Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIM SM

Clark, Joseph I.; Wong, Michael K.; Kaufman, Howard L.; Daniels, Gregory A.; Morse, Michael A.; McDermott, David F.; Agarwala, Sanjiv S.; Lewis, Lionel D.; Stewart, John H.; Vaishampayan, Ulka N.; Curti, Brendan D.; González, René; Lutzky, Jose; Rudraptna, Venkatesh; Cranmer, Lee D.; Jeter, Joanne; Hauke, Ralph J.; Miletello, Gerald; Milhem, Mohammed; Amin, Asim; Richart, John M.; Fishman, Mayer; Hallmeyer, Sigrun; Patel, Sapna; Veldhuizen, Peter J. Van; Agarwal, Neeraj; Taback, Bret; Treisman, Jonathan; Ernstoff, Marc S.; Perritt, Jessica; Hua, Hong; Rao, Tharak; Dutcher, Janice P.; Aung, Sandra

doi:10.1016/j.clgc.2016.10.008

Cited by 35 publications

(27 citation statements)

References 27 publications

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“…Over the last decade, treatment for metastatic RCC (mRCC) has focused on targeting the VEGF signaling pathway with receptor tyrosine kinase inhibitors, such as sunitinib, or monoclonal antibodies that block VEGF, such as bevacizumab. Although VEGF pathway blockade is effective in many patients, it is associated with development of resistance 3,4 .…”

mentioning

confidence: 99%

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

McDermott

Huseni²,

Atkins³

et al. 2018

Nat Med

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944

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We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19 (95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-1.67), respectively. Exploratory biomarker analyses indicated that tumor mutation and neoantigen burden were not associated with PFS. Angiogenesis, T-effector/IFN-γ response, and myeloid inflammatory gene expression signatures were strongly and differentially associated with PFS within and across the treatments. These molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade.

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mentioning

confidence: 99%

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

McDermott

Huseni²,

Atkins³

et al. 2018

Nat Med

Self Cite

1,003

944

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“…RCC is a heterogenous cancer, and its progression is influenced by various factors [10]. Although immunotherapy has been used for the treatment of RCC patients, the associated therapeutic effects have proven to be insufficient in few patients, due to low efficacy and high toxicity [11].…”

Section: Discussionmentioning

confidence: 99%

FSIP2 can serve as a predictive biomarker for Clear Cell Renal Cell Carcinoma prognosis

et al. 2020

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To characterize the role of fibrous sheath interacting protein 2 (FSIP2) in the survival outcomes and prognosis of clear cell renal cell carcinoma (ccRCC) patients, which is currently not well understood. Methods: The Oncomine and CCLE databases were used to investigate the differential expression of FSIP2 in ccRCC versus other cancer types. Levels of FSIP2 in 85 ccRCC patients were assessed by immunohistochemical analysis; clinicopathological features related to FSIP2 expression were examined in these patients finally, disease-free survival and overall survival were estimated by survival analysis to elucidate the impact of FSIP2 expression in ccRCC patients. Results: Analysis using the Oncomine database revealed significant upregulation of the FSIP2 gene in papillary RCC, compared to that in normal tissues. Additionally, FSIP2 expression was found to be significantly associated with abnormal platelet count, positive distant metastasis, and death as the incidence of distant metastasis and death were higher in patients with FSIP2 expression compared to those without FSIP2 expression. Survival analysis revealed that FSIP2 expression was significantly related to shorter disease-free survival and overall survival. Meanwhile, patients with FSIP2 expression had worse prognosis than those without FSIP2 expression. Conclusions: FSIP2 expression is associated with poor survival outcomes and poor prognosis in ccRCC patients. FSIP2 may therefore serve as a potential predictive biomarker of ccRCC prognosis.

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“…25 Historically, RCC has been known to be immunogenic and immunoresponsive, with low levels (5%-8%) of durable complete responses to high-dose interleukin (IL)-2. 26,27 Durable complete responses are rare (1%) with VEGF-targeted strategies alone in mRCC. 13,22 The advent of CPIs for treatment of various solid tumors has offered much promise, given the immune system's capacity for memory and its exquisite specificity.…”

Section: Immuno-oncology Therapies For Mrccmentioning

confidence: 99%

Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma

Labriola

Batich

Zhu

et al. 2019

Clinical Genitourinary Cancer

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The incidence of renal-cell carcinoma has been increasing each year, with nearly one third of new cases diagnosed at advanced or metastatic stage. The advent of targeted therapies for metastatic renal-cell carcinoma (mRCC) has underscored the need to subtype tumors according to tumorimmune expression profiles that may more reliably predict treatment outcomes. Over the past 2 decades, several vascular endothelial growth factor (VEGF) and tyrosine kinase inhibitors have been the mainstay for first-and second-line treatment of mRCC. Very recently, immunotherapy checkpoint inhibitors have significantly changed the treatment landscape for patients with mRCC, particularly for first-line treatment of intermediate to poor risk mRCC patients. Now, combination immunotherapy as well as combinations of immunotherapy with targeted agents can significantly alter disease outcomes. The field of immuno-oncology for mRCC has unveiled a deeper understanding of the immunoreactivity inherent to these tumors, and as a result combination therapy is evolving as a first-line modality. This review provides a timeline of advances and controversies in first-line treatment of mRCC, describes recent advances in understanding the immunoreactivity of these tumors, and addresses the future of combination anti-VEGF and immunotherapeutic platforms.

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Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIM SM

Cited by 35 publications

References 27 publications

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

FSIP2 can serve as a predictive biomarker for Clear Cell Renal Cell Carcinoma prognosis

Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma

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