38.5%, PD-L1 high TIL low in 8.6%, and PD-L1 low TIL high in 32.9%. In the MSI-high tumor, PD-L1 expression was 〈 1% and the level of TIL was 142/mm 2 . High PD-L1 expression and high levels of TIL were associated with hepatitis C virus infection, high alpha-fetoprotein levels, and presence of MVI respectively. We are currently performing RNA-sequencing in order to obtain more details about TME in patients with advanced HCC. Conclusions: MSI-high advanced HCC was detected in 1.4% patients and was not necessarily associated with a “hot” immune microenvironment. PD-L1 expression and levels of TIL were associated with some clinical parameters. In the present study, we also reported the changes in the TME over time.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.3_suppl.334
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 5
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    REPLACEMENT trial in progress: Combination therapy with atezolizumab plus bevacizumab for TACE unsuitable patients with beyond up-to-seven criteria in intermediate stage hepatocellular carcinoma: A phase II study.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS4162-TPS4162
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS4162-TPS4162
    Abstract: TPS4162 Background: Transarterial chemoembolization (TACE) had been developed as a standard of care in patients with intermediate-stage HCC at a time when systemic therapy was not available. This stage includes a certain TACE-unsuitable subpopulation, such as beyond up-to-seven criteria. Recently, the American Association for the Study of Liver Diseases and Asia-Pacific Primary Liver Cancer Expert Meeting have recommended systemic therapy for those patients to achieve overall survival (OS) beyond 2 years without impaired liver function in their consensus guideline. However, there is not enough data on systemic therapy for this population. Atezolizumab (Atezo), anti-PD-L1 antibody, plus Bevacizumab (Bev), anti-VEGF antibody, combination therapy has been shown to significantly improve OS, progression-free survival (PFS), and overall response rate (ORR) against sorafenib, which is a standard of care in unresectable HCC according to a phase III randomized controlled trial, IMbrave150. Therefore, we investigate the efficacy and safety of Atezo+Bev combination therapy in patients with HCC beyond up-to-seven criteria in this trial. Methods: REPLACEMENT trial is a multicenter, single-arm phase II study of Atezo+Bev combination therapy. Key eligibility criteria are age ≥20 years, ECOG performance status 0-1, Child-Pugh A, no vascular invasion, no extrahepatic metastasis, beyond up-to-seven criteria, and patients who have received neither systemic therapy nor TACE. Patients will be administrated Atezo 1200 mg/body + Bev 15 mg/kg once every 3 weeks. The primary endpoint is PFS per modified RECIST (mRECIST). The secondary endpoints include PFS, ORR, duration of response (DOR) per mRECIST; PFS, ORR, DOR per RECIST ver.1.1; OS and safety including change of liver function based on albumin-bilirubin (ALBI) score until disease progression. A total of 60 events are necessary to investigate the hypothesis that a target point estimation of PFS rate at 6 months (null population: 55%, alternative population: 73%). The estimated sample size is, therefore, 70 patients. In addition, the results of the Atezo+Bev therapy in this arm will be compared with those in approximately 600 TACE treated consecutive patients with intermediate-stage HCC, using the propensity score matching method, as an exploratory analysis of a possible replacement of TACE by the Atezo+Bev therapy. Patients’ enrollment had already started in December 2020, and 12 patients were enrolled as of 16th February ’21. Clinical trial information: jRCTs071200051.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.TPS4162
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 6
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    Phase I study of safety, pharmacokinetics, and efficacy of TSU-68 plus S-1 combination in patients with advanced hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 262-262
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 262-262
    Abstract: 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/m 2 (level 0), 80 mg/m 2 (level 1), or 100 mg/m 2 (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/m 2 S-1 for 4 weeks followed by 2-week rest in these patients. Clinical trial information: Japic CTI-121970.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.262
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Primary analysis of a phase II study of atezolizumab plus bevacizumab for TACE-unsuitable patients with tumor burden beyond up-to-seven criteria in intermediate-stage hepatocellular carcinoma: REPLACEMENT study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 4125-4125
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4125-4125
    Abstract: 4125 Background: Intermediate-stage hepatocellular carcinoma (HCC) is a heterogeneous disease; therefore, the efficacy of transarterial chemoembolization (TACE) is affected by tumor burden, resulting in a wide range of survival outcomes. Multiple recent guidelines suggest that systemic therapy is preferable for patients with intermediate-stage HCC who are TACE unsuitable because of high tumor burden, such as beyond up-to-seven criteria. The Phase III IMbrave150 study established atezolizumab plus bevacizumab (atezo+bev) as the standard of care in patients with unresectable HCC. Here, we investigated whether atezo+bev is potentially superior to TACE in efficacy and safety in TACE-naïve patients with unresectable intermediate-stage HCC beyond up-to-seven criteria. Methods: In this multicenter, phase II study, atezo 1200 mg + bev 15 mg/kg q3w were administered to eligible patients (as defined above plus having Child-Pugh A liver function) enrolled from Dec 2020 to Sep 2021 until discontinuation due to disease progression, adverse events (AEs), or other reasons. Overall survival (OS) follow-up continued for 2.5 years after enrolment. The primary endpoint was progression-free survival (PFS) assessed by mRECIST by investigator; secondary endpoints were objective response rate (ORR), PFS by RECIST v1.1, OS, and safety. In an exploratory analysis, we conducted propensity score matching (PSM) analysis to compare the efficacy between atezo+bev and TACE, the data of which were retrospectively collected in patients treated with TACE in each participating center from Jan 2017 to Dec 2017. Results: In total, 74 patients were enrolled (male, 87.8%; mean age, 73.7 years; median [range］maximum tumor diameter by pre-treatment CT, 4.8［1.0,13.0］cm). Median (min, max) follow-up was 15.0 (1.6, 21.6) months. Median PFS was 9.1 (95%CI: 7.1, 10.2) months (by mRECIST; primary endpoint). ORR was 45.9 (95%CI: 34.3, 57.9) % by mRECIST. Median OS was not reached (NR) (95%CI: NR, NR). 12-month OS rate was 84.6 [95%CI: 74.0, 91.2]%. The most frequent AEs (any grade ≥10% of patients) were hypertension, proteinuria, malaise, anorexia, edema, pruritis, and diarrhea. Conclusions: Atezo+bev provides clinical benefits to TACE-unsuitable patients with intermediate-stage HCC beyond up-to-seven criteria. Results of the exploratory PSM analysis will be presented. Clinical trial information: jrcts071200051 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.4125
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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