Pembrolizumab Articles

In November 2016, the results of a phase III clinical trial with the protein cell death (PD)-1 inhibitor pembrolizumab for second-line treatment of metastatic urothelial carcinoma were published and showed an overall survival benefit in comparison with conventional chemotherapy with vinflunine, docetaxel, or paclitaxel.

The first-line therapy of metastatic bladder cancer (urothelial carcinoma, UC) depends on whether a patient is cisplatin-fit or not. Cisplatin-fit patients should be treated with the standard chemotherapy protocol GC (gemcitabine/cisplatin) or alternatively MVAC (methotrexate/vinblastine/doxorubicin/cisplatin).

Prostate cancer (PCA) seems to be more of an immunologic desert than other tumor entities. It is striking that only rarely does prostate cancer show abundant immune cells and a proimmunogenic microenvironment.

To determine which of the approved immune checkpoint inhibitors is the optimal treatment in metastatic urothelial bladder cancer.

Only the pivotal Phase III trials of second-line metastatic urothelial bladder cancer were included in this network meta-analysis.

Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.

Renal cell carcinoma is a common malignancy of the genitourinary system and is the eight most common cancer type in the United States. The overall incidence of renal cell carcinoma appears to be increasing but death rates have been declining.

Urothelial carcinoma (UC) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable.

Immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are the most commonly used medications in metastatic renal cell carcinoma (mRCC). Recently, large clinical trials have shown favorable outcomes in patients treated with combined immune checkpoint plus VEGFR inhibition compared with VEGFR inhibition alone.

Urothelial carcinoma (UC) is the most common subtype of bladder cancer. The randomized phase 3 KEYNOTE-045 trial showed that pembrolizumab, used as second-line therapy significantly prolonged overall survival with fewer treatment-related adverse events than chemotherapy for advanced UC.

PD-1 checkpoint inhibitors are associated with a specific spectrum of immune-related adverse events. This spectrum is different from toxicities known for kinase inhibitors or cytotoxic drugs. Since PD-1 directed therapies show effectivity in an increasing number of malignant diseases, their clinical usage will increase rapidly.

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.

An 83-year-old man received pembrolizumab treatment after anticancer chemotherapy with gemcitabine and cisplatin for advanced bladder cancer. Pathological findings revealed invasive urothelial carcinoma with squamous differentiation before treatment.

Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited.

The U.S. Food and Drug Administration (FDA) granted accelerated approval to atezolizumab and pembrolizumab in April and May 2017, respectively, for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.

No head-to-head clinical trials compare contemporary first-line therapies for metastatic renal cell carcinoma (mRCC). A network meta-analysis provides an approach for quantitative analysis.

To indirectly compare the efficacy and safety of first-line treatments for mRCC in the intention-to-treat (ITT) population and by clinical risk group.

A number of PD-1/PD-L1 inhibitors have recently been approved for use in patients with locally advanced or metastatic urothelial carcinoma (UC) on the basis of results from several clinical trials.

To review the evidence from these trials and consider what it means for the use of these drugs in first-line and post-platinum settings in real-life clinical practice.

Germline genetic testing increasingly identifies advanced prostate cancer (PCa) patients who are candidates for precision therapies. The Prostate Cancer Clinical Trials Consortium (PCCTC) established the Germline Genetics Working Group to provide guidance and resources to expand effective use of germline genetic testing.

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).

Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity.

Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents.

Immunotherapy is rapidly transforming cancer care across a range of tumor types. Although Sipuleucel-T represented the first successful vaccine for the treatment of established cancer, other immunotherapeutic approaches for prostate cancer such as checkpoint inhibitors have been relatively disappointing to date.

The PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC).

To evaluate the ability of molecular signatures to predict the pathological complete response (CR: ypT0N0) and progression-free survival (PFS) after pembrolizumab and RC.

Recent meta-analyses on checkpoint inhibitors in cancer report conflicting data regarding the association of patient gender with inhibitor efficacy. In advanced kidney cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared with standard of care, but the role of patient gender on treatment outcome is unclear.

Background: Nonmuscle-invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with high rates of disease recurrence and progression. Current treatment for high-risk NMIBC involves Bacillus Calmette-Guérin (BCG) therapy, but treatment options are limited for patients with recurrent or BCG-unresponsive disease.

Lenvatinib plus everolimus is approved for the treatment of advanced renal cell carcinoma (RCC) after one prior vascular endothelial growth factor-targeted therapy. Lenvatinib plus pembrolizumab demonstrated promising antitumor activity in a Phase I/II trial of RCC.

Brain metastasis is a common complication of advanced malignancies, especially, lung cancer, breast cancer, renal cell carcinoma, and melanoma. Traditionally surgery, when indicated, and radiation therapy, either as whole-brain radiation therapy or stereotactic radiosurgery, constituted the major treatment options for brain metastases.

Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer.

In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients.

The advent of immunotherapy has heralded a number of significant advances in the treatment of particular malignancies associated with poor prognosis (melanoma, non-small-cell lung, renal and head/neck cancers).

Oncologic immunotherapies use a patient's immune response to eliminate tumor cells by modulation of immune checkpoints, including programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) proteins.

Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1).

Testicular germ cell tumor (GCT) is the most common malignancy in young males between the ages of 15 to 35 years. Although the overall cure rate of GCTs approaches 95%, almost 25% of patients with distant metastases die from the cancer.

Renal cell carcinoma (RCC) is among the 10 most common cancers in the USA. One-third of the patients diagnosed with this cancer present with locally advanced or metastatic disease. In the past, advanced disease conferred poor survival outcomes; however, the treatment paradigm for RCC has been revolutionized twice since 2005.

To characterize the outcomes of patients with nonmelanoma solid tumors receiving anti-PD-1 immunotherapy not funded by the Australian Pharmaceutical Benefits Scheme.

Medical records of patients with metastatic nonmelanoma tumor diagnoses treated with anti-PD-1 (self-funded pembrolizumab or nivolumab through an access program) from January 1, 2014, to December 31, 2016, at Peter MacCallum Cancer Centre, were retrospectively reviewed.

Until recently, systemic chemotherapy was the only option for treating bladder cancer and outcomes remained dismal. After a long gap of no progress for 40 years, immuno-therapy with checkpoint inhibitors (PDL1 and PD1) has revolutionized the treatment paradigm of bladder cancer, with five approved agents to treat platinum-refractory bladder cancer since the first approval of atezolizumab in May 2016.

Until recently, patients with locally advanced or metastatic urothelial carcinoma after progression on cisplatin-containing chemotherapy had limited systemic treatment options with no significant survival benefit and poor tolerability.

Pembrolizumab is an immune checkpoint inhibitor (ICI) that targets the programmed cell death (PD)-1 receptor. It significantly increases the overall survival in patients with locally advanced or metastatic urothelial cancer.

The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine).

Tumor lysis syndrome is uncommon in solid tumors but with the use of immunotherapy (checkpoint inhibitors) their incidence is increasing. Physicians need to take adequate precautions while treating patients with immunotherapy.

Ipilimumab, pembrolizumab, and nivolumab are checkpoint inhibitors (CPI) that activate T cell-mediated immune response. CPI can provide durable benefits to some cancer patients with melanoma, renal cell cancer, non-small cell lung cancer, and a growing list of other cancers.

Pembrolizumab is a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1) found on T and pro-B cells. Pembrolizumab prevents PD-1 ligation by both PD-L1 and PD-L2, preventing the immune dysregulation that otherwise occurs when T-cells encounter cells expressing these ligands.

In the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers.

In an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy (RC) were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer (MIBC).

The initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical cystectomy.

Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed.

Programmed cell death-1 (PD-1) inhibitor-related hematologic toxicities are a category of rare but clinically serious and potentially life-threatening adverse events; however, little is known about their risks across different treatment regimens and tumor types.

Anti-PD-1 therapy is increasingly used in various advanced malignancies. Patients with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether anti-PD-1 therapy is safe or effective in this setting.

No data are available on the surgical safety of radical cystectomy (RC) and pelvic lymph node dissection (PLND) after the administration of checkpoint inhibitors. We aimed at reporting the first prospective rigorous assessment of perioperative outcomes after RC and extended PLND following neoadjuvant pembrolizumab in a contemporary cohort of patients with muscle-invasive bladder cancer (MIBC) enrolled in the PURE-01 trial.