European Society For Medical Oncology Research Articles

Role of adjuvant systemic therapy in high-risk renal cell carcinoma

BackgroundVascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF TKIs) and immune checkpoint inhibitors (ICIs) have been shown to be effective and safe in the treatment of metastatic renal cell carcinoma. Thus, the use of these agents is being evaluated in the adjuvant therapeutic setting following surgical resection.ObjectiveThis article provides a review of positive and negative results from clinical trials assessing the adjuvant treatment of renal cell carcinoma.Materials and methodsFor the review, relevant phase III studies as well as recent conference abstracts (American Society of Clinical Oncology [ASCO], European Society of Medical Oncology [ESMO]) and current guidelines (European Association of Urology [EAU]) were summarized, considering clinical relevance, and providing a critical interpretation.Results and conclusionCurrently, adjuvant therapy with the PD‑1 inhibitor pembrolizumab is recommended for 1 year in patients with high-risk renal cell carcinoma (defined by KEYNOTE-564). Other checkpoint inhibitors (atezolizumab, nivolumab+ipilimumab, nivolumab) as well as VEGF TKIs are accompanied by high toxicity and show no advantage in the adjuvant therapy.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies.

Highlighting selected research conducted in older patients presented at the European Society for Medical Oncology (ESMO) 2022 Congress – a Young International Society of Geriatric Oncology (SIOG) perspective

Highlighting selected research conducted in older patients presented at the European Society for Medical Oncology (ESMO) 2022 Congress – a Young International Society of Geriatric Oncology (SIOG) perspective

Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is often painful and can arise during or after the end of oncological treatments. They are mostly induced by platinum salts, taxanes, and immunotherapies. Their incidence is estimated between 19 and 85%. They can require a chemotherapy dose reduction or early termination. The European Society for Medical Oncology (ESMO) recommends high-concentration capsaicin patch (HCCP) in second line for the treatment of painful CIPN. This treatment induces a significative pain relief but only shown by low-powered studies. The objective of this study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Methods: This monocentric observational retrospective real-world-data study of the CERCAN cohort took place in the Western Cancer Institute's Anaesthesiology and Pain Department at Angers, France. Independent pain physicians completed the CGIC (Clinician Global Impression of Change) for each patient who benefited from HCCP applications for painful CIPN starting from 1 January 2014 to 22 December 2021, based on the collected data after every patch application. Results: A total of 57 patients (80.7% women) was treated with HCCP for painful CIPN, and 184 applications were realized, consisting of 296 sessions. CGIC found an important or complete pain relief for 61 applications (33.2%, corresponding to 43.9% patients). We found less efficacy for platinum-salts-induced CIPN compared to others (p = 0.0238). The efficacy was significatively higher for repeated applications when HCCP was used in second line compared to third line (p = 0.018). The efficacy of HCCP was significatively higher starting the third application (p = 0.0334). HCCPs were mainly responsible for local adverse events found in 66.6% patients (65.1% burning or painful sensation, 21.1% erythema). Conclusion: HCCP applications in painful CIPN induce an important pain relief with a global satisfying tolerability.

Discrepancy between recommendations regarding hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer management: a narrative review.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversial in ovarian cancer (OC) management. Doubts are related mainly to HIPEC effectiveness, but also to its safety. European Society of Medical Oncology and European Society of Gynecologic Oncology do not consider HIPEC as a standard of care. Opposite to European recommendations, National Comprehensive Cancer Network found HIPEC as a treatment option in patients undergoing interval debulking surgery in first-line treatment. This may be confusing for oncologists in clinical practice. The aim of this narrative review is to present literature review focusing on efficacy, confounding factors, complications and immunological issue of HIPEC in OC management. PubMed was searched for meta-analyses, randomized trials, observational studies, experimental studies to outline the role of HIPEC in OC management since January 2015 until August 2023. Keywords included "hyperthermic intraperitoneal chemotherapy", "HIPEC", "ovarian cancer", "immune response". References from full-text articles were screened for additional studies. Most meta-analyses found that HIPEC improved survival in patients with OC and none of the meta-analyses showed that addition HIPEC to surgery was associated with a worse treatment outcome compared to surgery alone. Positive effect on treatment outcome was found more common in first-line treatment than recurrent disease. Positive effect on treatment outcome was more common in first-line treatment (especially during interval debulking surgery) than recurrent disease. HIPEC efficacy can be affected by patients' characteristics (BRCA status, platinum sensitivity), cytostatic type and dose, intensity of hyperthermia and peritoneal flow characteristics. Apart from strict cytotoxic effect, HIPEC can induce anti-cancer immune response. Although factors confounding HIPEC efficacy are not well-defined, survival improvement, related to addition HIPEC to surgery in OC, was observed. Future studies should focus on determining a subgroup of patients, who benefit from HIPEC. This will contribute to the unification of European and American recommendations.

Evaluating Disease-specific Survival Prediction of Risk Stratification and TNM Systems in Differentiated Thyroid Cancer.

Many countries have national guidelines for the management of differentiated thyroid cancer (DTC), including a risk stratification system to predict recurrence of disease. Studies whether these guidelines could also have relevance, beyond their original design, in predicting survival are lacking. Additionally, no studies evaluated these international guidelines in the same population, nor compared them with the TNM system. Therefore, we investigated the prognostic value of 6 stratification systems used by 10 international guidelines, and the TNM system with respect to predicting disease-specific survival (DSS). We retrospectively studied adult patients with DTC from a Dutch university hospital. Patients were classified using the risk classification described in the British, Dutch, French, Italian, Polish, Spanish, European Society of Medical Oncology, European Thyroid Association, the 2009 and 2015 American Thyroid Association (ATA) guidelines, and the latest TNM system. DSS was analyzed using the Kaplan-Meier method, and the statistical model performance using the C-index, Akaike information criterion, Bayesian information criterion, and proportion of variance explained. We included 857 patients with DTC (79% papillary thyroid cancer, 21% follicular thyroid cancer). Median follow-up was 9 years, and 67 (7.8%) died because of DTC. The Dutch guideline had the worst statistical model performance, whereas the 2009 ATA/2014 British guideline had the best. However, the (adapted) TNM system outperformed all stratification systems. In a European population of patients with DTC, of 10 international guidelines using 6 risk of recurrence stratification systems and 1 mortality-based stratification system, our optimized age-adjusted TNM system (8th edition) outperformed all other systems.

Evaluation of vaginal brachytherapy for treating early-stage endometrial cancer according to the European Society of Medical Oncology 2020 risk stratification.

The aim was to evaluate vaginal brachytherapy (VB) after surgery in early-stage endometrial cancer. The patients with Stage I-II endometrial adeno-cancer operated between 1998 and 2018 and whose adjuvant therapies had been arranged were evaluated retrospectively. A total of 618 patients were enrolled. In 409 patients in the low-risk group, the vaginal, pelvic recurrence, and distant metastasis rates were found to be higher in the VB group. When the results of 112 patients in the intermediate-risk group were evaluated, there was no statistically significant difference between the vaginal, pelvic recurrence, and distance metastasis rates. In 89 patients in the intermediate-high risk group, vaginal recurrence rates were 0%, 4.8%, 0%, and 25% for VB, external beam radiotherapy, combination radiotherapy, and the follow-up groups, respectively (p=0.010), and pelvic recurrence rates were found to be 18.2%, 0%, 1.9% and 0% (p=0.036). Distant metastasis rates were 0%, 0%, 9.6% and 0% (p=0.229). When the overall survival in all groups was examined, no significant difference was found between the groups. In conclusion, no adjuvant treatment is a proper approach for low-risk patients. Brachytherapy can be considered a suitable option for the intermediate risk group. Combined treatments instead of VB in the high-intermediate risk group would be preferred in terms of local control.

2022 European Society for Medical Oncology: Meeting highlights.

2022 European Society for Medical Oncology: Meeting highlights.

United Arab Emirates Population-Based Acute Leukaemia Registry: Acute Lymphoblastic Leukaemia Real-World Data

Population-based registries may provide data useful for clinical decisions in patients' populations not well presented by clinical studies, which is essential to establish recommendations for the management of patients in the real world. The aim of the first Sheikh Shakhbout Medical City (SSMC) ongoing acute leukaemia registry is to obtain information about the demography, clinical presentation, genetic markers, risk stratification and disease response of patients with diverse ethnicities and backgrounds .The registry includes newly diagnosed adults with acute leukaemia, admitted to SSMC from June 2021 onward. SSMC acute leukaemia registry is an observational retrospective and prospective study. Electrical medical records were used to collect data, and coding was used for each variable based on the 2017 European leukaemia network (ELN) and the 2016 European society for medical oncology (ESMO) clinical practice guidelines. A total of 41 patients were registered between June 2021 and May 2022. Eighteen patients with Acute Lymphoblastic leukaemia/Lymphoma (ALL) and 1 patient mixed-lineage leukaemia (MLL). Of the 18 patients with ALL, 6 patients with T-cell ALL, one of them with antecedent Chronic myeloid leukaemia (CML), and 12 patients with B-cell ALL. Seventy four percent of patients are males (n=14) and 26% (n=5) are females, 58% (n=11) are younger than 40 years of age, and 42% (n=8) are between 40 and 65 years old, with median age of 37 years at the time of diagnosis. Forty Seven percent of patients are Arabs, 26% are South Asian, 11% are Southeast Asian, 11% are African, and 5% are from other ethnicities (Table 1). Seventy four percent (n=14) of patients have adverse prognosis as per Hoelzer D et al., (2016). Of the 12 patients with B-cell ALL, 5 patients with Philadelphia chromosome-positive, accounts for 41% of patients which is higher compared to the 31% reported percentage in other clinical trials (Gupta R et al., 2018), 3 patients with Philadelphia-like chromosome positive, accounts for 25% of patients which is within the reported percentage range in other trial canters (Hoelzer D et al., 2016; National Comprehensive Cancer Network [NCCN], 2022) Induction regimens included paediatric protocols (n=3), hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose methotrexate, and cytarabine (HyperCVAD) (n=14), and 2 patients did not receive induction chemotherapy due to refusal of therapy and loss of follow up. As per the NCCN (2022), 6 patients achieved complete remission (CR) post induction,4 of which have negative minimal residual disease (MRD), 1 patient has positive MRD and 1 patients has failed MRD test. One patient achieved CR with incomplete hematologic recovery (CRi), 4 patients had partial remission, 2 patients were evaluated as treatment refractory, and 6 patients had no disease assessment post induction due to death or loss of follow up. Waca SSMC is one of the major leukaemia centres in Abu Dhabi, United Arab Emirates (UAE), where petroleum and natural gas are the main industry. UAE population consists of mixed ethnicities with different socioeconomic backgrounds where consanguinity is common and air pollution exposure at home countries is a big possibility. Despite the fact that our patient population is small, and statistically significant analysis might not be possible at this stage, we believe that our patient population demographics and genetic markers are not well-reflected in the standard guidelines. With longer observation and time the SSMC acute leukaemia registry promises to provide interesting data that may shed important input for better treatment algorithms. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

United Arab Emirates Population-Based Acute Leukaemia Registry: Acute Myeloid Leukemia Real-World Data

Population-based registries may provide data useful for clinical decisions in patients' populations not well presented by clinical studies, which is essential to establish recommendations for the management of patients in the real world. The aim of the first Sheikh Shakhbout Medical City (SSMC) ongoing acute leukaemia registry is to obtain information about the demography, clinical presentation, genetic markers, risk stratification and disease response of patients with diverse ethnicities and backgrounds .The registry includes newly diagnosed adults with acute leukaemia, admitted to SSMC from June 2021 onward. SSMC acute leukaemia registry is an observational retrospective and prospective study. Electrical medical records were used to collect data, and coding was used for each variable based on the 2017 European leukaemia network (ELN) and the 2016 European society for medical oncology (ESMO) clinical practice guidelines. A total of 41 patients were registered between June 2021 and May 2022, 18 patients with acute myeloid leukaemia (AML), 3 acute promyelocytic leukaemia (APL) , and 1 blastic plasmacytoid dendritic cell neoplasm (BPDCN). Seventy three percent (n=16) of patients are males, and 27% (n=6) are females. Eighteen percent of patients (n=4) are older than 65 years of age, 2 of them with antecedent myelodysplastic syndrome. About 54% of patients are Arab, 32% are South Asian, and 14% are Southeast Asian (Table 1). Forty percent of patients with normal karyotype which is close to previously reported percentage in Grimwade D et al, MRC AML 10 Trial. Blood 1998. Though our patients median age is 47 years at time of diagnosis, according to the 2017 ELN molecular stratification, about 32% of our patient group have adverse prognosis, which is higher compared to other clinical trials including the ones with older patients population (Grimwade D et al, MRC AML11 trial. Blood 2001). Four patients are FLT3-ITD positive, accounts for 22% which is similar to the reported percentage in Papaemmanuil E et al, Genomic Classification and Prognosis in AML. N Engl J Med. 2016. Two patients are IDH1 positive, 1 patient is IDH2 positive, accounts for 5% compared to the reported 1% in Dohner H et al, Diagnosis and management of AML in adults. Blood. 2017 Jan. Seven patients have other abnormal Next generation sequencing (NGS) results, 2 patients have negative NGS and 6 patients have unknown cytogenetic risk group. Induction chemotherapy includes standard-dose cytarabine 100-200 mg/m2 continuous infusion x 7 days with idarubicin 12 mg/m2 x 3 days in 33% of patients with AML, single dose of gemtuzumab ozogamicin 3 mg/m2 in addition to standard-dose cytarabine 200 mg/m2 continuous infusion x 7 days with daunorubicin 60 mg/m2 x 3 days in 17% of patients, hypomethylating agents with or without venetoclax in 22% of patients, and 28% of patients were not treated for various reasons including death and refusal of treatment. The 3 patients with APL are low-risk (WBC count ≤10,000/mcL) as per Sanz MA et al, Management of APL. Blood. 2019 . All treated with all-trans retinoic acid (ATRA) 45 mg/m2 in two divided doses daily and arsenic trioxide (ATO) 0.15 mg/kg IV daily. The patient with BPDCN was treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with high-dose methotrexate and cytarabine. About 43% of patients achieved complete response (CR) or CR with incomplete hematologic recovery (CRi) post-induction as per the 2017 ELN guidelines. SSMC is one of the leukaemia centres in Abu Dhabi, United Arab Emirates (UAE), where petroleum and natural gas are the main industry. UAE population consists of mixed ethnicities with different socioeconomic backgrounds where consanguinity is common and air pollution exposure at home countries is a big possibility. Despite the fact that our patient population is small, and statistically significant analysis might not be possible at this stage, we believe that our patient population demographics and genetic markers are not well-reflected in the standard guidelines. With longer observation and time the SSMC acute leukaemia registry promises to provide interesting data that may shed important input for better treatment algorithms. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Role of Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma in the First Complete or Partial Remission: A Propensity Score-Matched Analysis

Background Consolidation with autologous stem cell transplantation (ASCT) was recommended for most responders to the initial peripheral T-cell lymphoma (PTCL) treatment. Evidence came primarily from retrospective studies affected by a selection bias between patients allocated to receive ASCT or not and a few prospective studies with no control groups (d'Amore F,2012; Ellin F, 2014). The National Comprehensive Cancer Network and the American Society for Transplantation and Cellular Therapy (ASTCT) recommend ASCT for patients with first-time complete remission (CR1). The European Society of Medical Oncology (ESMO) guidelines suggest that patients with first-time partial remission (PR1) could also be considered for ASCT (d'Amore F, 2015). However, the role of ASCT in patients with PTCL after CR1 or PR1 remains controversial. The COMPLETE study showed an insignificant tendency for better survival following ASCT in the PTCL with CR1 group (Park SI, 2016). The LYSA multicenter study investigated the effect of ASCT in patients with CR1 or PR1. Neither propensity score matching (PSM) nor Cox multivariate analysis supported the advantage of ASCT in upfront consolidation (Fossard G, 2018). However, well-designed randomized controlled trials to investigate the precise effect of ASCT in the front-line setting are lacking. Therefore, we aimed to investigate the efficacy of ASCT for PTCL with CR1 and PR1 by PSM analysis. Methods We pre-screened 8 826 patients with lymphoma admitted to Peking University, Cancer Hospital & Institute from January 1996 to November 2020. Patients with mature T/NK cell lymphomas were selected (n = 1 136). We excluded patients with NK/TCL or missing clinical data. Response assessment to the initial treatment was evaluated by 18F-FDG positron emission tomography/computed tomography (PET/CT) or CT using the Lugano criteria. We identified 685 patients with PTCL, of which 622 achieved CR1 or PR1. PSM was used to balance clinical indicators between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Results Among the 622 patients who underwent initial therapy, 272 (43.7%) achieved CR1, and 147 (23.6%) achieved PR1 after the treatment. After excluding 5 patients with subsequent unknown schemes following the initial treatment, 414 were included in the final analysis (ASCT, n = 73; non-ASCT, n = 341). With a median follow-up of 5.7 years for the entire cohort, long-term survival in the ASCT group was better than in the non-ASCT group (median EFS, 8.1 vs. 2.8 years, P = 0.002; median OS, 14.9 vs. 10.2 years; P = 0.007). The 5-year EFS and OS were 66.7% (95% CI, 56.0-79.4%) and 74.7% (95% CI, 64.1-87.0%) in patients with ASCT consolidation, and 26.6% (95% CI, 23.0-30.8%) and 43.6% (95% CI, 39.2-48.4%) in patients without ASCT. After PSM, the ASCT and non-ASCT groups were similar in their disease subtypes, LDH level, Ann Abor stage, and the response to the initial treatment. The survival advantage for ASCT (n = 46), as a consolidation procedure, over non-ASCT (n = 84; median EFS. 8.1 vs 2.7 years, P = 0.007; median OS, not reached vs 7.7 years; P = 0.022; Figure 1) was maintained even after PSM. For the entire cohort, ASCT was associated with better long-term survival than non-ASCT [hazard ratio (HR) for EFS, 0.46 (95% CI, 0.28-0.76), P = 0.003; HR for OS, 0.50 (95% CI, 0.31-0.84), P = 0.008)]. Subgroup analysis showed that patients at a higher risk based on International Prognostic Index (IPI) stratifications and advanced stages might benefit significantly from ASCT. Patients with angioimmunoblastic T-cell lymphoma (AITL) in the ASCT group appeared to show better survival than those in the non-ASCT group (EFS: HR, 0.26; 95% CI, 0.10-0.66; P = 0.005; OS: HR, 0.29; 95% CI, 0.12-0.74; P = 0.009). However, ASCT endowed no survival advantage for other PTCL subtypes. Conclusion ASCT could improve the long-term survival of responders to the initial treatment among patients with PTCL, especially those with AITL. However, the specific population that could benefit most from up-front ASCT needs to be characterized further. Figure 1. EFS (A) and OS (B) after propensity score matching in the ASCT and non-ASCT groups Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Case Report on a Chemotherapy Treatment to a SARSCOV2 PCR Positive, Non-Hodgkins Lymphoma Filipino Patient

SARSCOV2 causing the COVID-19 infection has spread to a pandemic scale and putting the vulnerable population at risk of infection such as those with malignancies. Cancer treatment remains to be controversial in this time of pandemic such that recommendations were either delay treatment, reduce hospital exposure, or to balance the risk of disease progression(e.g. malignancy) and acquiring the disease (COVID-19). Information on COVID-19 positive cancer patients receiving chemotherapy remains to be limited. Thus, this case is reported. The case is a 64 year old male, newly diagnosed, Non-Hodgkins lymphoma who presented with severe anemia and weight loss. He was diagnosed through the bone marrow findings of CD20, Ki67, BCL2 positive B cell Non-Hodgkins lymphoma, NOS. He underwent induction chemotherapy with Prednisone, Cyclophosphamide and Vincristine. Thereafter he diagnosed to have COVID-19 infection, moderate. He remained to be PCR positive but with noted negative IgM Antibody. He showed signs of worsening anemia thus was given succeeding chemotherapy while admitted in the COVID unit of the hospital. Malignancy in general poses greater risk of severe infection with COVID-19 and possibly a worse outcome.8 The decision to proceed with chemotherapy treatment at the time when cases in the Philippines were not clear due to few testing capacity in the different institutions was based on the symptomatic persistence of severe anemia and weight loss as well as reduction in the functional capacity of the patient. The focus of efforts of oncologists and hematologists as recommended by their respective societies was on the reduction of the possibility of acquiring COVID-19 infection. There is paucity of data among those patients who have been diagnosed with COVID-19 and was given chemotherapy. Although, several studies have shown that among patients with COVID-19 and cancer as co-morbidity, the mortality can reach as high as 21% to 33% or can present with severe type of infection. Recommendations given by National Cancer Center Network(NCCN), American Society of Clinical Oncology(ASCO), European Society for Medical Oncology(ESMO, National Institute for Health and Care Excellence(NICE), World Health Organization(WHO), and Center for Disease Control(CDC) consistently revolve around the shifting of follow-up consults via teleconsultation to reduce travel to the hospital, delay or reduction of immunosuppressive treatments if possible, careful and holistic, multidisciplinary individualized approach in chemotherapeutic treatment, and withholding chemotherapy once positive with SARSCOV2 PCR positive test. In this case, the patient remained to be asymptomatic, non-oxygen requiring but remained to be positive on his 3rd PCR test done (20 days from initial positive test). The infectious disease service considered this as a false positive test and only a reflection of SARSCOV2 RNA remnants in the patient's upper airway. The clinical presentation of this cancer patient to the COVID infection is contradictory to those seen in most studies reviewed. Based on the limited knowledge on the pathophysiology of COVID-19, hyperinflammatory response occur in a robust immune system that causes Systemic inflammatory response syndrome(SIRS) and cytokine storm or hypoinflammatory response leading to multiple secondary bacterial infection.10 But neither was seen in this case. It is therefore possible that details of the mechanism of COVID-19 infection and its association with co-morbidities (malignancy) to severity are yet to be elucidated. All of the knowledge that is learned in this time of pandemic stems from a continuous trial and error efforts of clinicians who, through a sound theoretical foundation, first hand clinical experience and outcome endlessly refine approaches to produce the best outcome for those who are infected with the virus, most importantly, to the vulnerable population, such as those who is burdened by malignancies and COVID-19 infection. The treatment of COVID-19 positive patients with hematologic malignancy should be individualized and should focus on the balance between disease severity and risk of worsening COVID-19 infection.

Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients with Renal Insufficiency: A Systematic Review and Meta-Analysis

Introduction: Renal insufficiency (RI) is a common feature of multiple myeloma (MM). The relative risk (RR) of disease progression or death in patients with RI was higher than those without. RI increases risk of early death and affects disease management in multiple ways in MM, as it may complicate treatment options and dosing, and render patients more susceptible to infections and prolonged hospitalizations. Therefore, there is an urgent need to figure out the most effective regimen to treat MM patients with RI. But according to our knowledge, no head-to-head trial or meta-analysis has been conducted to determine which regimen would be the best choice for those patients. Daratumumab, an IgG1κ human monoclonal antibody that targets CD38, has shown durable responses and a favorable safety profile in both heavily pretreated patients with relapsed/refractory MM (RRMM) as monotherapy or combined with other agents and patients with newly diagnosed MM (NDMM). Pharmacokinetic analyses suggest that no clinically significant differences were found in patients with normal or impaired renal function following exposure to daratumumab, but the available data on efficacy of MM patients with RI are limited. Thus, to generate the efficacy evidence in MM patients with RI of Daratumumab among currently available agents, we conduct this meta-analysis regarding comparative efficacy of treatments for multiple myeloma patients with renal insufficiency, and compare those of MM with RI with those of MM without RI. Methods and methodology: A comprehensive literature search on 3 databases (PubMed, EMBASE and Cochrane Library) was performed from inception of each database to March 30, 2022. In addition, we performed a search of the gray literature through manual hand search of conference abstracts and proceedings of the American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Myeloma Network and European Society for Medical Oncology from 2018 to 2022. A total of 8 studies including 4576 patients were included in this study. 2388 were in the Dara group and 2188 were in the control group. HR of OS, PFS and MRD negativity rate were computed by using a fixed-effect model by RevMan v.5.4. Results: Among the included studies which conducted in the NDMM patients, MAIA and ALCYONE studies reported mature median OS data. The meta-analysis of these two studies showed the addition of Daratumumab to backbone regimens in transplant-ineligible NDMM with RI significantly improved the OS (pooled HR, 0.63; 95%CI, 0.48-0.82; P = .0007). Similarly, Daratumumab addition to backbone regimens in RRMM patients with RI decreased the risk of death (Pooled HR, 0.68; 95% CI, 0.51-0.92; P = .01). In the meta-analysis, the addition of daratumumab to backbone regimens in NDMM among patients with RI was associated with improved PFS (pooled HR, 0.46; 95%CI, 0.36-0.57; P < .00001). Similar results were seen for RRMM patients with RI (pooled HR, 0.46; 95% CI, 0.37-0.58; P < .00001). 2 studies (Alcyone, Cassiopeia) conducted in NDMM patients had subgroup analysis of MRD- rate in MM with RI, the meta-analysis showed that the addition of Daratumumab to backbone regimens could lead to higher MRD- rate (Risk ratio, 1.72; 95% CI, 1.45-2.06; P＜.00001). Meta-analysis conducted among patients with non-RI showed that addition of Daratumumab to standard of care treatment significantly improved the OS (NDMM: pooled HR, 0.64; 95% CI, 0.50-0.82; P =.0005; RRMM: pooled HR, 0.73; 95% CI, 0.60-0.89; P = .001) and PFS (NDMM: pooled HR, 0.57, 95% CI, 0.47-0.69; P＜.00001; RRMM: pooled HR, 0.43; 95% CI, 0.37-0.49; P＜.00001) in both NDMM and RRMM. And MRD- rate was improved as well (NDMM: Risk ratio, 1.58; 95% CI, 1.36-1.83; P＜.00001). Through the test for outcomes of MM patients with RI and non-RI, the result showed that the addition of Daratumumab to the backbone regimens can improve the OS (NDMM: p=0.93; RRMM: p=0.70), PFS (NDMM: p=0.28; RRMM: p=0.55) and MRD- rate (NDMM: p=0.45) of MM patients with RI and non-RI in both NDMM and RRMM to the same extend. Discussion: This study suggests that the addition of Daratumumab to the backbone regimens can lead to longer OS, PFS and achieve higher MRD- rate among patients with RI and non-RI in the context of newly diagnosed and relapsed or refractory disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Off-label despite high-level evidence: a clinical practice review of commonly used off-patent cancer medicines

Off-label use of medicines is generally discouraged. However, several off-patent, low-cost cancer medicines remain off-label for indications in which they are commonly used in daily practice, supported by high-level evidence based on results of phase III clinical trials. This discrepancy may generate prescription and reimbursement obstacles as well as impaired access to established therapies. A list of cancer medicines that remain off-label in specific indications despite the presence of high-level evidence was generated and subjected to European Society for Medical Oncology (ESMO) expert peer review to assess for accountability of reasonableness. These medicines were then surveyed on approval procedures and workflow impact. The most illustrative examples of these medicines were reviewed by experts from the European Medicines Agency to ascertain the apparent robustness of the supporting phase III trial evidence from a regulatory perspective. A total of 47 ESMO experts reviewed 17 cancer medicines commonly used off-label in six disease groups. Overall, high levels of agreement were recorded on the off-label status and the high quality of data supporting the efficacy in the off-label indications, often achieving high ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores. When prescribing these medicines, 51% of the reviewers had to implement a time-consuming process associated with additional workload, in the presence of litigation risks and patient anxiety. Finally, the informal regulatory expert review identified only 2 out of 18 (11%) studies with significant limitations that would be difficult to overcome in the context of a potential marketing authorisation application without additional studies. We highlight the common use of off-patent essential cancer medicines in indications that remain off-label despite solid supporting data as well as generate evidence on the adverse impact on patient access and clinic workflows. In the current regulatory framework, incentives to promote the extension of indications of off-patent cancer medicines are needed for all stakeholders.

Endometrial cancer risk factors, treatment, and survival outcomes as per the European Society for Medical Oncology (ESMO) - European Society of Gynaecological Oncology (ESGO) - European Society for Radiotherapy and Oncology (ESTRO) risk groups and International Federation of Gynecology and Obstetrics (FIGO) staging: An experience from developing world.

There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGO-ESTRO and their recommendations for adjuvant treatment have redefined the management protocols. In this retrospective analysis, the outcomes are assessed in the light of the new risk groups and FIGO staging. One hundred and two patients of endometrial cancer reporting to the Department of Radiation Oncology from 2015 to 2019 were analysed retrospectively. Patients were stratified as per the ESMO-ESGO-ESTRO risk groups and FIGO staging. Patients were analysed for demographic profile, histopathology details, FIGO stage, treatment modalities received as per the ESMO-ESGO-ESTRO risk groups and the outcomes in terms of disease free survival and overall survival. A total of 102 patients were analysed. The mean age at presentation was 57.7 years. Seventy four percent (74.41%) were stage I patients, 14.7 % were stage II, 8.8% were stage III and remaining 2% were stage IV. The mean disease free survival for the patients in FIGO stage I, II, III and IV were found to be 63.5 (59.9 - 67) months, 60.5 (54.2 - 66.9) months, 30.9 (21.5 - 40.2) months and 15.4 (7.8 - 23.0) months respectively. The 5-year overall survival of patients in Stage I was 90.3%. The 3-year mortality of Stage III patients was 58.3%. While there was no mortality observed among Stage II patients, none of the Stage IV patient survived beyond 20 months. The 5-year disease-free survival for patients in Low Risk (LR) group, Intermediate Risk (IR) group and High Risk (HR) group was found to be 91.3%, 90% and 87% respectively. None of the patient in High Intermediate Risk (HIR) group experienced progression of disease and 33.3% patients in advanced group were disease free at 2 years follow-up. The multivariate analysis showed that lymph node involvement is significantly associated with disease-free (p=0.03) and overall survival (p=0.04). Even in the developing world, majority of patients present in early stage with survival outcomes comparable to the West. FIGO stage and lymph node involvement continue to be the most important prognostic markers for disease outcomes.

Early endometrial carcinoma: Experience and outcomes.

Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome. Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used. Our patients had a median age of 60 years (range 32-93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%. The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

ESMO Designated Centres of Integrated Oncology and Palliative Care (ESMO DCs): education, research and programme development survey

The European Society for Medical Oncology (ESMO) Designated Centres (DCs) of Integrated Oncology and Palliative Care is an incentive programme established in 2003 aiming to improve the integration of oncology and palliative care services provided by oncologists and oncology centres worldwide. Currently, the ESMO DCs programme has over 250 centres accredited from 54 countries worldwide, in all six world regions. To evaluate how ESMO can support centres to improve programme development, education and research and vice versa what each single centre can do to improve in these areas, we developed a survey which was shared with all active centres. Two hundred and seven ESMO DCs representing 44 countries were invited to participate. We used content analysis to identify response categories using a stepwise approach. After reviewing and coding all responses to each question separately, they were placed into categories, counted and labelled. Of the 207 centres that were invited to participate, 146 centres started the survey, representing 43 countries. Five overarching topics were identified. They included (i) joint events and educational activities; (ii) sharing of materials and defining common standards; (iii) sharing of experiences, scientific knowledge and expertise; (iv) research collaboration; and (v) ESMO support. Respondents were willing to support the ESMO DC community group in all topics and were also asking ESMO to support their centres in these issues in the future. The study showed that the ESMO DCs are willing to provide support to improve education, research and programme development. They are also eager to contribute and collaborate amongst each other, but also request ESMO to offer advice and help to improve these issues in the DCs. In the future, facilitation of joint research projects and development of arenas to share experiences, educational and programme developments, and other resources are to be explored and could be offered to the DCs worldwide.

Sentinel Lymph Node Biopsy in Cutaneous Melanoma, a Clinical Point of View.

Sentinel lymph node biopsy (SLNB) is a surgical procedure that has been used in patients with cutaneous melanoma for nearly 30 years. It is used for both staging and regional disease control with minimum morbidity, as proven by numerous worldwide prospective studies. It has been incorporated in the recommendations of national and professional guidelines. In this article, we provide a summary of the general information on SLNB in the clinical guidelines for the management of cutaneous malignant melanoma (American Association of Dermatology, European Society of Medical Oncology, National Comprehensive Cancer Network, and Cancer Council Australia) and review the most relevant literature to provide an update on the existing recommendations for SLNB.

European Society of Medical Oncology (ESMO) 2022: Thyroid Cancer Updates from the Annual Convention

European Society of Medical Oncology (ESMO) 2022: Thyroid Cancer Updates from the Annual Convention

European Society of Medical Oncology (ESMO) - 2022 Annual Congress. Paris/Virtual - September 9-13, 2022

European Society of Medical Oncology (ESMO) - 2022 Annual Congress. Paris/Virtual - September 9-13, 2022