Reassessing the Role of Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma in 2019

2019 ◽  
pp. 276-283 ◽  
Author(s):  
Sarah P. Psutka ◽  
Steven L. Chang ◽  
David Cahn ◽  
Robert G. Uzzo ◽  
Bradley A. McGregor
Keyword(s):  
Multimodal Therapy ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Therapeutic Approaches ◽  
Cytoreductive Nephrectomy ◽  
Free Survival ◽  
Surgical Interventions ◽  
Prospective Trials

Cytoreductive nephrectomy (CRN) has long been considered a standard of care in the management of mRCC. This is largely based on randomized trials in the era of interferon (IFN) that demonstrate an improvement in overall survival (OS). With the advent of targeted therapies, the role of CRN has been questioned and multiple retrospective analyses have shown a potential benefit, particularly in intermediate-risk disease. Two long-awaited prospective trials have been published in the past year that explore the role of CRN. The CARMENA trial randomly assigned patients to therapy with sunitinib with or without CRN, showing noninferiority of sunitinib alone versus sunitinib plus CRN with a median OS of 18.4 months versus 13.9 months, respectively (hazard ratio [HR] for mortality, 0.89; 95% CI, 0.71–1.1). The SURTIME trial randomly assigned patients to immediate CRN followed by sunitinib versus a deferred CRN after three cycles of sunitinib. Analysis is limited by early termination as a result of low accrual. Although there was no difference in progression-free survival (PFS), median OS was significantly improved among patients in the deferred CRN arm (HR, 0.57; 95% CI, 0.34–0.95; p = .032). Early systemic therapy is paramount, but there are patients who may derive benefit by incorporating the removal of the primary tumor in their multimodal therapy, perhaps in a deferred setting. As systemic treatment paradigms shift and immunotherapy again moves to the frontline setting with the potential for novel therapeutic approaches, the role of CRN will continue to evolve with the potential to offer surgical interventions with minimal, if any, delay in systemic treatment.

Systematic literature review of clinical outcomes in adults with metastatic or advanced synovial sarcoma

2020 ◽  
Vol 16 (35) ◽  
pp. 2997-3013
Author(s):  
Kentaro Kogushi ◽  
Michael LoPresti ◽  
Shunya Ikeda
Keyword(s):  
Synovial Sarcoma ◽  
High Frequency ◽  
Clinical Evidence ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Treatment Modalities ◽  
Free Survival ◽  
New Treatment ◽  
Poor Outcomes

Background: Synovial sarcoma (SS) is a rare, aggressive soft tissue sarcoma with a poor prognosis after metastasis. The objective of this study was to conduct a systematic review of the clinical evidence for therapeutic options for adults with metastatic or advanced SS. Materials & methods: Relevant databases were searched with predefined keywords. Results: Thirty-nine publications reported clinical data for systemic treatment and other interventions. Data on survival outcomes varied but were generally poor (progression-free survival: 1.0–7.7 months; overall survival: 6.7–29.2 months) for adults with metastatic and advanced SS. A high frequency of neutropenia with systemic treatment and low quality of life post-progression were reported. Conclusion: Reported evidence suggests poor outcomes in adults with metastatic and advanced SS and the need for the development of new treatment modalities.

scholarly journals Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 324
Author(s):  
Jacob P. Fisher ◽  
David C. Adamson
Keyword(s):  
Controlled Trial ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Significant Survival ◽  
One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

scholarly journals PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

2021 ◽  
Author(s):  
Jonathan Weller ◽  
Sophie Katzendobler ◽  
Philipp Karschnia ◽  
Stefanie Lietke ◽  
Rupert Egensperger ◽  
...  
Keyword(s):  
Stereotactic Biopsy ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
First Relapse ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
Histological Progression

Abstract Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

scholarly journals Durable Response to Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, and Prednisone (BV-CHP) in a Patient with CD30-Positive PTCL Arising as a Post-Transplant Lymphoproliferative Disorder (PTLD)

2021 ◽  
Vol 28 (6) ◽  
pp. 5067-5072
Author(s):  
Jennifer Hong ◽  
William T. Johnson ◽  
Saritha Kartan ◽  
Anitha S. Gonsalves ◽  
Jonathan M. Fenkel ◽  
...  
Keyword(s):  
T Cell ◽  
Poor Prognosis ◽  
Lymphoproliferative Disorder ◽  
Progression Free Survival ◽  
Brentuximab Vedotin ◽  
Added Value ◽  
Front Line ◽  
Durable Response ◽  
Free Survival ◽  
Prospective Trials

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. Herein we report a case of CD30-positive T-cell PTLD that was successfully treated with BV-CHP, suggesting the added value of the addition of BV to chemotherapy, contributing to our patient’s long and ongoing progression-free survival. To our knowledge, this is the first documented case of successful treatment using BV-CHP for a CD30-positive, EBV-negative, late T-cell PTLD.

scholarly journals Combined BRAF and MEK Inhibition with Vemurafenib and Cobimetinib for Patients with Advanced Melanoma

2017 ◽  
Vol 13 (01) ◽  
pp. 1
Author(s):  
Antonio M Grimaldi ◽  
Ester Simeone ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Paolo A Ascierto ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Combined Therapy ◽  
Acquired Resistance ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Mek Inhibition ◽  
Braf Mutant

Acquired resistance is the most common cause of BRAF inhibitor monotherapy treatment failure, with the majority of patients experiencing disease progression with a median progression-free survival of 6-8 months. As such, there has been considerable focus on combined therapy with dual BRAF and MEK inhibition as a means to improve outcomes compared with monotherapy. In the COMBI-d and COMBI-v trials, combined dabrafenib and trametinib was associated with significant improvements in outcomes compared with dabrafenib or vemurafenib monotherapy, in patients with BRAF-mutant metastatic melanoma. The combination of vemurafenib and cobimetinib has also been investigated. In the phase III CoBRIM study in patients with unresectable stage III-IV BRAF-mutant melanoma, treatment with vemurafenib and cobimetinib resulted in significantly longer progression-free survival and overall survival (OS) compared with vemurafenib alone. One-year OS was 74.5% in the vemurafenib and cobimetinib group and 63.8% in the vemurafenib group, while 2-year OS rates were 48.3% and 38.0%, respectively. The combination was also well tolerated, with a lower incidence of cutaneous squamous-cell carcinoma and keratoacanthoma compared with monotherapy. Dual inhibition of both MEK and BRAF appears to provide a more potent and durable anti-tumour effect than BRAF monotherapy, helping to prevent acquired resistance as well as decreasing adverse events related to BRAF inhibitor-induced activation of the MAPK-pathway. Combined BRAF and MEK inhibition is the standard of care in patients with advanced BRAF-mutant melanoma.

scholarly journals High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun-Qian Cui ◽  
Fei Meng ◽  
Wen-Li Zhan ◽  
Zhou-Tong Dai ◽  
Xinghua Liao
Keyword(s):  
Potential Role ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
High Expression ◽  
Poor Survival ◽  
Free Survival

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.

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