European Society For Medical Oncology Research Articles

Prognostic value of examined lymph node count in patients with lymph node negative pancreatic head carcinoma: A single-center experience

Background/Aim: One of the important prognostic factors for pancreatic cancer is the count of examined lymph nodes (ELN). The ratio of metastatic to ELNs reflects survival and is required for accurate staging. The survival effect of the count of ELNs in patients with an absence of metastatic lymph nodes is unclear. However, the single-center survival outcomes related to higher ELN count based on only lymph node negative-patients are limited to a few studies with controversial results. We aimed to present the single-center experience in survival outcomes based on ELN count in patients with lymph node-negative pancreatic head cancer after pancreaticoduodenectomy. Methods: The data of 129 patients who underwent pancreaticoduodenectomy for pancreatic cancer from October 2011-December 2021 were analyzed. Among them, those who had metastatic lymph nodes, those who died from non-PC causes, died in the first 90 days postoperatively, or had missing follow-up data were excluded. Finally, 37 patients with negative lymph nodes who satisfied our criteria were included. The cut-off value for the examined lymph node count was 15, according to the minimum LN count recommended by the International Study Group of Pancreatic Surgery and the European Society for Medical Oncology for accurate staging. Thus, node-negative patients were divided into ELN

The Carbon Costs of In-Person Versus Virtual Medical Conferences for the Pharmaceutical Industry: Lessons from the Coronavirus Pandemic.

BackgroundMany in-person congresses have shifted to a virtual format owing to coronavirus disease 2019 (COVID-19). We assessed carbon emissions savings associated with virtual attendance at international medical congresses for a mid-sized pharmaceutical company, to identify which aspects are driving the carbon cost.MethodsWe assessed carbon emissions that were the responsibility of company attendees (including their guests) for the most attended congresses by employees (American Society of Clinical Oncology [ASCO], European Neuroendocrine Tumor Society [ENETS], European Society for Medical Oncology [ESMO], World Congress for NeuroRehabilitation [WCNR]). For in-person estimates, we considered travel, accommodation and congress attendance; for online estimates, we considered office and internet-related energy use. Emissions were defined using recognised data sources.ResultsFor 1723 anticipated in-person attendees, calculated total carbon emissions were 3,262,574 kgCO2e (mean per in-person company attendee, 1894 kgCO2e: ASCO, 4172; ESMO, 1479; WCNR, 1153; ENETS, 1009). For context, the average UK resident’s annual carbon footprint is 5600 kgCO2e. Travel accounted for 91–96% of total emissions, mainly through long distance and business-class air travel. Calculated total carbon emissions associated with 1839 virtual attendees were 19,095 kgCO2e (mean per virtual company attendee, 10.4 kgCO2e; equivalent to approximately 0.3–1.1% of in-person attendance emissions across all four congresses assessed).ConclusionCarbon emissions associated with virtual attendance were two orders of magnitude lower than for in-person attendance, and therefore the benefits of in-person attendance at medical congresses must be balanced against the carbon cost. Due diligence around who should attend and how they should travel to face-to-face meetings, and consideration of hybrid and domestic satellite options could be part of a balanced solution to reducing carbon emissions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40290-022-00421-3.

Chorioallantoic membrane tumor models highlight the effects of cisplatin compounds in oral carcinoma treatment

SummaryThe European Society for Medical Oncology (ESMO) suggests the use of chemotherapy as neoadjuvant, adjuvant, and concomitant to surgery and radiotherapy for the treatment of oral carcinoma by depending on the cancer stage. The usual drug of choice belongs to the platinum compounds. In this context, the evaluation of the cancer behavior associated with the administration of standard or emerging cisplatin compounds supports the establishment of optimal cancer management. Here, we have assessed and compared the performance of cisplatin alone and contained in biodegradable nanocapsules on standardized chorioallantoic membrane (CAM) tumor models. The vascularized environment and optimized grafting procedure allowed the establishment of solid tumors. The treatments showed antitumor and anti-angiogenic activities together with deregulation of pivotal genes responsible of treatment resistance and tumor aggressiveness. This study further supports the significance of CAM tumor models in oncological research for the comprehension of the molecular mechanisms involved in tumor treatment response.

Putative germline findings in tumor-only and liquid biopsy sequencing in veterans with aggressive prostate cancer.

179 Background: Tumor-only and/or liquid-biopsy based Next Generation Sequencing (NGS)-based tests, which are routinely performed in metastatic prostate cancer patients, may identify putative germline mutations. The European Society of Medical Oncology (ESMO) made recommendations on findings which should be referred for germline genetic testing; however, it is unknown the burden of genetic testing referrals that may result from implementation of these recommendations. We therefore determined the frequency of putative germline findings in Veterans with metastatic prostate cancer who have undergone NGS-based sequencing of tumor and/or cell-free DNA (cfDNA) on the Foundation Medicine (FMI) platform. Methods: This is a retrospective analysis of Veterans with FMI NGS testing results reported from January 2019-February 2021 who had prostate cancer as the submitted diagnosis and metastatic diagnosis according to a VINCI natural language processing tool. Raw variant data were extracted from FMI reports and harmonized for variant annotation. Variants were annotated using ANNOVAR. Putative germline mutations were defined as 1) likely pathogenic or pathogenic (LP/P) by Clinvar annotation and VAF> 30%. Mutation rates are reported in genes recommended by ESMO to trigger referral for germline testing in all tumor types and all ages of diagnosis and proposed prostate cancer susceptibility genes ( ATM, BARD1, CHEK2). Results: 1,597 Veterans with metastatic prostate cancer underwent FMI NGS testing (63% White, 33% African American, 4% other). Median age was 66 years, with 78.6% of cases from men >60 years. Of 1,597 prostate cancer patients who underwent blood or tumor testing, n=85 (5.3%) had an LP/P mutation in an ESMO-guideline gene. When mutations in ATM, BARD1 and CHEK2 were added, n=133 (8.3%) of patients had an LP/P mutation. The most commonly identified putative germline findings were in BRCA2 (n=49 patients, 3.1%). 18 patients (1.1%) had mutations in other prostate cancer risk genes on the ESMO list ( BRCA1, MLH1, MSH2, MSH6, PMS2). 18 (1.1%) of patients had putative incidental germline findings, which included mutations in PALB2, BRIP1, RAD51C, RAD51D, SDHC. No putative incidental germline mutations were identified in RET, SDHA, SDHB, SDHD, TSC2, VHL. Comparing self-identified White versus self-identified Black patients, putative germline mutation rates were nearly the same in all ESMO-referral genes combined (8.2% vs 8.5%), BRCA2 (2.9% vs 3.0%), and ATM (2.4% vs 2.1%). Conclusions: While guidelines recommend that all veterans with metastatic prostate cancer undergo germline genetic testing, significant patient and system-level barriers continue to limit access to germline genetic testing for many Veterans. Tumor-only NGS testing, with a low rate of putative incidental findings, can help to prioritize which Veterans should be referred for germline genetic testing.

Criteria used to determine platinum eligibility and first-line (1L) treatment (tx) patterns among platinum-eligible (PE) and -ineligible (PI) patients (pts) with metastatic urothelial cancer (mUC) in France, Germany, Spain, Italy, and the United Kingdom (Eu5).

457 Background: European Society for Medical Oncology (ESMO) guidelines recommend tx for mUC based on cisplatin and platinum eligibility. To date, most real-world analyses have not included physician-confirmed eligibility status. This study collected mUC patient data in Eu5 and summarized the criteria used in the real-world setting to determine PE and 1L tx prescribed based on PE. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world point-in-time study conducted from November 2020 to April 2021. Oncologists and urologists were enrolled in the study and recruited the next 8 eligible pts who came for a consultation. Demographic, clinical characteristics, platinum eligibility, and tx patterns were collected. Results: Physicians provided data on 1,868 mUC pts who were receiving or had completed 1L tx and had a known PE status as determined by a physician prior to 1L tx. Renal function contributed to physicians’ platinum eligibility decisions for 72% of pts; ECOG score and age were used in 59% and 38% of pts, respectively. The mean (SD) age was 69.1 (7.88) years and 73% were men. At initial mUC diagnosis (dx), 25% were PD-L1–positive, 17% were PD-L1–negative, and 58% had either unknown PD-L1 status or were not tested. 87% of pts were PE (55% were eligible for cisplatin and carboplatin; 31% were cisplatin ineligible), and 13% were PI. PE pts who were eligible for cisplatin and carboplatin were younger than cisplatin ineligible and PI pts (66.6, 71.9 and 73.1 years, respectively). The percentage of pts with ECOG 0 or 1 at dx was 92%, 79%, and 67% for cisplatin and carboplatin eligible, cisplatin ineligible, and PI pts respectively. Conclusions: Only a small proportion of pts were classified as PI. The majority of PE pts received guideline-recommended tx with platinum-based regimens in the 1L. Overall, there was limited use of immune checkpoint inhibitor tx in the 1L, with use observed primarily among PI pts. Some guideline deviations were observed, including pts deemed PI who still received platinum-based chemotherapy. Recently, ESMO guidelines were updated to include avelumab for 1L maintenance tx in PE pts. Future studies should evaluate concordance with updated guideline recommendations in PE pts and rationale for guideline deviations.[Table: see text]

Abstract OT2-14-01: CAPItello-292: A phase Ib/III study of capivasertib, palbociclib and fulvestrant, versus placebo, palbociclib and fulvestrant, for endocrine therapy-resistant HR+/HER2− advanced breast cancer

Abstract Background: More than two-thirds of advanced breast cancer (ABC) is hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-). Endocrine therapy (ET) is the core treatment for patients with HR+/HER2- ABC, most commonly an aromatase inhibitor (AI), tamoxifen, or the selective estrogen receptor degrader (SERD), fulvestrant. ET is increasingly also combined with a cyclin-dependent kinase (CDK) 4/6 inhibitor, and this has become the first-line standard of care for HR+/HER2- ABC in many countries. However, despite the fact that combination therapy prolongs life compared with ET alone, most patients eventually develop therapy resistance and HR+/HER2- ABC is considered incurable. Overcoming therapy resistance is a major challenge, partially because it is associated with several different mechanisms. The phosphoinositide 3-kinase/protein kinase/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway regulates cell growth, proliferation and survival. Increased PI3K/AKT/PTEN pathway activity has been observed as one of the key mechanisms driving resistance to the combination therapy of ET and CDK4/6 inhibitors. Capivasertib is a potent selective inhibitor of all three AKT isoforms that suppresses PI3K/AKT/PTEN pathway activity. Capivasertib has demonstrated synergistic anticancer activity with standard ET agents in in vitro and in vivo experimental models. Moreover, the Phase II FAKTION trial found that patients with AI-resistant HR+/HER2- ABC had longer progression-free survival (PFS) when capivasertib was added to fulvestrant therapy, compared with fulvestrant alone. CAPItello-292 is a Phase Ib/III trial examining the safety, tolerability and clinical benefit of adding AKT inhibition (with capivasertib) to combined CDK4/6 inhibition (with palbociclib) and ET (with fulvestrant) for patients with ET-resistant HR+/HER2- ABC. Trial design: CAPItello-292 (NCT04862663) is enrolling patients with HR+/HER2- locally advanced or metastatic breast cancer whose disease progressed or recurred while receiving ET or within 12 months of completing an ET (neo)adjuvant regimen. The Phase Ib trial will identify the recommended Phase III dose (RP3D) for combined capivasertib, palbociclib and fulvestrant therapy. Up to 72 patients will be enrolled for the Phase Ib part. The initial regimen will be capivasertib (320 mg twice daily; 4 days on, 3 days off through each 28-day cycle), palbociclib (125 mg once daily for 21 days of each 28-day cycle) and fulvestrant (500 mg once every 28 days, plus a loading dose on day 15 of the first cycle). In the Phase III part, approximately 628 patients will be randomized 1:1 to receive either the RP3D of the triplet or placebo plus palbociclib and fulvestrant until disease progression, unacceptable toxicity or withdrawal of consent. The Phase III primary endpoint is PFS. Secondary endpoints include safety, tolerability and overall survival, as well as PFS of patients whose tumors have PIK3CA/AKT1/PTEN alterations. The first site for the study was activated in mid-May 2021. As of July 2021, two patients have been dosed in the first cohort. Funding and acknowledgements: CAPItello-292 is funded and overseen by AstraZeneca. AstraZeneca funded medical writing support provided by Rose Goodchild, PhD, of Oxford PharmaGenesis, Oxford, UK. This abstract was previously presented at the 2021 European Society for Medical Oncology (ESMO) Annual Meeting, 3019TiP, Erika Hamilton et al. - Reused with permission. Citation Format: Hope S Rugo, Gaia Schiavon, Lynda M Grinsted, Elza C De Bruin, Maria Teresa Catanese, Erika Hamilton. CAPItello-292: A phase Ib/III study of capivasertib, palbociclib and fulvestrant, versus placebo, palbociclib and fulvestrant, for endocrine therapy-resistant HR+/HER2− advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-14-01.

ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.

Development of a management guide wheel for cervical cancer

We designed and developed a management guide wheel for cervical cancer to facilitate a standard approach and improve the quality of care in managing patients diagnosed with different stages of cervical cancer. Each step of the wheel considers the patient’s current medical condition, FIGO stage, and the possible treatment modalities for cervical cancer in her case. We reviewed existing international guidelines on the management of cervical cancer and compared their respective recommendations. This guide wheel is based on recommendations by the following organizations: the National Comprehensive Cancer Network (NCCN), the Society of Gynecologic Oncology (SGO), the European Society of Gynaecological Oncology (ESGO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), the British Gynaecological Cancer Society (BGCS) and the International Federation of Gynecology and Obstetrics (FIGO).

Prioritising systemic cancer therapies applying ESMO’s tools and other resources to assist in improving cancer care globally: the Kazakh experience

BackgroundIn Kazakhstan, cancer is the second leading cause of death with a major public health and economic burden. In the last decade, cancer care and cancer medicine costs have significantly increased. To improve the efficiency and efficacy of cancer care expenditure and planning, the Kazakhstan Ministry of Health requested assistance from the World Health Organization (WHO) and the European Society for Medical Oncology (ESMO) to review its systemic cancer treatment protocols and essential medicines list and identify high-impact, effective regimens.Materials and methodsESMO developed a four-phase approach to review Kazakhstan cancer treatment protocols: (i) perform a systematic analysis of the country’s cancer medicines and treatment protocols; (ii) cross-reference the country’s cancer protocols with the WHO Model List of Essential Medicines, the ESMO-Magnitude of Clinical Benefit Scale and the European Medicines Agency’s medicine availability and indications database; (iii) extract treatment recommendations from the ESMO Clinical Practice Guidelines; (iv) expert review for all cancer medicines not on the WHO Model List of Essential Medicines and the country treatment protocols.ResultsThis ESMO four-phase approach led to the update of the Kazakhstan national essential cancer medicines list and the list of cancer treatment protocols. This review has led to the withdrawal of several low-value or non-evidence-based medicines and a budget increase for cancer care to include all essential and highly effective medicines and treatment options.ConclusionWhen applied effectively, this four-phase approach can improve access to medicines, efficiency of expenditure and sustainability of cancer systems. The WHO–ESMO collaboration illustrated how, by sharing best practices, tools and resources, we can address access to cancer medicines and positively impact patient care.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus

BackgroundThe COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group.MethodsThis consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance.Results and conclusionThe expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Immunotherapy of head and neck cancer : Highlights of the ASCO and ESMO annual meetings 2021

This year's American Society of Clinical Oncology (ASCO) meeting included interesting data on first-line therapy of nasopharyngeal carcinomas with PD‑1 inhibitors and on checkpoint inhibition in various clinical constellations. At the European Society of Medical Oncology (ESMO) meeting, the results of the CheckMate-651study were presented. All abstracts and presentations from the ASCO and ESMO meetings 2021 on immunotherapy in head and neck cancer (HNSCC) were evaluated for their relevance. The most interesting studies are elaborated upon herein. Studies on locally advanced HNSCC showed an improved response after neoadjuvant pembrolizumab administration.Asecond cycle did not improve the response rate, but the proportion of patients with a good response was almost doubled. The CheckRad CD8study showed an improvement in progression-free survival by induction chemoimmunotherapy with tremelimumab and durvalumab followed by stratification according to the CD8 immune cell infiltrate. Two studies were presented on first-line treatment of recurrent/metastatic nasopharyngeal carcinomas. Chemoimmunotherapy showed ahigher response rate and prolonged progression-free survival with asimilar adverse event profile. In recurrent/metastatic HNSCC, the CheckMate 651study showed an increased duration of response with nivolumab and ipilimumab and higher response rates than pembrolizumab alone. The primary endpoints for overall survival were not achieved. PD‑1 inhibition has great potential to change the therapeutic landscape for nasopharyngeal carcinomas in the future. In HNSCC, CD8 tumor infiltrate presents apromising predictive marker for selecting patients who can benefit from radioimmunotherapy. The combination of nivolumab and ipilimumab did not improve overall survival in palliative first-line therapy; thus, no change in the current standard is expected.

Targeted therapy for advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer.

Targeted therapy for advanced anaplastic lymphoma kinase (<I>ALK</I>)-rearranged non-small cell lung cancer.

Impact of Surgical Margins on Overall Survival after Gastrectomy for Gastric Cancer: A Validation of Japanese Gastric Cancer Association Guidelines on a Western Series

PurposeNo consensus exists on the resection extent needed to ensure oncological safety in gastrectomy for gastric adenocarcinoma (GAC). This study aims to assess the impact of margin adequacy according to Japanese Gastric Cancer Association (JGCA) guidelines on overall survival (OS).Patients and MethodsPatients who underwent surgery for stage I–III GAC at our institution between 2010 and 2017 were included. Margin adequacy according to JGCA, National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) guidelines was assessed, and their predictive value on OS was evaluated with Harrell’s C-index. Patients were analyzed according to their margins’ adherence to JGCA guidelines, and a propensity score matching (PSM) was run. Indication to either total gastrectomy (TG) or distal gastrectomy (DG) according to each guideline was also assessed.ResultsA total of 279 patients were included, of whom 220 (79%) underwent DG. Adequate margins according to JGCA were obtained in 209 patients (75%). On multivariate analysis, JGCA margin adequacy was independently associated with OS, together with American Society of Anesthesiologist class, neoadjuvant chemotherapy, lymphadenectomy extent, R0 resection, and postoperative N stage. After PSM, patients with JGCA adequate margins showed better OS, recurrence-free survival (RFS), and local RFS than patients with JGCA inadequate margins. For 220 DG, JGCA guidelines would have recommended TG in 25 patients (11%), NCCN in 30 (14%), and ESMO in 90 (41%) (p < 0.001).ConclusionAdequacy of surgical resection margins to JGCA guidelines leads to improved survival outcomes and allows for a more organ-preserving approach than Western guidelines.

Initiation of bone-targeted agents in patients with bone metastases and breast or castrate-resistant prostate cancer actively treated in routine clinical practice in Europe.

Guidelines recommend starting bone-targeted agents (BTA), such as zoledronic acid and denosumab, as soon as bone metastases (BMs) are definitively diagnosed in all patients with breast cancer (BC) or castration-resistant prostate cancer (CRPC) whether they are symptomatic or not. Data were analyzed from 1364 patients with BC and 1161 patients with CRPC who had BMs and were receiving anti-cancer therapy in hospitals across six European countries (Belgium, France, Germany, Italy, Spain and the UK). The 731 physicians (medical oncologists or urologists) provided insights in the decision-making factors driving their management of bone health for these patients, and the patient medical records indicated how these decisions were reflected in routine clinical practice. Within three months of a BM diagnosis, 74% of BC and 51% of CRPC patients had initiated treatment with a BTA. Around 12% of BC and 23% of CRPC patients did not receive a BTA following BM diagnosis. Irrespective of the tumour type (BC or CRPC), most physicians prescribed either denosumab or zoledronic acid as first BTA therapy. Physicians reported bone pain as a major decision-making factor to initiate a BTA. The presence of bone complications at BM diagnosis and bone pain at BM diagnosis were found to be significant predictive factors for a BTA initiation, irrespective of tumour type. Despite European Society for Medical Oncology (ESMO) guidance on bone protection irrespective of symptomatic disease, not all patients with BMs received a BTA following a BM diagnosis. This suggests that clinical judgements and patients' communication of their pain to their physicians contributed to the decision to prescribe bone protection therapy in cancer patients.

Monitoring for Anthracycline/Trastuzumab Related Cardiomyopathy in Breast Cancer Patients – A Research Audit Into Clinical Practice

In treatment of breast cancer, anthracyclines, and monoclonal antibody, trastuzumab is commonly implicated in the development of cardiomyopathy. Current European Society for Medical Oncology (ESMO) guidelines [1] recommends baseline evaluation of LVEF (left ventricular ejection fraction) and diastolic function for patients undergoing these anti-cancer and routine surveillance cardiac imaging every 3 months with trastuzumab.

European Society of Medical Oncology (ESMO) - 2021 Annual Congress. Virtual - September 16-21, 2021

European Society of Medical Oncology (ESMO) - 2021 Annual Congress. Virtual - September 16-21, 2021

The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations: acquired resistance mechanisms and strategies to overcome them.

As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for the first-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab and erlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due to several different acquired resistance mechanisms, mainly represented by T790M substitutions and MET amplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment, MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a role for MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatment algorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also represent another useful addition.

Encorafenib plus cetuximab for the treatment of BRAF-V600E-mutated metastatic colorectal cancer.

B-type RAF (BRAF)-V600E mutations in metastatic colorectal cancer (mCRC) have been described in up to 12% of the patients. This mutation confers a bad prognostic and poor response with standard chemotherapy. Unlike the scenario for BRAF mutant melanoma, successful BRAF blockade in mCRC has emerged as a complex path, primarily due to the complex underlying biology of mCRC. The BEACON trial has reshaped the therapeutic landscape of BRAF mCRC demonstrating the benefit of the BRAF inhibitor encorafenib in combination with the anti-epidermal growth factor receptor cetuximab. This paper aims to review the main features of BRAF mCRC as well as to review the development of targeted therapy and biomarkers in this specific population. Finally, a deep insight into the underlying biology and molecular classification of BRAF-V600E mCRC has also been performed. The words ‘BRAF-V600E mutation’, ‘colorectal cancer’, ‘BRAF inhibitors’, ‘consensus molecular subtypes’, ‘encorafenib’, and ‘cetuximab’ were used to identify the clinical trials from phase I to phase III related to the development of BRAF inhibitors in this population. A deep search among international meetings (American Society of Clinical Oncology and European Society of Medical Oncology) has been performed to incorporate the last trials presented. BRAF-V600E mCRC is a challenging disease, mostly because of its molecular biology. The BEACON trial has been the most important therapeutic change in the last decade. Nevertheless, new information regarding biomarkers or novel combinations including BRAF inhibitors plus immune checkpoint inhibitors are also promising.

First-line treatments for advanced hepatocellular carcinoma: a network meta-analysis and cost-effectiveness analysis in China and the United States

Various therapeutic strategies are available for the first-line treatment of patients with advanced hepatocellular carcinoma (aHCC). But which approach is the most cost-effective remains uncertain. This study aims to evaluate the cost-effectiveness of first-line strategies in aHCC patients from the perspective of Chinese and US payers. A network meta-analysis (NMA) and cost-effectiveness study. A NMA was conducted to collect all first-line strategies with aHCC from 1 October 1 2018 until 1 January 2022. The relevant randomized controlled trial literature in PubMed, Embase, and Cochrane Library for the last 3 years were searched. The abstracts of meetings of the American Society of Clinical Oncology, European Society of Medical Oncology, and American Association for Cancer Research were also reviewed. A Markov model that included three states was developed. One-way sensitivity and probabilistic sensitivity analysis were performed to investigate the uncertainty of the economic evaluation. Scenario analysis was conducted to explore the economic benefits of treatment strategies in low-income populations. Base-case analysis in China included 1712 patients showed that atezolizumab combined with bevacizumab, sintilimab combined with bevacizumab, lenvatinib (LEVA), and sorafenib (SORA) added 0.46, 1.25, 0.77, and -1.08 quality-adjusted life-years (QALYs), respectively, compared with donafenib, resulting in an incremental cost-effective ratio of $85607.88, $12109.27, and $1651.47 per QALY at a willingness-to-pay (WTP) of $11101.70/QALY. In the United States, only the incremental cost-effectiveness ratios (ICERs) of SORA was higher that were lower than the WTP threshold ($69375/QALY), and LEVA was the most cost-effective strategy with the ICERs were 25022.13/QALY. The NMA and cost-effectiveness analysis revealed that LEVA is the favorite choice in the first-line treatment of Chinese aHCC patients and US payers' perspective when the WTP was $11101.70/QALY in China and $69375.0/QALY in the United States. This study has been registered on the PROSPERO database with the registration number CRD42021286575.

Development, testing, and implementation of a new procedure to assess the clinical added benefit of pharmaceuticals.

The reimbursement process for innovative health technologies in Hungary lacks any formalized assessment of clinical added benefit (CAB). The aim of this research is to present the development, retrospective testing, and implementation of a local assessment framework for determining the CAB of cancer treatments at the Department of Health Technology Assessment of the National Institute of Pharmacy and Nutrition in Hungary. The assessment framework was drafted after screening existing methods and a retrospective comparison of local reimbursement dossiers to that of German and French methods. The Magnitude of Clinical Benefit Scale of the European Society for Medical Oncology was chosen to rate the extent of CAB in oncology, as part of a conclusion complemented by the assessment of endpoint relevance and the quality of evidence. Several rounds of retrospective assessments have been conducted involving all clinical assessors, iterated with semistructured discussions to consolidate divergence between assessors. External stakeholders were consulted to provide feedback on the framework. Retrospective assessments resulted in average more than 75 percent concordance between assessors on each element of the conclusion. Input from ten stakeholders was also incorporated; stakeholders were generally supportive, and they mostly commented on the concept, the elements of the framework, and its implementation. The procedure is suitable for routine use in the decision-making process to describe the CAB of antineoplastic technologies in Hungary. Further extension of the framework is required to cover more disease areas for structured and comparable conclusions on CAB of innovative health technologies.