ML-12 Clinical impact and management of skin-related disorders during treatment of relapsed PCNSL by tirabrutinib

Abstract BACKGROUNDS: Tirabrutinib is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, approved by the Japanese Pharmaceutical and Medical Devices Agency (PMDA) for relapsed and refractory PCNSL in March 2020. Skin-related disorder (SRD)s are the most prevalent adverse events in tirabrutinib, which accounted for 54.5% in a phase I/II trial. While the use of tirabrutinib is increasingly considered in clinical practice, the prevalence and clinical impact of tirabrutinib-related SRDs in real-world practice remains unclear. METHODS: Relapsed PCNSL patients treated with tirabrutinib at the author’s institution were identified, and divided into those with SRDs (SRD group), and without SRDs (non-SRD group). Response rate and progression-free survival (PFS) were retrospectively analyzed and compared between the two groups. RESULTS: Eleven patients were identified (median age: 73 [range: 50–83], median KPS: 70 [range: 40–90]), which included six (54.5%) from the SRD group and five (45.5%) from the non-SRD group. Response rate was 100% in the SRD group and 60% in the non-SRD group. Median PFS was 2.8 months in the SRD group and 36.3 months in the non-SRD group, which yielded no significant difference (p=0.446). While antihistamine prophylaxis using fexofenadine was performed in seven patients, among them SRDs were observed in three (27.3%). SRDs lead to tirabrutinib interruption (for seven days or more) in two (18.2%), dose reduction in three (27.3%), and discontinuation in two (18.2%) patients. Four patients in whom tirabrutinib was interrupted or discontinued due to SRDs had shorter PFS, compared with the two patients from the SRD group in whom tirabrutinib was continued (median PFS: 2.3 and 29.6 months, respectively) (p=0.049). CONCLUSIONS: SRDs substantially lead to tirabrutinib interruption or discontinuation, which could result in early PD. Since fexofenadine prophylaxis seems ineffective for preventing SRDs, other antihistamines should be considered. Establishment of the optimal management of tirabrutinib-related SRDs is warranted.

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Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1087 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1087-1087

Author(s):

Zhongsheng Tong ◽

Shufen Li ◽

Yehui Shi ◽

Xu Wang ◽

Chen Wang ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Response Rate ◽

Metastatic Breast ◽

Progression Free Survival ◽

Phase Iii ◽

First Line ◽

Free Survival ◽

Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

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Interferon Alpha May Improve the prognosis of Advanced Myeloproliferative Neoplasm Patients with JAK2V617F Mutations

Blood ◽

10.1182/blood.v124.21.5547.5547 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5547-5547

Author(s):

Liu Xiaoli ◽

Li Ding ◽

Na Xu ◽

Bintao Huang ◽

Xuan Zhou ◽

...

Keyword(s):

Survival Rate ◽

Adverse Reactions ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Essential Thrombocytosis ◽

Free Survival ◽

Overall Response ◽

Significant Difference ◽

Hydroxyurea Therapy

Abstract Objective Whetherinterferon alpha (IFN-α) has special therapeutic effect formyeloproliferative neoplasm (MPN) patients with JAK2V617F mutations was not widely confirmed. Our purpose was to evaluate the therapeutic effect of interferon alpha (IFN-α) in MPN patients with JAK2V617F mutations. Methods A total of 99 advanced MPN patients (including 68 polycythemia vera (PV) patients with 34 JAK2V617F mutations and 68 essential thrombocytosis (ET) with JAK2V617F mutations) patients) were enrolled to the study during 2007 to 2013 with informed consent, then they were divided into two groups: the IFN-α group (patients received a standard dose of IFN-α with (30-50)ug/d ) and the Hydroxyurea (HU) group (patients received a a dose of (0.25-0.5)g/d for HU). The progression-free survival rate were analyzed for a median of 32.0 (6.0 to 60.0) months follow-up period. Results The overall response rate between IFN-α and Hydroxyurea therapy groups of essential thrombocytosis (ET) patients with JAK2V617F mutations had no significant difference (88.2% vs 85.0%, P>0.05), but the 5-year progression-free survival rate of two groups showed significant difference (88.2% vs 55.0%, P<0.05). The overall response rate (78.6% vs 82.4% ) and 5-year progression-free survival rate (57.1% vs 58.8%) between IFN-α and Hydroxyurea therapy groups of ET patients without JAK2V617F mutations had no significant difference (P>0.05). The overall response rate between IFN-α and Hydroxyurea therapy groups of polycythemia vera (PV) patients with JAK2V617F mutations had no significant difference (80.0% vs 75%, P>0.05), but the 5-year progression-free survival rate of IFN-α and Hydroxyurea therapy groups showed significant difference (86.7% vs 50.0%, P<0.05). After the treatment of IFN-α and HU for six months, the ratio of Interferon-treated patients need to continue phlebotomy was significantly lower than hydroxyurea therapy group (8.3% vs 58.3%, P<0.05). The thromboembolic events,splenomegaly, bone marrow fibrosis of interferon treatment group were lower than hydroxyurea treatment group showed significant difference (P<0.05). The adverse reactions of IFN-α was moderate, most of the patients in this study could tolerate the therapy. The major side effect of hydroxyurea was hematologic adverse reactions (Grade 1-2) with mainly reduce of white blood cells and thrombocytopenia, which showed difference between IFN-α and hydroxyurea (P<0.05). Conclusions IFN-α may improve the prognosis of ET and PV patients with JAK2V617F mutations. Moreover, patients with PV and JAK2V617F mutations may be benefit for the treatment of IFN-α and could be recommended for an effective choice. Disclosures No relevant conflicts of interest to declare.

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Toxicity and effectiveness of carboplatin in obese or overweight patients

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218790339 ◽

2018 ◽

Vol 25 (6) ◽

pp. 1328-1335 ◽

Cited By ~ 1

Author(s):

Cristina Grueso Cuesta ◽

Jaime E Poquet Jornet ◽

Juan M Gasent Blesa ◽

Antonio Valdivia Perez ◽

Francisco J Carrera Hueso ◽

...

Keyword(s):

Overall Survival ◽

Body Weight ◽

Actual Body ◽

Response Rate ◽

Progression Free Survival ◽

Normal Weight ◽

Actual Body Weight ◽

Free Survival ◽

Significant Difference ◽

Dose Reductions

Objective To evaluate the efficiency and toxicity of carboplatin using actual body weight in obese/overweight patients using the Calvert formula with Cockcroft–Gault for CrCl estimation. Methods We evaluated the association of BMI in regards to efficiency and toxicity in a retrospective cohort study of patients who started treatment with carboplatin between 2012 and 2013. Cohorts included obese/overweight patients and normal-weight patients. Efficiency was measured by overall survival, progression-free survival and response rate. Toxicity was measured by the proportion of dose reductions and delays of chemotherapy cycles. We utilized a bivariate and multivariate analysis. Results Eighty-six patients were included in the study (50% obese/overweight). There was not a statistically significant difference in effectiveness and toxicity between the two groups in BMI. In the multivariate analysis, BMI not was associated with overall survival (hazard ratio: 0.95, 95% CI: 0.54–1.66, p = 0.849), progression-free survival (hazard ratio: 0.91; 95% CI: 0.54–1.54; p = 0.732), cycle delays (odds ratio (OR): 1.47, 95% CI: 0.80–2.69, p = 0.218) or carboplatin dose reductions (OR: 0.87, 95% CI: 0.35–2.15, p = 0.760). Response rate was 53.5% in both groups. Conclusions In our study, obese and overweight cancer patients did not show a statistically significant difference in terms of effectiveness and toxicity compared to normal-weight cancer patients who were treated with carboplatin using their actual body weight with the Calvert formula and Cockcroft–Gault for CrCl estimation. Therefore, it was appropriate to use the actual body weight for our patients.

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Outcomes of Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs)

Cancers ◽

10.3390/cancers12010206 ◽

2020 ◽

Vol 12 (1) ◽

pp. 206 ◽

Cited By ~ 5

Author(s):

Katharine Thomas ◽

Brianne A. Voros ◽

Meghan Meadows-Taylor ◽

Matthew P. Smeltzer ◽

Ryan Griffin ◽

...

Keyword(s):

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Neuroendocrine Neoplasms ◽

Ki 67 ◽

Free Survival ◽

Median Progression Free Survival ◽

Significant Difference ◽

Number Of Cycles ◽

Lower Hazard

Capecitabine and temozolomide (CAPTEM) have shown promising results in the treatment of neuroendocrine neoplasms (NEN). The aim of this study was to evaluate the outcome and role for CAPTEM in malignant neuroendocrine neoplasms. Data were obtained from NEN patients who received at least one cycle of CAPTEM between November 2010 and June 2018. The average number of cycles was 9.5. For analysis, 116 patients were included, of which 105 patients (91%) underwent prior treatment. Median progression free survival (PFS) and overall survival (OS) were 13 and 38 months, respectively. Overall response rate (ORR) was 21%. Disease control rate (DCR) was 73% in all patients. PFS, median OS, ORR, and DCR for pancreatic NENs (pNEN) vs. non-pNEN was 29 vs. 11 months, 35 vs. 38 months, 38% vs. 9%, and 77% vs. 71%, respectively. Patients with pNEN had a 50% lower hazard of disease progression compared to those with non-pNEN (adjusted Hazard Ratio: 0.498, p = 0.0100). A significant difference in PFS was found between Ki-67 < 3%, Ki-67 3–20%, Ki-67 > 20–54%, and Ki-67 ≥ 55% (29 vs. 12 vs. 7 vs. 5 months; p = 0.0287). Adverse events occurred in 74 patients (64%). Our results indicate that CAPTEM is associated with encouraging PFS, OS, and ORR data in patients with NENs.

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Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma

Blood ◽

10.1182/blood-2018-09-874396 ◽

2019 ◽

Vol 133 (18) ◽

pp. 1953-1963 ◽

Cited By ~ 26

Author(s):

Thierry Facon ◽

Jae Hoon Lee ◽

Philippe Moreau ◽

Ruben Niesvizky ◽

Meletios Dimopoulos ◽

...

Keyword(s):

Multiple Myeloma ◽

Response Rate ◽

Residual Disease ◽

Progression Free Survival ◽

Complete Response ◽

Newly Diagnosed ◽

Free Survival ◽

Intention To Treat ◽

Significant Difference ◽

Grade 3

Abstract The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease–negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials.gov as #NCT01818752.

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Efficacy of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer: A real life experience and outcome from a tertiary referral centre.

Journal of Cancer & Allied Specialties ◽

10.37029/jcas.v7i2.409 ◽

2021 ◽

Vol 7 (2) ◽

Author(s):

Samia Yasmeen ◽

Sabah Shaukat ◽

Farah Arshad ◽

Farhana Badar ◽

Syed Ather Saeed Kazmi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Response Rate ◽

Chemotherapy Regimen ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Free Survival ◽

Significant Difference

Introduction: To report response rate, progression-free survival and overall survival in patients with advanced pancreatic cancer treated with different available chemotherapeutic regimens over ten years. Materials and Methods: This is a retrospective observational study. All patients with locally advanced and metastatic pancreatic cancer at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from January 2008 to December 2017 were studied. Data were collected from the hospital information system. The characteristics and outcomes of all the patients were analyzed. Progression-free survival and overall survival were also estimated. Kaplan Meier curves and Log-rank test were applied, and SPSS version 20 was used for data analysis. Results: Eighty-seven (87) subjects with a median age of 56 years (range 21-76) were included. Sixty-two (71%) subjects were male. The most common tumor location was the head of the pancreas in 46(53%) of all the subjects. Sixty-three (72%) subjects had elevated CA-19.9 values. About 47(54%) subjects had locally advanced pancreatic cancer (LAPC), and 40(46%) subjects had metastatic pancreatic cancer (MPC). Chemotherapy regimens used were FOLFIRINOX in 23(26%), gemcitabine-based 66(65%) and capecitabine-based in 8 (9%) of the subjects. One (1%) subject had a complete response (CR), 12(14%) had a partial response (PR), 10 (11%) had stable disease, and 59(68%) of the subjects had progressive disease (PD). The objective response rate (ORR) was 15%, and the disease control rate (DCR) was 26%. In MPC, the ORR was 10%, DCR was 18%, and tumor progression was seen in 72% of the patients, while in LAPC, the ORR was 19.1, DCR 34% and tumor progression was documented in 64% of the patients, respectively. The FOLFIRNOX chemotherapy regimen had better ORR, DCR and lesser number of progressions as compared to Gemcitabine and Capecitabine based chemotherapy regimens. The Median PFS of the whole group was 32-weeks, and the median OS was 54-weeks. The PFS was significantly higher for LAPC (39 weeks) as compared to the MPC group (25 weeks) (p=0.028). There was no statistically significant difference between the OS of these 2 groups (p=0.451). In addition, PFS was significantly higher with FOLFIRINOX chemotherapy as compared to the other chemotherapy regimens. Regarding OS, there was no statistically significant difference among all chemotherapy regimen groups (p=0.267). Conclusion: Based on our results, FOLFIRINOX remained the most effective chemotherapy regimen despite the dose modifications and toxicities in all groups, indicating that modified FOLFIRINOX could be considered as a first-line regimen in south East Asian population.

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Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽

10.3390/cancers13102489 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2489

Author(s):

Sazan Rasul ◽

Tim Wollenweber ◽

Lucia Zisser ◽

Elisabeth Kretschmer-Chott ◽

Bernhard Grubmüller ◽

...

Keyword(s):

Response Rate ◽

Cox Regression ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Free Survival ◽

Castration Resistant ◽

Kaplan Meier ◽

Node Metastases ◽

Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

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Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06175-x ◽

2021 ◽

Author(s):

Pavani Chalasani ◽

Kiah Farr ◽

Vicky Wu ◽

Isaac Jenkins ◽

Alex Liu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Peripheral Neuropathy ◽

Clinical Benefit ◽

Low Dose ◽

Response Rate ◽

Metastatic Breast ◽

Progression Free Survival ◽

Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

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A survival analysis of surgically treated incidental low-grade glioma patients

Scientific Reports ◽

10.1038/s41598-021-88023-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingcheng Zeng ◽

Qi Mei ◽

Hua Li ◽

Changshu Ke ◽

Jiasheng Yu ◽

...

Keyword(s):

Progression Free Survival ◽

Low Grade Glioma ◽

Low Grade ◽

Total Resection ◽

Surgical Timing ◽

Asymptomatic Group ◽

Free Survival ◽

Symptomatic Group ◽

Significant Difference ◽

Asymptomatic Phase

AbstractTo evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase.

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Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

Scientific Reports ◽

10.1038/s41598-021-96089-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Atsushi Hiraoka ◽

Takashi Kumada ◽

Toshifumi Tada ◽

Joji Tani ◽

Kazuya Kariyama ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Liver Disease ◽

Hazard Analysis ◽

Progression Free Survival ◽

Significant Prognostic Factor ◽

Disease Etiology ◽

Alcoholic Fatty Liver ◽

Free Survival ◽

Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

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