Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (accRCC): Results from cohort A of KEYNOTE-427.

McDermott, David F.; Lee, Jae‐Lyun; Szczylik, Cezary; Donskov, Frede; Malik, Jahangeer; Alekseev, Boris; Larkin, James; Матвеев, В. Б.; Gafanov, Rustem; Tomczak, Piotr; Tykodi, Scott S.; Geertsen, Poul F.; Wiechno, Paweł; Shin, Sang Joon; Pouliot, Frédéric; Gordoa, Teresa Alonso; Li, Wenting; Perini, Rodolfo F.; Schloss, Charles; Atkins, Michael B.

doi:10.1200/jco.2018.36.15_suppl.4500

Cited by 85 publications

(54 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is unknown whether the improved outcomes are because this treatment response is being captured in more patients or because the combination augments a response that would not have been seen with either agent alone in sequence. Other trials, such as KEYNOTE‐427, showed a 38% ORR, a 2.7% CR rate, and an 8.7‐month PFS with PD‐1 inhibition alone . The phase 2 clinical trial IMmotion150 compared treatment with atezolizumab alone or in combination with bevacizumab versus sunitinib in patients who had treatment‐naive mRCC.…”

Section: Combining Vegf Inhibitors and Icismentioning

confidence: 89%

“…For patients who had PD‐L1–positive disease with a combined positive score ≥1, the ORR was 50%, with a 6.5% CR rate and a 43.5% PR rate. Grade 3 through 5 treatment‐related AEs occurred in 21.8% of patients …”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…Clinical trials cannot be directly compared given the differences in patient populations and trial methods. Table shows the ORRs, CR rates, PFS, and OS for the key trials in first‐line and second‐line VEGF inhibitor and ICI monotherapy. There are limited data on the activity of single‐agent PD‐1 inhibitors in the first‐line setting, and phase 3 trials of combination therapy did not use single‐agent ICI as a comparison arm; therefore, it is not known which patients benefit from the combination of nivo/ipi versus anti–PD‐1 monotherapy at this time.…”

Section: Combining Versus Sequencing Vegf Inhibitors and Icismentioning

confidence: 99%

“…Grade 3 through 5 treatment-related AEs occurred in 21.8% of patients. 32 Avelumab, an anti-PD-L1 antibody, was studied in a phase 1, open-label, dose-escalation trial as first-line or second-line therapy for patients with advanced solid tumors. In the cohort of 82 patients who had mRCC, 62 received avelumab as first-line treatment, and 20 received it as second-line treatment.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…Other trials, such as KEYNOTE-427, showed a 38% ORR, a 2.7% CR rate, and an 8.7-month PFS with PD-1 inhibition alone. 32 The phase 2 clinical trial IMmotion150 compared treatment with atezolizumab alone or in combination with bevacizumab versus sunitinib in patients who had treatment-naive mRCC. The median PFS was 11.7 months with atezolizumab plus bevacizumab, 8.4 months with sunitinib, and 6.1 months with atezolizumab.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Vascular endothelial growth factor and programmed death‐1 pathway inhibitors in renal cell carcinoma

Mantia

McDermott

2019

Cancer

Self Cite

View full text Add to dashboard Cite

Advanced renal cell carcinoma has historically carried a poor prognosis with very limited treatment options. However, in recent years, the treatment landscape has changed drastically, with many new therapeutic options and improved survival for patients. Novel treatments consist of molecularly targeted agents against the vascular endothelial growth factor (VEGF) pathway as well as the immune checkpoint inhibitors, which stimulate an antitumor immune response. Recent strategy has focused on the development of combination therapy with the use of VEGF inhibitors and immune checkpoint inhibitors in the first‐line setting. As more treatments are approved and the options for therapy expand further, there is a growing need for predictive biomarkers to personalize treatment choices for individual patients. Prospective clinical trials comparing the sequencing of treatments are needed to help determine the best therapeutic approach.

show abstract

Section: Combining Vegf Inhibitors and Icismentioning

confidence: 89%

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Section: Combining Versus Sequencing Vegf Inhibitors and Icismentioning

confidence: 99%

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Vascular endothelial growth factor and programmed death‐1 pathway inhibitors in renal cell carcinoma

Mantia

McDermott

2019

Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

ROS Scavenging Nanozyme Modulates Immunosuppression for Sensitized Cancer Immunotherapy

Liu

Zhao

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Myeloid‐derived suppressor cells (MDSCs) and tumor‐associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC‐induced immunosuppression but also triggers differentiation and polarization of M2‐TAMs. Herein, an ROS scavenging nanozyme, Zr‐CeO, with enhanced superoxide dismutase‐ and catalase‐like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr‐CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2‐TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer‐associated fibroblasts. Furthermore, Zr‐CeO enhances the antitumor effect of PD‐1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr‐CeO alone or combination therapy enhances T lymphocyte infiltration and IFN‐γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided.

show abstract

Immune checkpoint blockade in renal cell carcinoma

Rappold

Silagy

Kotecha

et al. 2021

Journal of Surgical Oncology

View full text Add to dashboard Cite

Immune checkpoint blockade (ICB) is the foundation of current first‐line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long‐lasting remissions. With the expanding arsenal of ICB‐based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.

show abstract

Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (accRCC): Results from cohort A of KEYNOTE-427.

Cited by 85 publications

References 0 publications

Vascular endothelial growth factor and programmed death‐1 pathway inhibitors in renal cell carcinoma

Vascular endothelial growth factor and programmed death‐1 pathway inhibitors in renal cell carcinoma

ROS Scavenging Nanozyme Modulates Immunosuppression for Sensitized Cancer Immunotherapy

Immune checkpoint blockade in renal cell carcinoma

Contact Info

Product

Resources

About