bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C).
Authors: Noronha Vanita , Joshi Amit , Patil Vijay Maruti , Chougule Anuradha , Mahajan Abhishek , Janu Amit , Purandare Nilendu , Kumar Rajiv , More Sucheta , Goud Supriya , Kadam Nandkumar , Daware Nilesh , Shah Srushti , Yadav Akanksha , Dutt Amit , Trivedi Vaishakhi , Behel Vichitra , Banavali Shripad Dinanath , Prabhash Kumar 
Published: March 2020

9001 Background: Standard first-line therapy for EGFR mutant advanced non-small cell lung cancer (NSCLC) is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI would improve outcomes. Methods: Phase III randomized trial in advanced chemotherapy-naïve NSCLC harboring EGFR sensitizing mutation (exon 19, 21 or 18) with performance status (PS) 0 to 2 planned for palliative therapy. Patients were stratified for PS and EGFR mutation and randomly assigned (computer-generated randomization by independent biostatistician) 1:1 to gefitinib 250 mg orally daily (gef) or gefitinib 250 mg orally daily with pemetrexed 500 mg/m2 IV and carboplatin AUC 5 IV every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m2 IV every 3 weeks (gef+C). Restaging was every 2 to 3 mths; therapy continued until progression or intolerable toxicity. Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), toxicity and response rate. Survival endpoints were assessed in the intention-to-treat population. Results: Between Aug 2016 and Aug 2018, 350 patients were randomly assigned to gef (n = 177) and gef+C (n = 173). Median age was 54 yrs, 48% were females, 84% never-smokers, 21% were PS 2 and 18% had brain metastases. Median follow-up in surviving patients was 17 months (range, 7 to 30). Radiologic response rates were 81% and 69% in gef+C and gef respectively, P = 0.012. 234 patients (67%) have had events for PFS, 98 in gef+C and 136 in gef. Estimated median PFS was significantly longer with gef+C than gef (16 months, [95% CI, 13.7 to 18.3] vs. 8 months [95% CI, 7.1 to 8.9]; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39 to 0.65; P < 0.001). 120 patients (34%) have died, 42 in gef+C and 78 in gef. Estimated median OS was significantly longer with gef+C than gef (not reached vs. 18 months [95% CI, 14.28 to 21.72]; hazard ratio for death, 0.45; 95% CI, 0.31 to 0.66; P < 0.001). Clinically relevant ≥ grade 3 toxicities occurred in 51% and 25% of patients in gef+C and gef arms respectively, P < 0.001. Conclusion: Adding pemetrexed-carboplatin chemotherapy to gefitinib significantly prolonged progression free and overall survival but also increased toxicity. Pemetrexed-carboplatin-gefitinib represents a new standard first-line therapy for EGFR mutant NSCLC. Clinical trial information: CTRI/2016/08/007149.
A phase I study to evaluate safety, tolerability, pharmacokinetics and antineoplastic activity of BPI-7711 in patients with EGFR/T790M mutation advanced or recurrent NSCLC.
Authors: Shi Yuankai , Fang Jian , Shu Yongqian , Wang Donglin , Yu Huiqing , Zhao Yanqiu , Zhang Liangming , Zhu Bo , Li Xingya , Chen Gongyan , Shi Jianhua , Zheng Rongsheng , Huang Jian'An , Yang Sheng , Long Jieran , Gao Wen , Greco Michael , Wang Jing , Li Xiao 
Published: March 2020

9034 Background: BPI-7711 is a 3rd generation irreversible EGFR-TKI that is selectively against EGFR TKI–sensitizing mutations and the T790M resistance mutations. We are conducting a phase I study to determine the safety and efficacy of BPI-7711 in patients with advanced or recurrent EGFRm+/T790M+ NSCLC. Methods: NSCLC patients who had documented disease progression after 1st/2nd generation EGFR-TKI treatment and with EGFRm+/T790M+ confirmed by central lab were enrolled in the multicenter trial (NCT03386955) into “3+3” dose escalation or expansion cohorts. BPI-7711 was orally administered at doses of 30~240 mg in capsules. Patients in dose-escalation cohorts firstly received a single dose of BPI-7711 followed by a 7-day pharmacokinetic (PK) evaluation period then received the same dose daily until disease progression or intolerable toxicity(ies) per CTCAE V4.03. Treatment efficacy per RECIST 1.1 was evaluated every 6 weeks since daily treatment commence. Once efficacy was observed in a dose, its expansion cohort was opened to enroll patients for daily treatment. Results: As of 23 December 2018, 82 patients (median age 55, 27 males, 55 females) were enrolled into 5 dose escalation cohorts (30/60/120/180/240 mg) and 4 dose expansion cohorts (30/60/120/180 mg). No DLT was observed and MTD was not reached. For all safety-evaluable patients, most common treatment emergent adverse events (TEAEs) (≥10%) were white blood cell count decreased (21.3%), neutrophil count decreased (17.3%), upper respiratory tract infection (17.3%), vomiting (12.0%) and diarrhea (10.7%), and all were Grade 1 or 2. Grade 3~4 TEAEs were occurred in 8.0% patients and 4.0% of them were treatment-related per investigators’ judgement. SAEs were reported in 4.0% of patients, and 1.3% were treatment-related. For all efficacy-evaluable patients, the overall ORR of all doses was 54.5% (30/55) including 1.8% CR and 52.7% PR. The disease control rate (DCR) was 96.4%. For patients in 120/180 mg cohorts, the ORR was 64.1% (25/39) and DCR was 97.4%. PK analyses showed BPI-7711 exposure increased in a dose-proportional manner from 30 to 180 mg after single and multiple doses. Conclusions: BPI-7711 was well tolerated and highly effective in acquired T790M+ NSCLC patients. Phase II trials are under preparation. Clinical trial information: NCT03386955.
The efficacy of immune checkpoint inhibitors and PD-L1 status in patients with advanced non-small cell lung cancer harboring oncogenic driver alterations: Immuno-oncology biomarker study in LC-SCRUM-Japan.
Authors: Yoh Kiyotaka , Matsumoto Shingo , Kunimasa Kei , Kodani Masahiro , Nishi Koichi , Nakagawa Taku , Sugawara Shunichi , Kato Tomohiro , Sakakibara-Konishi Jun , Hayashi Yuichiro , Tsuta Koji , Motoi Noriko , Ishii Genichiro , Goto Koichi 
Published: March 2020

9046 Background: The efficacy of immune checkpoint inhibitors (ICI) and PD-L1 status in patients with advanced non-small cell lung cancer (NSCLC) harboring oncogenic alterations has not been fully investigated. We initiated this immuno-oncology biomarker study as part of nationwide genomic screening by LC-SCRUM-Japan (LC-SCRUM-IBIS). Methods: Lung cancer patients enrolled in LC-SCRUM-IBIS underwent targeted next-generation sequencing (NGS) with Oncomine Comprehensive Assay, PD-L1 immunohistochemistry (IHC) assays and further whole-exome sequencing (WES) to determine tumor mutation burden. According to subtype of oncogenic alterations, the efficacy of ICI and PD-L1 status were analyzed. Results: Between Feb 2017 and May 2018, 1017 lung cancer patients were enrolled. Of these, 832 NSCLC patients had adequate tumor samples and were included in this analysis. Targeted NGS showed that major oncogenic alterations included 157 EGFR, 83 KRAS, 33 MET, 30 HER2, 25 FGFR, 22 PIK3CA, 19 ALK, 15 ROS1, 10 RET, 5 BRAF and 13 others. High expression of PD-L1 ( > 50% of tumor cells by 22C3) were observed in RET (70%), MET (67%), ROS1 (53%), KRAS (41%) and BRAF (40%) positive tumors. One-hundred five patients were evaluable for the efficacy of ICI, including 80 non-squamous and 25 squamous histology. Among them, 104 were treated with PD-1/PD-L1 monotherapy and only 1 in combination therapy of ICI. Median treatment line was 2 (range, 1-9). The response rate was 19% (20/105) and median progression-free survival (PFS) and overall survival (OS) were 3.3 and 18.3 months. In 50 patients harboring at least one oncogenic alterations, the response rate, PFS and OS were 18% (9/50), 3.3 and 24.8 months. Among 9 responders to ICI, 3 had KRAS, 2 had MET and 1 each had ALK/EGFR/HER2/RET. Six (26%) of 23 patients with both high PD-L1 expression and at least one oncogenic alterations responded to ICI. Conclusions: PD-L1 status seemed to vary among patients with advanced NSCLC harboring oncogenic alterations. New biomarker for ICI therapy in this population should be moreover explored. Updated results on WES analysis will be presented at the meeting.
Clinical outcomes of EGFR+ NSCLC pts treated with immune checkpoint inhibitors (ICI).
Authors: Piotrowska Zofia , Cobb Rosemary G. , Banwait Mandeep , Marcoux Nicolas , Mooradian Meghan , Dagogo-Jack Ibiayi , Lin Jessica Jiyeong , Heist Rebecca Suk , Shaw Alice Tsang , Gainor Justin F. , Sequist Lecia V. 
Published: March 2020

9069 Background: ICIs have limited efficacy in EGFR+ NSCLC with ORR ~10% if PDL1 > 25% in ATLANTIC, yet ICIs are often used in later lines of therapy as pts and providers feel there may be little risk. The impacts of ICI in this setting are poorly understood. We describe our institutional experience of ICI use in EGFR+ NSCLC. Methods: MGH pts with advanced EGFR+ NSCLC treated with ICI (any line) were retrospectively reviewed for demographics, PDL1, treatment duration and patient outcomes. Disease flare was defined as hospital/hospice admission due to progression or death (Chaft CCR 2011) within 30d of ICI. Results: 40 pts with EGFR+ NSCLC (22 del19, 11 L858R, 5 ins20, 2 other) received ICI between 7/2012-12/2018. 13 were on a clinical trial. 4 had SCLC transformation. Median # of prior therapies = 3 (range, 0-8). Of 16 with PDL1 quantified, 8 had PDL1 > 25%. ICI regimens were: nivolumab (nivo; n = 16), pembrolizumab (pembro; 9), atezolizumab (atezo; 3), ipilimumab/nivo (7), carboplatin/pemetrexed (pem)/pembro (3), pem/pembro (1), paclitaxel/atezo (1). 18 pts stopped TKI ≤21d prior to ICI start. Median duration of treatment (DOT) was 25 days (range, 1-1482). DOT was > 1 yr for 2 pts (5%), treated with 1st-line nivo/erlotinib (erlo) and 3rd-line nivo. All 8 pts with PDL1 > 25% had DOT < 2 mos. Disease flare within 30d of ICI occurred in 16/40 (40%) overall, 8/18 (44%) who stopped TKI ≤21d of ICI start, and 14/26 (54%) who received ICI in 4thline or later. 8 pts had concurrent TKIs (4 erlo/nivo, 2 erlo/pembro, 1 erlo/atezo, 1 osimertinib (osi)/nivo); 3/8 discontinued ICI for toxicity (all 3 treated first-line). 5 pts received osi immediately post-ICI. There was no pneumonitis on osi post-ICI; 1 pt developed gr3 LFTs and gr4 hypoNa. Conclusions: In this real world cohort of EGFR+ NSCLC, clinical benefit from ICI (assessed by DOT) was rare, including pts with high PDL1. 5% had durable benefit (both pts received ICI in earlier lines of therapy). A previously underappreciated negative outcome of ICI is that admission to hospital, hospice or death within 30d of ICI occur in up to 54% pts. This may be related to disease flare or hyperprogression and suggests that use of ICI in heavily pretreated EGFR+ NSCLC may negatively impact outcomes at end-of-life and should be used with caution.
Osimertinib with chemotherapy for EGFR-mutant NSCLC at progression: Safety profile and survival analysis.
Authors: Neal Joel W. , Hausrath Daniel , Wakelee Heather A. , Cunanan Kristen , Liu Stephen V. , Banwait Mandeep , Sequist Lecia V. , Stirling Kevin , Piotrowska Zofia 
Published: March 2020

9083 Background: First generation EGFR TKIs are well tolerated with chemotherapy (chemo), and have evidence of improved efficacy in EGFR-mutant NSCLC. Osimertinib (osi) is a 3rd-generation EGFR TKI with improved T790M and CNS activity. Safety and outcome data combining osi and concurrent chemo are limited. Methods: EGFR-mutant pts who received osi with chemo between 12/2015 and 8/2018 were retrospectively identified at two institutions. Pt demographics, toxicities and outcomes were collected by chart review. Results: 35 pts received osi + chemo, 29/35 pts had CNS mets. 16/35 had > = one prior chemo and/or immunotherapy, 34/35 previously received a 1st/2nd gen EGFR TKI (25/35 T790M+ at progression), and all 35 had prior progression on osi. 47 osi + chemo regimens were abstracted: carboplatin/pemetrexed+/-bevacizumab (n = 17), cisplatin/pem (1), carbo/taxane (2), pem+/-bev (7), taxane (7), gemcitabine (8), irinotecan (3), vinorelbine (2); 32/35 pts had platinum. Osi was dosed at 80 mg QD (32), 160 mg QD (2), or 80mg QOD (1). Toxicities (table) occasionally led to treatment delay (n = 5), osi dose-reduction (2) and discontinuation (3). Median overall survival (mOS) from metastatic diagnosis was 48.4 mo (95% CI 30.7-NR); mOS from first osi was 19.6 mo (95% CI 16.1-32.6). Median duration of treatment (mDOT) for first regimen of chemo + osi was 5.3 mo (95% CI 4.1-9.5); stratifying by chemo, mDOT for platinum doublet + osi was 6.1 mo (95% CI 4.7-NR) and mDOT for osi + single agent was 3.2 mo (95% CI 2.4-5.3). In the 29 pts with brain mets receiving their first regimen of osi + chemo, 6 had CNS progression but only 2 required radiation at progression. Conclusions: Osimertinib is tolerable in combination with many standard chemo regimens for EGFR-mutant NSCLC. mDOT for platinum doublet and single agent are similar to historical controls, but CNS disease control appears better than expected for chemotherapy alone. Adding chemotherapy at the time of progression on osimertinib may be considered for selected pts, particularly those with known CNS mets. [Table: see text]
Cancer cachexia, sarcopenia and hand-GRIP strength (HGS) in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): A prospective, observational study.
Authors: Agelaki Sofia , Rounis Konstantinos , Papadaki Chara , Monastirioti Alexia A , Vamvakas Lampros , Gioulbasanis Ioannis , Mavroudis Dimitrios , Makrakis Dimitris A 
Published: March 2020

9099 Background: Cancer cachexia syndrome, affecting up to 80% of patients (pts) with NSCLC, is characterized by systemic inflammation, negative protein and energy balance and poor patient outcome. HGS has been independently correlated with outcome in pts with advanced cancer. We investigated the potential association between cachexia, sarcopenia and HGS with outcome in pts with advanced NSCLC treated with ICIs. Methods: Fifty-five pts with NSCLC treated with ICIs were included in the analysis. Patient and disease characteristics and data on outcome measures were prospectively collected. Cancer cachexia was defined as weight loss > 5% in the last 6 months, BMI < 20% (or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia) and any degree of weight loss > 2%. Baseline HGS was measured using the JAMAR analogue dynamometer. Results: Median age was 69 years, 50% of pts had non-squamous histology, 69% had PS 0-1, 61% had cancer cachexia and mean HGS was 27 kgs. Partial response, stable disease and progressive disease was recorded in 16%, 33% and 51% of pts, respectively. Median PFS was 4 months and median OS was 7.8 months. There was no association of cachexia or HGS with tumor burden, number of metastatic sites, LDH or neutrophil/lymphocyte ratio. Cachexia had a negative impact on HGS (p = 0,001). Pts with cachexia had lower response rates (4% vs 37%, p = 0.002), disease stabilization rates (32% vs 81%, p = 0.003) and shorter PFS (3.7 vs 8.2 months, p = 0.008) compared to non-cachectic pts. In multivariate analysis, cachexia independently predicted for shorter PFS (HR = 2.7, CI: 1.15 – 6.46, p = 0.023). Data on sarcopenia are being analyzed and will be presented at the meeting. Conclusions: Cancer cachexia is associated with lower response rates and disease stabilization rates and independently predicts for shorter PFS in pts with NSCLC treated with ICIs. To our knowledge this is the first report demonstrating a between the host’s immune and metabolic responses. The study of cancer cachexia may offer a new platform for the development of novel biomarkers of resistance to ICIs.
The effect of eltrombopag in managing thrombocytopenia associated with tyrosine kinase therapy in patients with chronic myeloid leukemia and myelofibrosis.
Authors: Shoukier Mahran , Kantarjian Hagop M. , Cortes Jorge E. , Jabbour Elias , Ravandi Farhad , Garcia-Manero Guillermo , Kadia Tapan M. , Matthews Jairo , Verstovsek Srdan , Borthakur Gautam 
Published: March 2020

e18539 Background: Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic phase (CP) chronic myeloid leukemia (CML). Up to have patients with CML may develop grade ≥3 thrombocytopenia, leading to treatment interruptions and dose reductions. Similarly, management of thrombocytopenia in myelofibrosis (MF) can be challenging because the condition may result in dose adjustments and interruptions of ruxolitinib. Methods: We conducted a non-randomized, phase II, single-arm study to determine the efficacy of eltrombopag for patients with CML or MF with persistent thrombocytopenia during therapy with a TKI or ruxoltinib. We enrolled 15 CML patients with persistent grade ≥3 thrombocytopenia (platelets ≤50 x 109/l) and six MF patients with platelets < 100 x 109/l after at least 3 months of therapy with a TKI or ruxolitinib. Patients received eltrombopag at a starting dose of 50 mg daily, with dose escalation to a maximum of 300 mg daily according to platelet response. Patients were followed with a weekly complete blood count until a stable platelet count was achieved. The target response was a complete response, defined as a platelet count ≥50 x 109/l for CML and ≥100 x 109/l for MF in at least 30% of subjects, sustained for 3 months while continuing TKIs or ruxolitinib therapy. Results: We enrolled 21 patients (CML = 15, MF = 6), with a median age of 60 years (range, 31-99 years). The median platelet count was 44 (range, 3-49) in patients with CML and 62 (range, 25-91) in those with MF. After a median duration of treatment of 18 months (range, 5-77 months), 11 of the 15 patients with CML achieved a complete platelet response at eltrombopag doses of 50–300 mg per day. The median peak platelet count among responders was 133 (range, 6-1225) x 109/l. Nine patients with CML experienced an improvement in cytogenetic response. In 5 patients with CML, the TKIs dose was increased and maintained while continuing eltrombopag. None of the 5 patients with MF had a sustained increase in platelet count to ≥100 x 109/l. No progression of disease was documented in any patient. Therapy was generally well tolerated. One patient (CML) discontinued therapy secondary to toxicity (persistent transaminitis with an accompanying lack of response). Conclusions: Eltrombopag demonstrated clinical efficacy in some patients with CML who were treated with TKIs. No similar benefit was observed in patients with MF who were treated with ruxolitinib. Eltrombopag might be a useful adjunct for patients with CML experiencing persistent thrombocytopenia. Clinical trial information: NCT01428635.
Feasibility of brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in children and adolescents (< 18 years) with early relapse Hodgkin lymphoma.
Authors: Fernandez Karen S. , Mavers Melissa , Chang-Halpenny Christine N. , Titapiwatanakun Ruetima , Baker Katherine , Pugmire Brian , Tcheng Wendy , Agarwal-Hashmi Rajni 
Published: March 2020

e19012 Background: High-dose therapy followed by autologous stem-cell transplantation (ASCT) is standard of care for patients with relapsed Hodgkin lymphoma (HL). Approximately 50% of relapsed HL patients are cured after ASCT. However, most patients with unfavorable risk factors (refractory disease, early relapse < 12 months and extranodal involvement prior to ASCT) progress after ASCT. Brentuximab Vedotin (BV) improves progression-free survival (PFS) when given as early consolidation after ASCT in adults. In pediatrics, the use of consolidative BV for relapsed HL has not been studied. Methods: Retrospective review of relapsed HL patients who received post ASCT consolidative BV from January 2016 to January 2017. We evaluated time of relapse, sites of involvement, presence of extranodal disease, clinical response after salvage therapy, response, PFS and BV toxicity. Results: During the study period 6 patients (age 12 -18 years) had relapsed HL. Of those, five had high risk (IIIB n = 1 , IVA n = 2, IVB n = 2) and one intermediate risk (IIA) disease. All had disease progression 0 – 3 months after completion of frontline therapy. High risk patients received ABVE-PC regimen and intermediate risk received Stanford V. Four patients received radiation therapy (RT) based on anatomical response as per protocol. Following relapse, 2 cycles of salvage Gemcitabine and Vinorelbine was given to 5 patients. Due to partial response, two of these patients received 2 additional cycles of BV-Bendamustine. One patient was re-induced with BV-Gemcitabine. FDG-PET/CT status prior to ASCT was negative for all 6 patients (Deauville score equal to or less than 3). High dose therapy prior to ASCT consisted of BEAM or BEC. Four patients received additional RT. All patients received consolidative BV every 3 weeks up to 16 cycles. Two patients experienced grade 3 motor and sensorial neuropathy and discontinued BV after 12 cycles. Two patients experienced grade 3 neutropenia. At present the PFS for the six patients is 12, 16, 23, 24, 28 and 30 months. Conclusions: Early consolidation with BV after ASCT is feasible in patients less than 18 years of age. Toxicity included grade 3 peripheral neuropathy and neutropenia. Larger studies are needed to determined safety and efficacy of consolidative BV post ASCT.
A phase I/II study of the anti-programmed cell death-1 (PD-1) antibody AK105 in patients with relapsed or refractory classic Hodgkin lymphoma (cHL).
Authors: Song Yuqin , Zhu Jun , Lin Ningjing , Zhang Chen , Jin Xiaoping , Xu Shuping , Li Baiyong , Xia Yu 
Published: March 2020

e19017 Background: AK105 is a humanized IgG1 mAb that blocks PD-1 binding to PD-L1 allowing T-cells to recognize and kill tumor cells. Key attributes of AK105 include antibody engineering to eliminate Fc mediated effector function, and a slower off-rate on antigen binding resulting in improved receptor occupancy. These features were designed to offer more robust biological effect and enhance anti-tumor activity of AK105. Methods: A multicenter, Phase I/II, single-arm study in relapsed/refractory cHL (NCT03722147) began in July, 2018, evaluating the safety and efficacy of AK105 administered IV q2w till disease progression (response assessed by Lugano 2014 criteria). Eligible pts had relapsed/refractory cHL after most recent therapy with progression after autologous hematopoietic stem cell transplantation, or at least 2 lines of prior chemotherapy. Enrollment for Phase I part of the study was completed, and Phase II at the RP2D of AK105 200 mg q2w is ongoing. Results: As of 1 Feb, 2019, in the Phase I part, 6 Chinese patients (pts) median age 26.5 years [19–38], female 33%, ECOG 0/1 ([67%/33%]), had received a median of 7 (3–12) doses of AK105 200mg q2w. No DLT and SAE were reported. No immune-related grade 2 (G2) or higher adverse reactions were reported. Treatment-related adverse events (TRAEs) occurred in 83% (5/6) of pts (G3 in 17% [1/6], no G4, none leading to treatment interruption or discontinuation). Most frequent TRAEs (≥2 pts) were hypothyroidism (33%, 2/6) and ALT increased (33%, 2/6). PK profile for Chinse pts is consistent with that in Caucasian pts. Of 5 evaluable heavily pretreated pts, ORR was 100% (5/5, 3 CR and 2 PR). All 3 pts achieved CR at the first tumor assessment (i.e., week 8) and remained in CR at the last assessment (i.e., week 24) prior to data cutoff. The other 2 pts achieved PR at week 8 and the responses are still ongoing. Conclusions: The reported safety profile and encouraging early antitumor activity of AK105 supports continued clinical development, which include: pivotal studies in relapsed/refractory cHL and metastatic nasopharyngeal carcinoma, phase 2/3 combination studies with chemotherapy in NSCLC and combination study with anlotinib, a multi-targeting tyrosine kinase inhibitor in hepatocellular carcinoma. Clinical trial information: NCT03722147.