Oncology Meetings Research Articles

Cyclin-dependent kinase 4 and 6 inhibitors in combination with neoadjuvant endocrine therapy in estrogen receptor-positive early breast cancer: a systematic review and meta-analysis.

The combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine treatment has benefited patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer; however, its effects in the neoadjuvant setting for ER + /HER2- early breast cancer (EBC) are unclear. Systematic searches were performed in PubMed, Embase, Cochrane Library, and major oncological meetings for trials of CDK4/6 inhibitors plus neoadjuvant endocrine treatment (NET) vs. NET/neoadjuvant chemotherapy (NACT) alone up to January 30, 2021. We assessed the efficacy of CDK4/6 inhibitors plus NET vs. NET/NACT alone in ER + /HER2- EBC. Six studies that included 803 patients treated with CDK4/6 inhibitors plus NET vs. NET/NACT alone were used. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased the complete cell cycle arrest (CCCA) rate (OR, 9.00; 95% CI, 5.42-14.96; P < 0.001). Nonsignificant differences between CDK4/6 inhibitors and NET/NACT alone occurred in the preoperative endocrine prognostic index (PEPI)-0 rate (OR, 1.13; 95% CI, 0.59-2.18; P = 0.71), pathological complete response (pCR) rate (OR, 0.75; 95% CI, 0.13-4.29; P = 0.74), objective response rate (ORR) (OR, 0.70; 95% CI, 0.21-2.29; P = 0.55), and disease control rate (DCR) (OR, 1.16; 95% CI, 0.47-2.89; P = 0.74). CDK4/6 inhibitors plus NET indicated a high risk of neutropenia (OR, 56.43; 95% CI, 15.76-202.11; P < 0.001) as an adverse effect (AE) and elevated alanine aminotransferase (ALT) level (OR, 15.30; 95% CI, 2.02-115.98; P = 0.008) as grade 3/4 AEs. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased CCCA rate in ER + /HER2- EBC patients. CDK4/6 inhibitors plus NET did not substantially improve the PEPI-0 rate, pCR rate, ORR, or DCR. The combination increased the risk of neutropenia and elevated ALT levels. In the neoadjuvant setting, addition of CDK4/6 inhibitors to NET may be an option for treating ER + /HER2- EBC.

Pathologic Complete Response in Urothelial Carcinoma Patients Receiving Neoadjuvant Immune Checkpoint Inhibitors: A Meta-Analysis.

Background. Immune checkpoint inhibitors (ICIs) have been evaluated as neoadjuvant treatment in urothelial carcinoma (UC) patients, with these agents reporting encouraging pathologic complete response (pCR) rates. Herein, we performed a systematic review and meta-analysis aimed at evaluating the incidence of pCR in UC patients treated with neoadjuvant ICI. Moreover, we investigated the impact of PD-L1 expression in this patient population, exploring the possible role of PD-L1 status as predictive biomarker. Materials and Methods. We retrieved all the relevant trials through PubMed/Medline, Cochrane Library and EMBASE; moreover, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible trials assessed pre-operative ICI in UC patients. Results. Our meta-analysis has highlighted a pooled pCR rate of 36.6% in the overall population; interestingly, pCR was higher in PD-L1 positive compared with PD-L1 negative UCs (49.5% versus 35.1%, respectively). Conclusions. Positive signals emanating from neoadjuvant immunotherapy should encourage the scientific community to persist in the long road toward finding more effective treatments for UC patients.

Using guideline-based clinical decision support in oncological multidisciplinary team meetings: A prospective, multicenter concordance study.

BackgroundMultidisciplinary team meetings formulate guideline-based individual treatment plans based on patient and disease characteristics and motivate reasons for deviation. Clinical decision trees could support multidisciplinary teams to adhere more accurately to guidelines. Every clinical decision tree is tailored to a specific decision moment in a care pathway and is composed of patient and disease characteristics leading to a guideline recommendation.ObjectiveThis study investigated (1) the concordance between multidisciplinary team and clinical decision tree recommendations and (2) the completeness of patient and disease characteristics available during multidisciplinary team meetings to apply clinical decision trees such that it results in a guideline recommendation.MethodsThis prospective, multicenter, observational concordance study evaluated 17 selected clinical decision trees, based on the prevailing Dutch guidelines for breast, colorectal and prostate cancers. In cases with sufficient data, concordance between multidisciplinary team and clinical decision tree recommendations was classified as concordant, conditional concordant (multidisciplinary team specified a prerequisite for the recommendation) and non-concordant.ResultsFifty-nine multidisciplinary team meetings were attended in 8 different hospitals, and 355 cases were included. For 296 cases (83.4%), all patient data were available for providing an unconditional clinical decision tree recommendation. In 59 cases (16.6%), insufficient data were available resulting in provisional clinical decision tree recommendations. From the 296 successfully generated clinical decision tree recommendations, the multidisciplinary team recommendations were concordant in 249 (84.1%) cases, conditional concordant in 24 (8.1%) cases and non-concordant in 23 (7.8%) cases of which in 7 (2.4%) cases the reason for deviation from the clinical decision tree generated guideline recommendation was not motivated.ConclusionThe observed concordance of recommendations between multidisciplinary teams and clinical decision trees and data completeness during multidisciplinary team meetings in this study indicate a potential role for implementation of clinical decision trees to support multidisciplinary team decision-making.

Evolving Immuno-Chemotherapeutic Paradigms in Esophageal and Gastric Cancers

Esophageal (EC) and gastric (GC) cancers represent severe global health issues. Within the last 18 months, the standard of care has significantly evolved for the first-line setting of advanced EC and GC within the field of human epidermal growth factor receptor 2 (HER2)-negative and HER2-positive patients. The breakthrough concepts for clinical practice of immune checkpoint inhibitors (ICIs) plus chemotherapy in both fields were presented at major oncology meetings over the last 2 years. This review summarizes the latest results on when and how to use the new combinations and highlights the unsolved issues in this new era.

Update on optimal management for pancreatic cancer: expert perspectives from members of the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty

ABSTRACT Introduction Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localized and advanced pancreatic cancer and offers an expert opinion on current best practice. Areas covered For patients with localized disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable, and locally advanced disease. Advances in metastatic disease are discussed including cytotoxic chemotherapy, targeted therapies, and the role of genomic testing to identify patients with molecular alterations. Reviewed literature included journal publications, abstracts presented at major international oncology meetings, and ongoing clinical trials databases. Expert opinion Pancreatic cancer is a devastating diagnosis and despite recent advances has a very poor prognosis. Only a minority of patients, 20%, are diagnosed with potentially curable disease. The shifting paradigm toward neoadjuvant therapy may improve resectability and survival rates; however, robust evidence is required. Thus far, there has only been limited progress in advanced stage disease. Genomic testing may potentially identify more treatment targets although limited to small subgroups.

Treatment options for advanced urothelial cancer after progression on chemotherapy and immune checkpoint inhibitors: a literature review.

ObjectiveTo describe the current treatment landscape in advanced urothelial cancer (aUC)/metastatic urothelial cancer and in particular to review the relevant literature highlighting recent advances in the treatment of patients with aUC after progression on chemotherapy and immune checkpoint inhibitor (ICI).BackgroundaUC is a very aggressive disease with poor outcomes. Over the past several years, its treatment landscape has seen significant advances with the approval of ICI and targeted agents, which have led to improved outcomes. The current standard of care for most patients with aUC involves platinum-based chemotherapy followed by ICI after progression or as switch maintenance therapy (if no progression after chemotherapy). Treatment of patients following progression on ICI is more challenging, but novel therapies have been approved, such as erdafitinib for tumors with fibroblast growth factor receptor 2 (FGFR2) or FGFR3 activating mutation or fusion (can also be used following progression on platinum-based chemotherapy), enfortumab vedotin (EV) and sacituzumab govitecan (SG) in an unselected patient population. Many other trials in this space are currently ongoing and other promising agents may also potentially become available in the future.MethodsNarrative overview of the recent literature relevant to the treatment of advanced/metastatic urothelial cancer following progression on chemotherapy and ICI was undertaken. Relevant literature was obtained from review of computerized databases including pubmed.gov and proceedings of major conferences including American Society of clinical Oncology (ASCO) Meetings, GU ASCO Symposia and European Society of Medical Oncology (ESMO) Meetings.ConclusionsIn this narrative review, we highlight the current dynamic treatment landscape in aUC, emphasizing the recent important developments and a few examples of ongoing clinical trials. In particular, we focus on therapy options available following progression on platinum-based chemotherapy and ICI, a treatment space where until recently there had been no FDA-approved treatment options. The recent pivotal trials of antibody drug conjugates (ADCs) that led to FDA approvals in this space are highlighted, as are other agents currently in development. We conclude by discussing future directions and ongoing challenges in this evolving disease space.

Impact of the first COVID-19 wave on surgical training in Flanders: are we losing competence?

Background The COVID-19 pandemic has tremendously impacted the healthcare system and residency programs worldwide. Surgical residents were redeployed to COVID-19 units, whereas education and scientific didactics were reduced. The aim of this study is to identify the impact of COVID-19 on Flemish surgical residents’ education, personal life and volume of performed surgeries. Methods A cross-sectional retrospective survey on educational and personal impact during the first COVID-19 wave was administered anonymously to all surgical residents in Flanders. A quantitative comparison of performed surgeries during this period and the same period a year earlier was conducted. Results A total of 193 surgical residents (46%) completed the survey. 63% of residents were no longer admitted to multidisciplinary oncologic meetings and 107 (55%) residents had no longer any scientific theoretical meetings at all. Almost one in two residents (46%) indicated more than 50% reduction in time in the operating theater and one in three (31%) residents were involved in care for COVID-19 positive surgical patients. Seventy-eight percent of the residents experienced a negative impact on their surgical training and 41% experienced a negative influence on their private situation. Performed surgical cases during the COVID-19 period were on average 40% less for second, third- and fourth-year residents. Conclusion Surgical residents perceived a high negative impact on personal and professional lives during the start of the COVID-19 pandemic in Flanders. Education and training programs were cancelled and volume of performed surgeries decreased tremendously. Policymakers and surgical program coordinators should ensure surgical education during further evolution of this and future pandemics.

The subjective interpretation of negative trial results during oral plenary presentations

<h3>Objectives:</h3> Oral presentations of phase 3 randomized controlled trials (RCTs) at oncology meetings often do not undergo peer review; this may lead to conclusions that do not reflect the primary results of the study. For example, the presentation may include a positive conclusion despite a negative trial result. Presentations at medical society meetings may have significant impact on the oncology community. The purpose of this study is to quantify and categorize not-negative conclusions made in oral plenary presentations of phase 3 RCTs for gynecologic malignancies. <h3>Methods:</h3> Abstracts related to oral presentations of phase 3 RCTs at the Society of Gynecologic Oncology's Annual Meetings on Women's Cancer between 2005-2020 were reviewed. Studies with a primary endpoint of overall survival (OS) or progression free survival (PFS) and with a formally negative primary endpoint were included. Abstract conclusion sentences were classified as negative or not-negative. Trials with formally negative results were categorized based on the type of not-negative conclusions: 1) positive subgroup emphasis, 2) positive secondary endpoint emphasis, 3) emphasis on better numerical outcome despite nonsignificant p-value, 4) noninferiority interpretation of negative superiority trial. Studies with negative results and not-negative conclusions were compared to respective published manuscripts if available. The results and conclusion from the manuscript were compared to quantify and categorize not-negative conclusions. <h3>Results:</h3> Oral presentations of 61 phase 3 RCTs met inclusion criteria. Of these, 22 had a formally negative primary PFS or OS endpoint, of which 6/22 (27%) presented a not-negative conclusion. There was a higher proportion of not-negative conclusions among negative trials in more recent years, with 50% (5/10) of abstracts from 2015-2020 including not-negative conclusions, vs just 8.3% (1/12) in studies from the preceding decade 2005-2014 (p=0.03; Figure 1). Authors emphasized a positive subgroup in 4/6 studies and a positive secondary endpoint in 1/6 studies. A numerically better outcome in the experimental arm was highlighted in 2/6 studies despite a nonsignificant p-value, and 1/6 studies made a non-inferiority interpretation of a negative superiority trial. Of 21 studies with formally negative results, 56% (5/9) for-profit studies had not-negative conclusions, whereas 8.3% (1/12) non-profit studies had not negative conclusions (p=0.02). Published manuscripts were available for 3/6 not-negative studies, all similarly incorporating not-negative conclusions despite negative results. <h3>Conclusions:</h3> Since 2005, 27% of RCTs presented at SGO made not-negative conclusions despite formally negative results, with a majority emphasizing a positive subgroup and funded by for-profit organizations. These results further emphasize the importance of presenters' accurate portrayal of results and attendees' attention to bias during presentations.

Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials

BackgroundRecent years have witnessed the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combination therapies with immune checkpoint inhibitors. Herein, we conducted an up-to-date and comprehensive meta-analysis including recently published data of phase III clinical trials evaluating immune-based combinations in mRCC. MethodsWe retrieved all the relevant trials published from 15th June 2008 to 24th February 2021, evaluating immune-based combinations in treatment-naïve mRCC through PubMed/MEDLINE, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included overall survival (OS), progression-free survival (PFS), complete response (CR) rate, and overall response rate (ORR). Hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS, and odds ratios (ORs) and 95% CIs for CR rate and ORR, were extracted. ResultsOverall, 6 phase III studies involving 5175 treatment-naïve mRCC patients were available for the meta-analysis (immune-based combinations, n = 2576; sunitinib, n = 2597). According to our results, the use of immune-based combinations decreased the risk of death by 26% (HR 0.74, 95% CI 0.67–0.81, P < 0.001); similarly, a PFS benefit was observed (HR 0.68, 95% CI 0.54–0.85, P = 0.001). In addition, immune-based combinations showed better CR rate and ORR, with ORs of 3.04 (95% CI 2.31–3.99, P = 0.001) and 2.53 (95% CI 1.77–3.62, P < 0.03), respectively. ConclusionsThe results of our meta-analysis confirm the clinical benefit provided by immunotherapy combinations, with CR rate more than tripled in mRCCs receiving immune-based combinations. Further studies in real-world setting are warranted to validate the findings of our meta-analysis, the most updated to systematically evaluate immune-based combinations in mRCC.

Abstract 605: Evidence that a wide variety of cancers may use the progesterone induced blocking factor protein to escape immune surveillance as evidenced by significant palliation following treatment with progesterone receptor antagonists in advanced metastatic treatment resistant cancers

Abstract A search of the literature and abstracts from national oncology meetings was conducted to determine what types of human cancers have been reported to show some type of palliative benefit from treatment with progesterone (P) receptor antagonists. Though the original concept was to try P receptor antagonists for cancers known to be associated with the classic nuclear P receptor, recent data suggest that the real beneficial target is a membrane P receptor that helps produce a unique immunomodulatory protein called the progesterone induced blocking factor (PIBF) that inhibits natural killer (NK) cells and cytotoxic T cells in the tumor microenvironment and thus may allow cancer cells to metastasize. The following human cancers known to be associated with the classic nuclear receptor that have responded to either the P receptor modulator mifepristone or onapristone, include breast, uterine, ovarian, and prostate cancer. Human cancers not associated with the classic nuclear P receptor that have demonstrated significant palliative benefits and/or increased longevity following P receptor modulator therapy include colon, thymic cell epithelial cancer, transitional cell carcinoma of the renal pelvis, leiomyosarcoma, pancreatic carcinoma, malignant fibrous histiocytoma, glioblastoma multiforme grade IV, renal cell carcinoma, fibrous osteosarcoma, small cell lung cancer, non-small cell lung cancer (including those negative for tumor markers, or those positive for PD-1, or positive for the EGFR mutation). The wide variety of very advanced cancers that have responded to the P receptor modulators as evidenced by extension of a better quality of life despite the fact that they had progressed despite standard chemo or immunotherapy, is consistent with the concept that PIBF may be a protein needed by a large variety of cancers to advance or metastasize, and thus may provide a unique target to treat with P receptor modulators, and thus provide significant palliative benefit. In contrast to most anti-cancer agents, P receptor antagonists are extremely well tolerated, and are without serious risk of complications. Larger series are needed to determine the true beneficial effect of this type of therapy. Positive beneficial effects in case reports, at least provide the basis for selection of which cancers to evaluate in a larger series. Citation Format: Jerome H. Check, Diane Check, Carrie Wilson. Evidence that a wide variety of cancers may use the progesterone induced blocking factor protein to escape immune surveillance as evidenced by significant palliation following treatment with progesterone receptor antagonists in advanced metastatic treatment resistant cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 605.

Incremental Financial and Health-Related Burden of Novel Drugs Used in the Treatment of Relapsed and/or Refractory Multiple Myeloma (RRMM): A Meta-Analysis of Phase III Randomized Controlled Trials (RCTs)

Background:The remarkable progress in the outcomes of RRMM in the last 2 decades with the introduction of novel therapies have come with significant additional cost and adverse events (AEs). We quantified the incremental efficacy, AEs, and cost of newly approved anti-RRMM drugs by conducting a meta-analysis of pivotal phase III Randomized Controlled Trials (RCTs) used for registration.Methods: A systematic search of MEDLINE, SCOPUS and Cochrane databases was performed to identify RCTs leading to approvals of new agents for the treatment of RRMM from January 1, 1999 to July 1, 2017. Abstracts presented within the last four years at major hematology and oncology meetings were also identified. Hazard Ratios (HR) for Progression free Survival (PFS), Overall survival (OS), and Odds Ratios (OR) for all grade III/ IV AEs along with the respective 95% Confidence Intervals (CI) reported in the included studies were weighed using a generic inverse variance approach and were pooled using random effects model meta-analyses using RevMan 5.3 software. Incremental costs were calculated from 1) drug prices listed in Micromedex Redbook and 2) costs of management of AEs and health services costs based on published literature (adjusted for inflation to match 2017-US dollar value) for experimental compared to control arms.Results: Sixteen RCTs (n=8,683) involving 14 different treatment options qualified for inclusion (Table 1). Pooled analyses demonstrated a significant improvement in OS (HR 0.74; 95% CI: 0.62-0.89;p=0.002) and PFS (HR 0.55; 95% CI 0.48-0.64; p<0.00001) with the use of newly approved drugs or combinations compared to control arm. However, there was substantial increase in the risk of adverse events with the use of new-targeted agents and combination compared to the controls (OR for Grade III-IV toxicities 1.56, 95% CI: 1.29-1.88, p <0.00001). (Fig 1). There was no difference in treatment discontinuation and toxic deaths between the two groups. The median incremental drug price for experimental agents was $ 13,588/patient/month compared to the control arm. The new agents or combinations led to incremental cost of care by a median of $ 133,914/patient/month.Conclusion: Despite improvements in efficacy, newly approved drugs for RRMM are associated with increased rates of AEs, and add exponentially to financial burden, exceeding by far the acceptable willingness-to-pay threshold of most developed countries. Toxicities and costs are highest for immunomodulators and are likely to increase when the agents are used in unselected populations after the approvals leading to heavier health-related and financial burden to society. Strategies to lower cost of novel therapies, and better predictive tools to select patients are imperative for sustainability of RRMM treatments. [Display omitted] DisclosuresDhakal:Celgene: Honoraria. Chhabra:Cardinal Health: Honoraria; Incyte: Honoraria. Hari:Janssen: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy; Sanofi: Honoraria, Research Funding.

Immunotherapy era in the treatment of small cell lung cancer.

Small cell lung cancer (SCLC) is differentiated from non-small cell lung cancers with its histological and morphological features, rapid response to chemotherapy, and recurrence in a short time after treatment is discontinued. Platinum plus etoposide chemotherapy combination has been used as a standard treatment, and no new drug has been found for more than 30years in this disease. In research, the targeted pathways that may affect survival have not been identified yet. During the second half of the second decade of the 2000s, with immunotherapies that inhibit immune checkpoints, improvements in survival were achieved for the first time in treating SCLC after many years. Then a rapid increase was observed in chemotherapy plus immunotherapy combination studies in this field. Updated analyses of these studies were represented at international oncology meetings in 2020. Here, we reviewed immunotherapy studies conducted in patients with SCLC and the reflections on the daily practice.

First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis.

BackgroundImmune checkpoint inhibitors (ICIs) have become the standard of care for the first-line treatment of advanced non-small cell lung cancer patients (NSCLC), either as single agents or combined with chemotherapy. The evidence sustaining their role for poor performance status (ECOG PS ≥2) patients is limited.MethodsWe search PubMed and the proceedings of international oncology meetings to perform a systematic review to assess the outcomes poor PS NSCLC patients who received ICIs as first-line treatment. A meta-analysis included retrospective studies focusing on pembrolizumab monotherapy in PD-L1 ≥50% NSCLC. We reported the global objective response rate (ORR), disease control rate (DCR) and landmark progression-free and overall survival (PFS and OS, respectively) in ECOG PS ≥2 and 0–1 patients, respectively.ResultsForty-one studies were included in the systematic review. Thirty-two retrospective studies focused on pembrolizumab monotherapy in PD-L1 ≥50% cases. In total, 1,030 out of 5,357 (19%) of patients across 30 studies presented with a PS ≥2 at pembrolizumab initiation. In 18 studies with detailed clinical information, worse outcomes in poor PS compared to good PS patients were documented. The meta-analysis revealed that ORR and DCR within the PS ≥2 patient population were 30.9% and 41.5% respectively (55.2% and 71.5% in PS 0–1 patients). The rates of PFS (at 3, 6, 12 and 18 months) and OS (at 6, 12, 18 and 24 months) were approximately double in the good PS compared to the poor PS group of patients. In the three prospective trials where of ICIs in PS 2 populations, the diverse strictness in PS definition likely contributed to the differential outcomes observed. Six retrospective studies dealt with chemo-immunotherapy combinations.ConclusionsStill with limited prospective evidence sustaining the role of immunotherapy in previously untreated NSCLC with poor PS, 19% of patients in retrospective series dealing with pembrolizumab in PD-L1 ≥50% tumors had an ECOG PS ≥2. Clinical effort encompassing the definition of poor PS, of the factors conditioning it, and the development of dedicated treatment strategies is required to improve the outcomes in this patient population.

Impact of clinicopathological features on survival in patients treated with immune-based combinations for metastatic urothelial carcinoma: A meta-analysis of randomized clinical trials.

e16534 Background: Immune checkpoint inhibitors (ICIs) have recently revolutionized the treatment landscape of metastatic urothelial carcinoma (mUC). Nonetheless, little is known regarding the impact of clinicopathological features in this setting. We performed a meta-analysis aiming to evaluate the predictive value of ECOG-PS, age, gender, liver metastases, and histology in randomized controlled trials (RCTs) comparing ICI-based combinations versus chemotherapy in mUC patients. Methods: We retrieved all the relevant RCTs through PubMed/Med, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs comparing ICI-based combinations versus chemotherapy alone in mUC patients. The primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). All statistical analyses were performed using R studio software. Results: Overall, 1032 mUC patients were included in the analysis. Compared with chemotherapy, ICI-based combinations significantly decreased the risk of death in several clinicopathological subgroups, including no liver metastases (HR, 0.84; 95% CI, 0.74-0.95) and ECOG-PS 0 patients (HR, 0.84; 95% CI, 0.72-0.97). Similarly, ICI-based combinations were associated with prolonged OS in mUC patients who were &lt; 65 years old (HR, 0.82; 95% CI, 0.72-0.95), as well as in male (HR, 0.90; 95% CI, 0.82-0.99) and female patients (HR, 0.81; 95% CI, 0.68-0.97). Conversely, a non-statistically significant benefit was observed for chemotherapy alone in mUC patients with liver metastases (HR, 1.06; 95% CI, 0.86-1.31). Conclusions: According to our results, the magnitude of benefit of ICI-based combinations over chemotherapy in mUC was consistent across a number of clinicopathological subgroups, while a proportion of patients could respond to chemotherapy alone.Despite several limitations affect our analysis, we believe these results could guide in everyday treatment decision-making, also assisting in the design and interpretation of future clinical trials on ICIs in mUC.

Exploring the association between metastatic sites and androgen receptor splice variant 7 (AR-V7) in castration-resistant prostate cancer patients: A meta-analysis of prospective clinical trials

BackgroundThe Androgen Receptor Splice Variant 7 (AR-V7) has been associated with poor clinical outcomes in patients with castration-resistant prostate cancer (CRPC). Herein, we performed a meta-analysis aimed at systematically exploring the association between metastatic sites and AR-V7 expression in CRPC patients across prospective clinical trials. MethodsWe retrieved all the relevant prospective clinical trials through PubMed/Medline, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included metastatic sites (lymph node metastases, any site metastases, visceral metastases, and bone metastases) in AR-V7 positive and AR-V7 negative CRPC patients. Odds Ratios (ORs) and 95 % confidence intervals (CI) were calculated. ResultsOverall, 14 eligible prospective studies involving a total of 1944 CRPC patients (AR-V7 positive: 467; AR-V7 negative: 1477) were included in the analysis. According to our results, no differences between AR-V7 positive and AR-V7 negative CRPC patients were observed in terms of lymph node (OR 1.01; 95 % CI 0.49–2.09) and visceral metastases (OR 1.23; 95 % CI 0.89–1.71). Conversely, AR-V7 positive CRPC patients presented higher rate of any site metastases (OR 2.22; 95 % CI 1.58–3.12) and bone metastases (OR 2.03; 95 % CI 1.42–2.9) compared to AR-V7 negative subjects. ConclusionsThe results of this meta-analysis, the first in literature to be specifically focused on this topic so far, suggest that AR-V7 positivity may be associated with any site metastases and bone metastases; conversely, no association has been highlighted between AR-V7 expression and lymph node or visceral metastases. Although this meta-analysis should be interpreted with caution due to some limitations, our findings confirm that AR-V7 status could designate a unique and peculiar subtype of PC. Further studies aimed at improving and standardizing AR-V7 detection in clinical trials on CRPC patients are warranted.

Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: A systematic review and meta-analysis of randomized clinical trials.

Several randomized trials of neoadjuvant chemo-immunotherapy in early triple negative breast cancer (TNBC) have been recently reported, showing conflicting results. We systematically searched PubMed, Cochrane CENTRAL, Embase and key oncological meetings for trials of neoadjuvant chemo-immunotherapy in TNBC. The primary endpoint was pCR, with sub-analyses based on PD-L1 expression and risk of relapse. Five randomized trials enrolling 1496 TNBC patients were included. We observed a statistically significant association between PD1/PD-L1 blockade addition and pCR (SOR = 1.72, 95 %CI: 1.22-2.42). The benefit was significant in the PD-L1 positive subgroup (SOR = 1.65; 95 %CI: 1.06-2.57). pCR was also significantly increased in the high-risk subgroup (SOR = 2.39; 95 %CI: 1.09-5.22), when restricting to patients receiving an anthracycline-based NACT. We found no significant association between immunotherapy addition and toxicity, and no evidence of publication bias. The addition of PD1/PD-L1 blockade to NACT significantly improves pCR rates in TNBC patients, particularly in patients at high-risk of relapse.

Recent updates in systemic therapy of breast cancer: A brief narrative review

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in women globally. Systemic therapy of breast cancer has evolved rapidly in the past few years. In this brief review, we aim to summarize the potentially practice-changing recent updates in the management of breast cancer. We searched the PubMed database for randomized clinical trials for breast cancer treatment conducted over the past 2 years. In addition, abstracts and results of studies reported at major oncology meetings were evaluated. A total of 95 randomized clinical trials were included to prepare this review. Multiple new therapeutic options for almost all subsets of breast cancer have emerged in the past 2 years. Most importantly, for hormone-receptor-positive breast cancer, addition of abemaciclib to endocrine therapy in the adjuvant setting and alpelisib for PIK3CA-mutant refractory advanced disease have been shown to improve the survival outcomes. Addition of pembrolizumab or atezolizumab to neoadjuvant chemotherapy has significantly increased the pathological complete response rate for early triple-negative breast cancer, while adjuvant metronomic capecitabine for 1 year has led to improved disease-free survival. Moreover, adjuvant adotrastuzumab emtansine fared better than trastuzumab in the management of residual disease after neoadjuvant treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, while tucatinib and neratinib have shown meaningfully improved progression-free survival in HER2-positive advanced disease, including patients with cranial nervous system involvement. Expanding access to these advances is soon expected to transform the way we treat breast cancers.

Indirect comparison between immunotherapy alone and immunotherapy plus chemotherapy as first-line treatment for advanced non-small cell lung cancer: a systematic review

ObjectivesUse of immune checkpoint inhibitors as first-line treatment for advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) remains controversial. Clinical trials comparing single-drug immunotherapy (IO) with immunotherapy plus chemotherapy (IC)...

Involvement of radiologists in oncologic multidisciplinary team meetings: an international survey by the European Society of Oncologic Imaging

ObjectivesMultidisciplinary tumour boards (MTBs) play an increasingly important role in managing cancer patients from diagnosis to treatment. However, many problems arise around the organisation of MTBs, both in terms of organisation-administration and time management. In this context, the European Society of Oncologic Imaging (ESOI) conducted a survey among its members, aimed at assessing the quality and amount of involvement of radiologists in MTBs, their role in it and related issues.MethodsAll members were invited to fill in a questionnaire consisting of 15 questions with both open and multiple-choice answers. Simple descriptive analyses and graphs were performed.ResultsA total of 292 ESOI members in full standing for the year 2018 joined the survey. Most respondents (89%) declared to attend MT-Bs, but only 114 respondents (43.9%) review over 70% of exams prior to MTB meetings, mainly due to lack of time due to a busy schedule for imaging and reporting (46.6%). Perceived benefits (i.e. surgical and histological feedback (86.9%), improved knowledge of cancer treatment (82.7%) and better interaction between radiologists and referring clinicians for discussing rare cases (56.9%)) and issues (i.e. attending MTB meetings during regular working hours (71.9%) and lack of accreditation with continuing medical education (CME) (85%)) are reported.ConclusionsDespite the value and benefits of radiologists’ participation in MTBs, issues like improper preparation due to a busy schedule and no counterpart in CME accreditation require efforts to improve the role of radiologists for a better patient care.Key Points• Most radiologists attend multidisciplinary tumour boards, but less than half of them review images in advance, mostly due to time constraints.• Feedback about radiological diagnoses, improved knowledge of cancer treatment and interaction with referring clinicians are perceived as major benefits.• Concerns were expressed about scheduling multidisciplinary tumour boards during regular working hours and lack of accreditation with continuing medical education.

Unconscious Bias in Speaker Introductions at a Surgical Oncology Meeting: Hierarchy Reigns Over Gender.

Recent reviews of medical conferences have shown that women were less likely to receive a formal introduction compared with men. We examined speaker introductions at the Society of Surgical Oncology (SSO) annual meeting to determine whether similar biases exist within our organization. An observational study of video-archived speaker introductions at the 2018 and 2019 SSO annual meetings was conducted. Professional address was defined as professional title followed by full name or last name. Multivariable logistic regression was used to identify factors associated with form of address. There were 499 speaker introductions reviewed. Speakers included 290 (58%) men and 238 (49%) post-graduate trainees (residents and fellows). A non-professional form of address was used to introduce 148 (30%) speakers and was most often used for post-graduate trainees (33%). Full professors were more likely than junior faculty to introduce speakers with a non-professional form of address (37% of full professors vs 18% of assistant professors, p < 0.001). In multivariable regression analysis these findings persisted. Trainees were 2.8 times more likely to receive a non-professional form of address (p = 0.003). Use of a non-professional introduction did not significantly vary by the speaker's nor the introducer's gender. Residents and fellows were more likely to receive a non-professional form of address, and the likelihood of this increased with rising seniority of the introducer. The manner of speaker introduction did not vary by gender in our organization. More research is needed to explore the influence of these disparities on academic advancement for the next generation of surgical oncologists.