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Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC. [ABSTRACT FROM AUTHOR]

Purpose: Xevinapant is an orally available inhibitor of apoptosis proteins (IAP) inhibitor. Preclinical data suggest that IAP antagonism may synergize with immune checkpoint blockers by modulating the NFκB pathway in immune cells., Patients and Methods: Adult patients with non-high microsatellite instability advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer were enrolled in this phase Ib/II study and received pembrolizumab 200 mg every 3 weeks intravenously, and ascending doses of oral xevinapant (100, 150, and 200 mg daily for 14 days on/7 days off). Dose escalation followed a 3+3 design with a 21-day dose-limiting toxicity (DLT) evaluation period. Following the determination of the recommended phase II dose (RP2D), 14 patients with PDAC and 14 patients with colorectal cancer were enrolled in expansion cohorts to assess preliminary efficacy., Results: Forty-one patients (26 males) with a median age of 64 years were enrolled: 13 in the dose escalation and 28 in the two expansion cohorts. No DLT was observed during dose escalation. The RP2D was identified as xevinapant 200 mg/day + pembrolizumab 200 mg every 3 weeks. The most common adverse events (AE) were fatigue (37%), gastrointestinal AE (decreased appetite in 37%, nausea in 24%, stomatitis in 12%, and diarrhea and vomiting in 10% each), and cutaneous AE (pruritus, dry skin, and rash seen in 20%, 15%, and 15% of patients, respectively). The best overall response according to RECIST1.1 was partial response (confirmed) in 1 (3%), stable disease in 4 (10%), and progressive disease in 35 (88%)., Conclusions: Xevinapant combined with pembrolizumab was well tolerated with no unexpected AEs. However, antitumor activity was low., (©2024 American Association for Cancer Research.)

Bispecific therapies targeting CD3, so-called T-cell engagers (TCE), belong to the new spectrum of anti-tumor immunotherapies stimulating T-lymphocytes. TCE are unique constructs targeting the MHC-independent CD3 epsilon subunit (CD3e) and a tumor antigen. To date, only blinatumomab have reached market agreements in lymphoid malignancies with constructs targeting CD3exCD19. Other TCE are in advances development, with promising results targeting CD20 and BSMA in lymphoma and myeloma. These successes have relaunched the development of TCE in solid tumors, bringing mixed results so far (notably in terms of tolerance). Still, TCE pave the way to new immunotherapy in tumors considered to be refractory to inhibitors of immune checkpoints such as prostate cancer or colorectal cancer., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Seminomatous (SGCT) and non-seminomatous (NSGCT) germ cell tumors (GCT) are rare but their incidence are increasing. We will discuss different therapeutic strategies in relapse disease: patients with stage I germ cell tumor have an excellent prognosis with a cure rate approaching 98-99 %, whatever the histology and the chosen treatment (surveillance strategy or adjuvant treatment). Relapses are observed among 20% of patients with stage I SGCT or low risk NSGCT and 50 % of patients with high risk NSGCT. Patients are treated according to the international prognosis group (IGCCCG) for SGCT and low risk NSGCT, naïve of chemotherapy. After an adjuvant treatment, the protocol must be adapted to the number of previous cycles (1 or 2 BEP) and to the prognosis group. Five to 50% of patients relapse after a first line of metastatic chemotherapy according to initial prognosis group. Dose-dense chemotherapy according to the GETUG13 protocol reduces the risk of relapse for the patients with poor-risk group NSGCT and unfavorable tumor marker decline. The prognosis of patients with relapsed or refractory GCT after a first line is more negative since only half of them will be cured by salvage standard chemotherapy. An international therapeutic trial (TIGER) is ongoing in first line salvage treatment evaluating high-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (HSCT). Finally, developing biomarkers for predicting clinical relapse, the management in expert centers of these patients and participation in therapeutic innovation are important perspectives for a better understanding and treatment of these patients with a poorer prognosis., (Copyright © 2020. Published by Elsevier Masson SAS.)

More than 80 % of patient with metastatic germ cell tumor are cured with first line chemotherapy. Twenty to 30 % of patients will experience relapse or refractory disease with a very poor long-term prognosis. Most of them had metastatic germ cell tumors with a poor prognosis according to the international germ cell classification collaborative group (IGCCCG). The role of treatment intensification by high dose chemotherapy (HDCT) followed by stem cell rescue has not been demonstrated yet in the first line setting compared to standard chemotherapy. The role of HDCT in first or second salvage is also not yet demonstrated, many studies have been published in this situation with a lot of different regimen. Outside clinical trial, HDCT remains an option in salvage therapy, depending on many factors including prognostics factors, previous therapy, general condition and reference center consideration to select eligible patient who could benefit the most of this approach. Results from the international randomized trial TIGER will provide evidence-based information for HDCT strategy., (Copyright © 2020 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)