310 results found
Fulgenzi CAM, D'Alessio A, Airoldi C, et al., 2022, Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials., Eur J Cancer, Vol: 174, Pages: 57-67
BACKGROUND: Dual programmed cell death-1 and vascular endothelial growth factor pathway inhibition is the novel standard of care for patients with unresectable hepatocellular carcinoma. Direct comparisons between first-line treatments are lacking. METHOD: We conducted a literature search in MEDLINE (https://pubmed.ncbi.nlm.nih.gov), the Cochrane library (https://www.cochranelibrary.com) and Embase (www.embase.com) between January 2007 and February 2022. We included phase III randomised controlled trials that tested immune-checkpoint inhibitors or tyrosine kinase inhibitors, including sorafenib, lenvatinib and donafenib, and evaluated as primary end-point overall survival (OS) or progression-free survival (PFS). Studies testing loco-regional therapies were excluded. The primary end-point was to compare the efficacy of first-line options in terms of OS and PFS. We extracted Hazard ratios (HR) and 95% confidence intervals (95% CI) for OS and PFS and performed a frequentist network meta-analysis with fixed effect multivariable meta-regression models. The research protocol was registered in PROSPERO, an international prospective register of systematic reviews (registration code CRD42022312489). FINDINGS: Literature review yielded 13709 results, after duplicates removal and exclusion of not relevant studies, 70 papers were available for screening. After full-text review, 9 studies were eligible for analysis. Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74
Fulgenzi CAM, Cheon J, D'Alessio A, et al., 2022, Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study., Eur J Cancer, Vol: 175, Pages: 204-213
BACKGROUND: IMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC). METHODS: We generated a prospectively maintained database including patients treated with atezolizumab plus bevacizumab for unresectable HCC across Europe, Asia and USA. Clinico-pathologic characteristics were assessed for their prognostic influence on overall survival (OS) and progression-free survival (PFS) in univariable and multivariate analyses. Overall response rate by RECIST v1.1 and treatment-related adverse events (TRAEs) per CTCAE v.5.0 were reported. RESULTS: Out of 433 patients, 296 Child-Pugh A and ECOG performance status01 patients received atezolizumab plus bevacizumab in first line and were included. Patients were mostly male (82.7%), cirrhotic (75%) with history of viral hepatitis (65.9%). Overall, 68.9% had Barcelona Clinic Liver Cancer C-stage HCC with portal vein tumour thrombosis (PVTT, 35%) and extrahepatic spread (EHS, 51.7%). After a median follow-up of 10.0 months (95% confidence interval (CI): 9.4-10.4), median OS and PFS were 15.7 (95% CI: 14.5-NE) and 6.9 months (95% CI: 6.1-8.3), respectively. In the response-evaluable patients (n = 273), overall response rate was 30.8%. Overall, 221 patients (74.6%) developed TRAEs, with 70 (23.6%) reporting grade 3 or higher TRAEs; 25 (8.4%) patients had bleeding events. OS was independently associated with baseline Albumin-bilirubin (ALBI) grade and PVTT. Shorter PFS was associated with AFP≥ 400 ng/ml, worse ALBI and presence of EHS. CONCLUSION: This global observational study confirms the reproducible safety and efficacy of atezolizumab plus bevacizumab in routine clinical practice. Within Child-Pugh-A criteria, the presence of PVTT and higher ALBI grade identify patients with poorer survival.
Vithayathil M, D'Alessio A, Fulgenzi CAM, et al., 2022, Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma, Publisher: WILEY, Pages: S374-S375, ISSN: 1478-3223
Takada K, Buti S, Bersanelli M, et al., 2022, Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade, EUROPEAN JOURNAL OF CANCER, Vol: 172, Pages: 199-208, ISSN: 0959-8049
Cortellini A, Aguilar-Company J, Salazar R, et al., 2022, Natural immunity to SARS-CoV-2 and breakthrough infections in vaccinated and unvaccinated patients with cancer, BRITISH JOURNAL OF CANCER, ISSN: 0007-0920
D'Alessio A, Pinato DJ, 2022, Dissecting the tumour microenvironment to predict immunotherapy response in hepatocellular cancer., Gastroenterology
Barsch M, Salie H, Schlaak AE, et al., 2022, T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma, JOURNAL OF HEPATOLOGY, Vol: 77, Pages: 397-409, ISSN: 0168-8278
D'Alessio A, Fulgenzi CAM, Pinato DJ, 2022, Untitled Reply, HEPATOLOGY, ISSN: 0270-9139
Johnson PJ, Pinato DJ, Kalyuzhnyy A, et al., 2022, Breaking the Child-Pugh Dogma in Hepatocellular Carcinoma comment, JOURNAL OF CLINICAL ONCOLOGY, Vol: 40, Pages: 2078-+, ISSN: 0732-183X
D'Alessio A, Weinmann A, Galle P, et al., 2022, Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study, JOURNAL OF HEPATOLOGY, Vol: 77, Pages: S376-S376, ISSN: 0168-8278
Cortellini A, Salazar R, Gennari A, et al., 2022, Original Research Persistence of long-term COVID-19 sequelae in patients with cancer: An analysis from the OnCovid registry, EUROPEAN JOURNAL OF CANCER, Vol: 170, Pages: 10-16, ISSN: 0959-8049
Sharma R, Pillai A, Marron TU, et al., 2022, Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC, Hepatology Communications, Vol: 6, Pages: 1776-1785, ISSN: 2471-254X
The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post-ICI survival. We established an international consortium of 11 tertiary-care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post-ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post-ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post-ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.
Munoz-Martinez S, Sapena V, Forner A, et al., 2022, Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study, LIVER INTERNATIONAL, Vol: 42, Pages: 1891-1901, ISSN: 1478-3223
Cortellini A, Ricciuti B, Borghaei H, et al., 2022, Differential prognostic effect of systemic inflammation in patients with non-small cell lung cancer treated with immunotherapy or chemotherapy: A post hoc analysis of the phase 3 OAK trial, CANCER, Vol: 128, Pages: 3067-3079, ISSN: 0008-543X
Marinelli B, Kim E, D'Alessio A, et al., 2022, Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study, JOURNAL FOR IMMUNOTHERAPY OF CANCER, Vol: 10
Fulgenzi CAM, D'Alessio A, Ogunbiyi O, et al., 2022, Novel immunotherapy combinations in clinical trials for hepatocellular carcinoma: will they shape the future treatment landscape?, EXPERT OPINION ON INVESTIGATIONAL DRUGS, Vol: 31, Pages: 681-691, ISSN: 1354-3784
Serra C, Cossiga V, Serenari M, et al., 2022, Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma: a textbook outcome analysis, HPB, Vol: 24, Pages: 664-671, ISSN: 1365-182X
Cortellini A, Gennari A, Pommeret F, et al., 2022, COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 114, Pages: 979-987, ISSN: 0027-8874
Chrysostomou S, Roy R, Prischi F, et al., 2022, Re: Repurposed Floxacins Targeting RSK4 Prevent Chemoresistance and Metastasis in Lung and Bladder Cancer, JOURNAL OF UROLOGY, Vol: 207, Pages: 919-920, ISSN: 0022-5347
Mallardo D, Cortellini A, Capone M, et al., 2022, Concomitant type 2 diabetes mellitus (T2DM) in metastatic melanoma patients could be related to lower level of LAG-3: a transcriptomic analysis of a retrospective cohort, ANNALS OF ONCOLOGY, Vol: 33, Pages: 445-447, ISSN: 0923-7534
Talukder R, Makrakis D, Diamantopoulos LN, et al., 2022, Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin, CLINICAL GENITOURINARY CANCER, Vol: 20, Pages: 165-175, ISSN: 1558-7673
Muhammed A, D'Alessio A, Enica A, et al., 2022, Predictive biomarkers of response to immune checkpoint inhibitors in hepatocellular carcinoma, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 22, Pages: 253-264, ISSN: 1473-7159
Cattrini C, Manfredi M, Barboro P, et al., 2022, Lipidomic profiling in patients with heavily pretreated castration-resistant prostate cancer., Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Cortellini A, Ricciuti B, Vaz VR, et al., 2022, Prognostic effect of body mass index in patients with advanced NSCLC treated with chemo-immunotherapy combinations, Journal for ImmunoTherapy of Cancer, Vol: 10, Pages: 1-10, ISSN: 2051-1426
Introduction: It has been recognised that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICI) in patients with various malignancies including NSCLC. However, it is unclear whether baseline BMI may influence outcomes from first-line chemo-immunotherapy combinations. Methods: In this international multicentre study we evaluated the association between baseline BMI, progression free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemo-immunotherapy combinations. BMI was categorized according to World Health Organization criteria.Results: Among the 853 included patients, 5.3% were underweight, 46.4% were of normal weight, 33.8% were overweight and 14.5% were obese. Overweight and obese patients were more likely aged ≥70 years (p=0.00085), never smokers (p<0.0001), with better baseline ECOG-PS (p=0.0127), lower prevalence of CNS (p=0.0002) and liver metastases (p=0.0395). Univariable analyses showed a significant difference in the median OS across underweight (15.5 months), normal weight (14.6 months), overweight (20.9 months) and obese (16.8 months) patients (log-rank for trend: p = 0.131), whilst no difference was found with respect to the median PFS (log-rank for trend: p = 0.510). Neither OS nor PFS were significantly associated with baseline BMI on multivariable analysis. Conclusions: In contrast to what observed in the context of chemotherapy free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemo-immunotherapy combinations in patients with advanced NSCLC.
Wu L, Ozbek U, van Hyfte G, et al., 2022, Outcomes of beta blockers (BB) in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
D'Alessio A, Weinmann A, Galle PR, et al., 2022, Real-world use of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Scheiner B, Pomej K, Kirstein MM, et al., 2022, Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score, JOURNAL OF HEPATOLOGY, Vol: 76, Pages: 353-363, ISSN: 0168-8278
Cortellini A, Giusti R, Filetti M, et al., 2022, High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status, Journal of Hematology and Oncology, Vol: 15, ISSN: 1756-8722
Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted.
Muhammed A, Fulgenzi CAM, Dharmapuri S, et al., 2022, The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma, CANCERS, Vol: 14
Colmenero J, Tabrizian P, Bhangui P, et al., 2022, De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management-Guidelines From the ILTS-SETH Consensus Conference, TRANSPLANTATION, Vol: 106, Pages: E30-E45, ISSN: 0041-1337
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