Background and Aims
Atezolizumab plus bevacizumab (AtezoBev) is the standard of care for first‐line treatment of unresectable HCC. No evidence exists as to its use in routine clinical practice in ...patients with impaired liver function.
Approach and Results
In 216 patients with HCC who were consecutively treated with AtezoBev across 11 tertiary centers, we retrospectively evaluated treatment‐related adverse events (trAEs) graded (G) according to Common Terminology Criteria for Adverse Events v5.0, including in the analysis all patients treated according to label (n = 202, 94%). We also assessed overall survival (OS), progression‐free survival (PFS), overall response (ORR), and disease control rates (DCR) defined by Response Evaluation Criteria in Solid Tumors v1.1. Disease was mostly secondary to viral hepatitis, namely hepatitis C (n = 72; 36%) and hepatitis B infection (n = 35, 17%). Liver function was graded as Child‐Pugh (CP)‐A in 154 patients (76%) and CP‐B in 48 (24%). Any grade trAEs were reported by 143 patients (71%), of which 53 (26%) were G3 and 3 (2%) G4. Compared with CP‐A, patients with CP‐B showed comparable rates of trAEs. Presence and grade of varices at pretreatment esophagogastroduodenoscopy did not correlate with bleeding events. After a median follow‐up of 9.0 months (95% CI, 7.8–10.1), median OS was 14.9 months (95% CI, 13.6–16.3), whereas median PFS was 6.8 months (95% CI, 5.2–8.5). ORR and DCR were respectively 25% and 73%, with no difference across CP classes.
Conclusions
This study confirms reproducible safety and efficacy of AtezoBev in routine practice. Patients with CP‐B reported similar tolerability compared with CP‐A, warranting prospective evaluation of AtezoBev in this treatment‐deprived population.
In this retrospective study on a real‐life cohort of 216 patients treated with Atezolizumab plus Bevacizumab, the combination did not show any unexpected safety signals. Treatment‐related adverse events were comparable across Child‐Pugh (CP) classes. CP‐B patients achieved similar response rates to CP‐A patients, despite inferior survival outcomes.
IMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC).
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.
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.
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.
•Atezolizumab plus bevacizumab (A + B) is the standard of care for patients with unresectable hepatocellular carcinoma.•We report data from a large cohort of patients treated with A + B in real-life.•Effectiveness and safety of the combination is reproducible in daily practice.•Liver function and macro-vascular invasion is with overall survival.•Radiological response predicts better outcomes.
Prognostic and predictive factors in pancreatic cancer Dell'Aquila, Emanuela; Fulgenzi, Claudia Angela Maria; Minelli, Alessandro ...
Oncotarget,
2020-Mar-10, 2020-03-10, 20200310, Letnik:
11, Številka:
10
Journal Article
Odprti dostop
Pancreatic cancer is one of the leading causes of cancer death worldwide. Its high mortality rate has remained unchanged for years. Radiotherapy and surgery are considered standard treatments in ...early and locally advanced stages. Chemotherapy is the only option for metastatic patients. Two treatment regimens, i. e. the association of 5-fluorouracil- irinotecan-oxaliplatin (FOLFIRINOX) and the association of nab-paclitaxel with gemcitabine, have been shown to improve outcomes for metastatic pancreatic adenocarcinoma patients. However, there are not standardized predictive biomarkers able to identify patients who benefit most from treatments. CA19-9 is the most studied prognostic biomarker, its predictive role remains unclear. Other clinical, histological and molecular biomarkers are emerging in prognostic and predictive settings. The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and fourth-leading cause of cancer death. While drug discovery to improve disease survival was historically poor, there is now ...evidence of significant potential for immune checkpoint inhibitors (ICPIs) in treatment of the disease, and indeed such drug approvals are beginning to emerge.
HCC typically arises in the context of cirrhosis and chronic liver disease (CLD), and HCC exhibits significant biological heterogeneity, in part reflecting the broad range of etiologies of CLD. Different classes and combinations of ICPI-based therapy exist, but not all patients will respond and predictive biomarkers are not yet available to guide clinician decision-making, unlike some other cancer types. In this review, we discuss the emerging biomarkers for ICPI sensitivity in HCC, including tumor genomic features, perturbation of the gut microbiome, and systemic inflammatory markers.
Additional profiling studies are required to appreciate existing trends with clinical outcome and to further drive clinical studies in disease stratification by response. This will only be possible within collaborative and international efforts, especially regarding biopsy collection. A close collaboration between basic scientists and clinicians will be the key to shape the next future of HCC biomarker research.
Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic ...treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs).
After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference.
Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab + IBI350, camrelizumab + rivoceranib, and atezolizumab + bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43–0.75), 0.62 (95% CI 0.49–0.79), and 0.66 (95% CI 0.52–0.84), respectively. Considering PFS, camrelizumab + rivoceranib and pembrolizumab + lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41–0.65) and 0.52 (95% CI 0.35–0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs.
The combinations of ICI + anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates.
In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results.
PROSPERO CRD42022366330.
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•The treatment paradigm for unresectable HCC has changed in the last few years.•The combination of atezolizumab + bevacizumab has become the new standard of care.•Durvalumab + tremelimumab has been shown to confer a survival benefit over sorafenib.•Cabozantinib + atezolizumab has been shown to confer a PFS but not OS benefit over sorafenib.•Lenvatinib + pembrolizumab does not appear to prolong PFS and OS over lenvatinib.
According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients with very early (BCLC-0) and early (BCLC-A) disease can undergo a potentially curative approach, such as surgical ...resection, local ablative therapies and orthotopic liver transplantation (OLT), which is the only curative approach for both HCC and liver cirrhosis. 7 Also, some initial real-life experiences seem to confirm the feasibility and safety of treating CP-B patients with lenvatinib, despite a poor OS compared to CP-A patients. 8 Focusing on second-line options, cabozantinib achieved a significant improvement in OS and progression-free survival (PFS) also in those patients whose liver function deteriorated to CP-B by week 8 of treatment within the CELESTIAL trial. 9 Also, these patients had a similar rate of dose reductions and toxicity-related treatment discontinuations compared to the rest of the population. According to a large retrospective study, CP was confirmed to be a negative prognostic factor; in fact, CP-B patients treated with nivolumab achieved lower OS (7.3 months vs 16.3 months, HR = 1.95, 95% CI 1.35-2.81, P < .001) compared to CP-A patients, but PFS, ORR and TRAEs rate did not appear to be influenced by CP. 14 Among factors defining CP-B class, diuretic-refractory ascites have been reported to carry worse prognostic significance compared to other parameters in CP-B patients receiving nivolumab or pembrolizumab 15; furthermore, albumin–bilirubin grade has been described to better predict survival compared to CP in patients with moderate to severe liver impairment receiving ICI monotherapy. 16 Data about the safety and efficacy of ICI combination therapies in CP-B are currently unavailable.
Systemic inflammation is a key risk factor for hepatocellular carcinoma (HCC) progression and poor outcomes. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and ...platelet-to-lymphocyte ratio (PLR) may have prognostic value in HCC treated with standard of care atezolizumab plus bevacizumab (Atezo-Bev). We conducted a multicenter, international retrospective cohort study of patients with unresectable HCC treated with Atezo-Bev to assess the association of NLR and PLR with overall survival (OS), progression-free survival (PFS), and objective response rates. Patients with NLR ≥ 5 had a significantly shorter OS (9.38 vs. 16.79 months, p < 0.001) and PFS (4.90 vs. 7.58 months, p = 0.03) compared to patients with NLR < 5. NLR ≥ 5 was an independent prognosticator of worse OS (HR 2.01, 95% CI 1.22−3.56, p = 0.007) but not PFS. PLR ≥ 300 was also significantly associated with decreased OS (9.38 vs. 15.72 months, p = 0.007) and PFS (3.45 vs. 7.11 months, p = 0.04) compared to PLR < 300, but it was not an independent prognosticator of OS or PFS. NLR and PLR were not associated with objective response or disease control rates. NLR ≥ 5 independently prognosticated worse survival outcomes and is worthy of further study and validation.
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