Impact of treatment line on outcomes with salvage ipilimumab + nivolumab in metastatic renal cell carcinoma (mRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17092-e17092
Author(s):  
Ritesh Kotecha ◽  
Chung-Han Lee ◽  
Andrea Knezevic ◽  
Neil J. Shah ◽  
Maria Isabel Carlo ◽  
...  
Keyword(s):  
Treatment Options ◽  
Immune Checkpoint Blockade ◽  
Clinical Progression ◽  
Start Time ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Time To Treatment Failure ◽  
Treatment Sequencing ◽  
Line Setting

e17092 Background: With the approval of ipilimumab plus nivolumab (I+N) and other immune checkpoint blockade (ICB) based combinations in the first-line setting, the role of I+N for salvage is of high interest for treatment sequencing, yet data is limited. Methods: We conducted a retrospective review of mRCC patients (pts) treated with I+N in the second-line (2L) and beyond settings at MSKCC between 2013-2019. Pt demographics, treatment history and toxicity were compiled. IMDC-risk status was calculated at I+N therapy start. Time to treatment failure (TTF) was defined as earliest date of clinical progression, therapy change or death, and overall survival (OS) was estimated by Kaplan-Meier method. Results: 36 pts received I+N in the 2+L setting, including 31/36 with clear-cell histology. Evaluable IMDC-risk at I+N start was favorable in 1/35 and intermediate-poor in 34/35 pts. The most common 1L therapies were anti-VEGF (22/36) and VEGF + ICB (6/36). 11/36 pts had ICB treatment exposure prior to I+N therapy. I+N therapy in the 2L, 3L and 4L was in 21/36, 8/36 and 7/36 pts, respectively, and 7/36 pts continue I+N at data cut-off. 8/36 pts discontinued I+N due to toxicity, 20/36 pts discontinued therapy due to disease progression, and 1 pt discontinued per pt preference. Cohort median OS was 14.8 months (95%CI: 4.2-44). Overall median TTF was 5.0 months (95%CI: 2.9-14.4), and TTF per 2L, 3L and 4+L was 8.3, 8.9 and 2.5 months, respectively. The number of patients who completed all 4 I+N induction cycles in the 2L, 3L, and 4+L was 11/21 (52%), 5/8 (63%), and 1/7 (14%). The number of patients who subsequently received nivolumab maintenance therapy after induction was 16/21 (76%) in the 2L, 1/8 (13%) in the 3L, and 0/7 (0%) in 4+L. Conclusions: With emerging treatment options for mRCC, this study reveals activity and safety for I+N in 2+L settings. In this limited cohort, completion of induction ipilimumab and use of maintenance nivolumab decline in later-line settings, suggesting limitations as salvage therapy. [Table: see text]

scholarly journals Emerging Role of Immune Therapy in HCC

2021 ◽  
Author(s):  
Stacey M. Stein
Keyword(s):  
Kinase Inhibitors ◽  
Immune Therapy ◽  
Treatment Options ◽  
Single Agent ◽  
Small Subset ◽  
Vascular Endothelial ◽  
Number Of Patients ◽  
Endothelial Growth Factor ◽  
Expected Increase

AbstractHepatocellular carcinoma (HCC) remains a prevalent cancer diagnosis with an expected increase in incidence in the next decade. Treatment options for advanced disease have expanded significantly in the last decade since sorafenib was first approved in 2007. There have been approvals for multiple tyrosine kinase inhibitors (TKIs) with modest improvements in survival. Single-agent PD-1 inhibition has shown responses in ∼15% of patients, with a tail of the curve that is very beneficial to a small subset of patients. Most recently, studies of combination therapy with immune therapy drugs are showing more durable responses in a larger number of patients with unprecedented response rates over 30%. Different strategies have been pursued, including PD-1 and PD-L1 combinations with vascular endothelial growth factor inhibition, TKIs, and anti-CTLA-4 antibodies. This article provides a review of studies both completed and ongoing with immune therapy in advanced HCC.

scholarly journals The use of multi-omics data and approaches in breast cancer immunotherapy: a review

2020 ◽  
Vol 16 (27) ◽  
pp. 2101-2119
Author(s):  
Ka Lun Leung ◽  
Devika Verma ◽  
Younus Jamal Azam ◽  
Emyr Bakker
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Clinical Trial Design ◽  
Immune Checkpoint Blockade ◽  
Omics Data ◽  
Treatment Side Effects ◽  
The Usa ◽  
Type Data ◽  
Target Cancer

Breast cancer is projected to be the most common cancer in women in 2020 in the USA. Despite high remission rates treatment side effects remain an issue, hence the interest in novel approaches such as immunotherapies which aim to utilize patients’ immune systems to target cancer cells. This review summarizes the basics of breast cancer including staging and treatment options, followed by a discussion on immunotherapy, including immune checkpoint blockade. After this, examples of the role of omics-type data and computational biology/bioinformatics in breast cancer are explored. Ultimately, there are several promising areas to investigate such as the prediction of neoantigens and the use of multi-omics data to direct research, with noted appropriate in clinical trial design in terms of end points.

scholarly journals Response to anti-PD1 immunotherapy in patients with metastatic cutaneous sarcoma: case reports and literature review

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Aline Cristini Vieira ◽  
Thais Baccili Cury Megid ◽  
Raissa Melo ◽  
David Muniz ◽  
Alessandra Corte Real Salgues ◽  
...  
Keyword(s):  
Case Reports ◽  
Treatment Options ◽  
Surgical Excision ◽  
Predictive Biomarker ◽  
Immune Checkpoint Blockade ◽  
Targeted Agents ◽  
Mutational Burden ◽  
Metastatic Setting ◽  
Tumor Mutational Burden

Abstract Dermal sarcomas represent a group or rare malignancies of mesenchymal origin. Although surgical excision with wide margins can be curative, in the advanced/metastatic setting, treatment options are limited and the benefit from anthracycline-based chemotherapy or targeted agents is usually short-lived. Tumor mutational burden and PD-L1 expression scores can be used as predictive biomarker for response to immunotherapy in some metastatic cancers. The role of immune-checkpoint blockade for sarcoma patients remains investigational. Here we present three cases of dermal sarcomas with high TMB and PD-L1 expression and responses to anti-PD1 agents in two of them.

Is proliferative index (Ki-67) useful to stratify patients (pts) with G2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs)? Clinicopathologic correlation.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 255-255
Author(s):  
Martin Angel ◽  
Juan O Connor ◽  
Veronica Pesce ◽  
Guillermo Ariel Mendez ◽  
Claudia Bestani ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Roc Curve ◽  
Target Therapy ◽  
Treatment Options ◽  
Rank Test ◽  
Roc Curve Analysis ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Kaplan Meier

255 Background: Grade 2 (G2) Neuroendocrine tumors (NETs), of the digestive tract is a heterogeneous group of tumors. Several treatment options including chemotherapy and target therapy are available, but there is a lack of prospective trials assessing the role of pronostic factors in this population. Aim(s): to analyze prognostic factors and clinical characteristics in a population of patients with G2 GEP-NETs. To determine the role of ki 67 in the stratification of G2 population. Methods: Study population was obtained from our prospective database (Argentum Group). Survival was estimated using the Kaplan-Meier method and compared between Ki-67 quartiles using the log-rank test. Value of Ki-67 to discriminate mortality was assesed with a ROC curve analysis Results: 144 pts were evaluated. Mean age 54.9, 46.7% male. 102 (70.8%) with metastatic disease, mainly hepatic in 97 pts. (67.4%). 67.9 % underwent surgery. 34% received chemotherapy, and 10.9% target therapy. Median Ki-67 value was 6 (IQR 4-10), ROC curve=0.62 (95% CI 0.53 a 0.72 p=0.021. cut-off: 6.5 (sensitivity 62.2%, specificity 57.7%). Median survival was 97, 67, 51 and 27 months according stratification by quartile (p.001), 45 events (31.7%). Conclusions: Our results suggest that in the heterogenous G2 GEP-NETs there are significant differences in survival. This study was underpowered to detect differences between Ki-67 quartiles, we detected that chemotherapy was mostly used in the higher quartiles.

Second-line (SL) chemotherapy containing oxaliplatin (OXA) in metastatic pancreatic cancer (PC): Whom should we trust?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15719-e15719
Author(s):  
Chiara Caparello ◽  
Caterina Vivaldi ◽  
Francesco Montagnani ◽  
Gianna Musettini ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Random Effect ◽  
Significant Heterogeneity ◽  
First Line ◽  
Hazard Ratios ◽  
Randomized Phase Ii ◽  
Number Of Patients ◽  
Personalized Approach ◽  
Line Setting

e15719 Background: After the intensification of first-line treatment in metastatic PC the number of patients fit and able to receive a SL treatment is increasing; despite these results, the choice of SL chemotherapy remains a challenging issue. The role of OXA in SL setting has given conflicting results in CONKO-003 and PANCREOX trials; the reasons of this inconsistency are difficult to understand. Methods: In order to detect a possible advantage from the use of oxaliplatin in SL, we pooled together the results of randomized phase II/III studies adding OXA to fluoropyrimidines after a gemcitabine-based first-line. Hazard ratios (HRs) for progression-free (PFS) and overall survival (OS) with 95% confidence intervals (CIs) were extracted, while the number of events was used for RR to determine odds ratio (OR) with corresponding 95%CIs. Fixed-effect and random-effect models were used as appropriate, on the basis of the evidence of a non-significant or significant heterogeneity among trials, respectively. The Review Manager software was used (version 5.3). Results: Three studies were identified; main characteristics and results are summarized in the table. No benefit in overall survival derived from the use of OXA (HR 1.03, 95% CI, 0.64-1.67; p=0.90) but significant heterogeneity was reported (p=0.003); the addition of OXA produced a significant benefit in terms of PFS (HR 0.81, 95% CI 0.68-0.97; p=0.02) with a higher chance of response (OR 1.81, 95% CI 1.01-3.24; P=0.05). Interestingly heterogeneity between trials was less evident in PFS and RR than in OS suggesting that this could be a confounding element in the interpretation of data. Conclusions: The reasons of conflicting results concerning the use of oxaliplatin doublets in SL setting are not clear. Given the recent advances in first-line setting, it would be interesting to identify an optimal sequential strategy, hopefully in a personalized approach. [Table: see text]

Nanotechnology-based platforms to improve immune checkpoint blockade efficacy in cancer therapy

2020 ◽  
Author(s):  
Deeksha G Lahori ◽  
Pegah Varamini
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Standard Of Care Treatment ◽  
Anticancer Treatment ◽  
Novel Strategy

In recent years, cancer immunotherapy has evolved as an exciting novel strategy for researchers and clinicians worldwide. Immunotherapeutic agents such as immune checkpoint blockers have changed the standard-of-care treatment provided for many tumors. Unfortunately, only a small proportion of patients respond effectively to these checkpoint inhibitors. Moreover, the immunosuppressive pathways for cancer are probably too complicated to achieve optimal outcome with immune checkpoint inhibitors alone. Combining current therapeutic options and immunotherapy-based approaches is being explored as an effective strategy to treat cancer. The use of nanotechnology-based platforms for delivery of immunotherapeutic agents or combination therapy could offer a major advantage over conventional anticancer treatment options. This review highlights the potential role of different nanotechnology-based strategies in improving the efficacy of immune checkpoint blockade therapy.

scholarly journals The Way to a Human’s Brain Goes Through Their Stomach: Dietary Factors in Major Depressive Disorder

2020 ◽  
Vol 14 ◽  
Author(s):  
Janine Aly ◽  
Olivia Engmann
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Treatment Options ◽  
Dietary Factors ◽  
Omega 3 ◽  
Major Depressive ◽  
Number Of Patients ◽  
Omega 6 ◽  
And Behavior

Globally, more than 250 million people are affected by depression (major depressive disorder; MDD), a serious and debilitating mental disorder. Currently available treatment options can have substantial side effects and take weeks to be fully effective. Therefore, it is important to find safe alternatives, which act more rapidly and in a larger number of patients. While much research on MDD focuses on chronic stress as a main risk factor, we here make a point of exploring dietary factors as a somewhat overlooked, yet highly promising approach towards novel antidepressant pathways. Deficiencies in various groups of nutrients often occur in patients with mental disorders. These include vitamins, especially members of the B-complex (B6, B9, B12). Moreover, an imbalance of fatty acids, such as omega-3 and omega-6, or an insufficient supply with minerals, including magnesium and zinc, are related to MDD. While some of them are relevant for the synthesis of monoamines, others play a crucial role in inflammation, neuroprotection and the synthesis of growth factors. Evidence suggests that when deficiencies return to normal, changes in mood and behavior can be, at least in some cases, achieved. Furthermore, supplementation with dietary factors (so called “nutraceuticals”) may improve MDD symptoms even in the absence of a deficiency. Non-vital dietary factors may affect MDD symptoms as well. For instance, the most commonly consumed psychostimulant caffeine may improve behavioral and molecular markers of MDD. The molecular structure of most dietary factors is well known. Hence, dietary factors may provide important molecular tools to study and potentially help treat MDD symptoms. Within this review, we will discuss the role of dietary factors in MDD risk and symptomology, and critically discuss how they might serve as auxiliary treatments or preventative options for MDD.

scholarly journals Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19

2020 ◽  
Vol 120 (12) ◽  
pp. 1629-1641
Author(s):  
Selin Gencer ◽  
Michael Lacy ◽  
Dorothee Atzler ◽  
Emiel P. C. van der Vorst ◽  
Yvonne Döring ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Viral Entry ◽  
Treatment Options ◽  
Microvascular Dysfunction ◽  
Organ Systems ◽  
Number Of Patients ◽  
History Of ◽  
Potential Impact ◽  
Shed Light

AbstractThe global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin–angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

scholarly journals Nasopharyngeal mucoepidermoid carcinoma: a case report and review of its current management

2021 ◽  
Vol 7 (11) ◽  
pp. 1821
Author(s):  
Purushotman Ramasamy ◽  
Vigneswaran Kumarasamy ◽  
Pathma Letchumanan ◽  
Harvinder Singh Dalip Singh
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Treatment Options ◽  
Endoscopic Endonasal ◽  
Salivary Gland Tumours ◽  
Sinonasal Malignancies ◽  
Number Of Patients ◽  
Sporadic Cases ◽  
The Right ◽  
Selection Of

<p class="abstract">Salivary gland tumours arising at the nasopharynx is highly infrequent. Among them the commonest is mucoepidermoid carcinoma (MEC). Reports with a larger number of patients are often from Asian countries where nasopharyngeal squamous cell carcinoma is also predominant. Although nasopharyngeal MEC (NMEC) is a disease of adults, sporadic cases amongst children have been reported. We report a case of a 32 years old man presented with complaining of intermittent epistaxis over a year. His nasal endoscopy showed friable polypoid tumour at the right choanae. Histopathology revealed a NMEC and he underwent endoscopic endonasal nasopharyngectomy with adjuvant radiotherapy. The optimal treatment for NMEC is arbitrary due to the lack of evidence. However, unlike most sinonasal malignancies, NMEC has the tendency to manifest itself early and has good response to the treatment. Therefore, in this article we describe the clinical features and justifications for the selection of treatment options including surgical and non-surgical therapies and including the role of neck dissection.</p>

Phosphorylated Akt and MAPK expression in primary tumors and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14086-e14086
Author(s):  
Riccardo Giampieri ◽  
Mario Scartozzi ◽  
Elena Maccaroni ◽  
Alessandra Mandolesi ◽  
Simona Biagetti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Phosphorylated Akt ◽  
Line Setting ◽  
Colorectal Cancer Patients

e14086 Background: Other than the well-known EGFR pathway activation via the Ras-Raf-MAP-kinase, a possible role of other potential biomarkers could be relevant in determining resistance to anti-EGFR treatment, such as the protein-serine/threonine kinase Akt. We tried to assess the role of Akt and MAPK expression in metastatic colorectal cancer patients and their relationship with outcome for patients receiving Irinotecan-Cetuximab. Methods: Eligible patients were metastatic colorectal cancer patients treated in 2nd or 3rd line setting with a irinotecan-cetuximab based regimen. Patients were tested for K-ras status and subsequently assessed by immunoistochemistry for pAkt and MAPK expression, both in primary tumours and metastases whenever sufficient tissue was available. The role of pAkt and MAPK expression was evaluated for K-ras wild type patients for different likelihood of response, overall survival and progression free survival. Response was evaluated by RECIST criteria. Survival analysis was performed via Kaplan-Meier method. Results: In metastases pAkt correlated with RR (9% vs. 58%, p=0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs, 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p=0.0004). At multivariate analysis pAkt and pMAPK in metastases were able to independently predict PFS. pAkt in metastases independently correlated with RR as well. Conclusions: pAkt and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAkt and pMAPK metastases expression targeting these factors may be crucial.

Sign in / Sign up

Export Citation Format

Share Document