Tags

Type your tag names separated by a space and hit enter

A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality.
Clin Genitourin Cancer. 2020 Aug; 18(4):314-321.e1.CG

Abstract

BACKGROUND

Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefits for patients with high-risk nonmetastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade, and histologic type on cancer-specific mortality (CSM) in candidates for 1 of the 4 North American ongoing immune-oncology checkpoint inhibitor trials of high-risk nmRCC.

PATIENTS AND METHODS

From the Surveillance, Epidemiology, and End Results database (2001-2015), we identified patients who had undergone surgery for nmRCC and had met the inclusion criteria for the PROSPER RCC (nivolumab in treating patients with localized kidney cancer undergoing nephrectomy), CheckMate 914 (a study comparing the combination of nivolumab and ipilimumab versus placebo in participants with localized renal cell carcinoma), KEYNOTE-564 [safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy], or IMmotion010 [a study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy] trials. Kaplan-Meier and multivariable Cox regression models were used to assess the 10-year CSM rates in the overall cohort according to stage, grade, and histologic characteristics, and in 4 generated random samples according to the eligible patients for each of the 4 trials.

RESULTS

Of 116,750 patients who had undergone surgery for nmRCC, 18,559 (15.9%) had fulfilled the inclusion criteria for 1 of the 4 trials. The greatest proportion of higher stage and grade combinations and sarcomatoid histologic features would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914, and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for stage N1 grade 3/4 (hazard ratio [HR], 11.5; P < .001), stage T4N0 grade 3/4 (HR, 9.8; P < .001), and sarcomatoid histologic features (HR, 5.5; P < .001). Among the 4 random samples, the difference in the qualifying criteria resulted in the greatest versus progressively lower CSM rates in the IMmotion010, KEYNOTE-564, CheckMate 914, and PROSPER RCC trials, respectively (P < .001).

CONCLUSIONS

Our findings indicate that participation in adjuvant immunotherapy trials should be predominantly encouraged for patients with high-grade stage T3, T4, and N1 and patients with any stage with sarcomatoid pathologic features.

Authors+Show Affiliations

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Urology Unit, ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy. Electronic address: palumbo.carlotta@gmail.com.Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele University, Milan, Italy.Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Department of Urology, European Institute of Oncology, Milan, Italy.Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Martini Klinik, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Division of Urology, University of Montreal Hospital Center, Montreal, QC, Canada.Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern Medical School, Dallas, TX; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Division of Urology, University of Montreal Hospital Center, Montreal, QC, Canada.Division of Urology, Department of Surgery, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Department of Surgery, Université de Montréal, Montréal, QC, Canada.Urology Unit, ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy.Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele University, Milan, Italy.Urology Unit, ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy.Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Division of Urology, University of Montreal Hospital Center, Montreal, QC, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32482565

Citation

Palumbo, Carlotta, et al. "A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality." Clinical Genitourinary Cancer, vol. 18, no. 4, 2020, pp. 314-321.e1.
Palumbo C, Mazzone E, Mistretta FA, et al. A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality. Clin Genitourin Cancer. 2020;18(4):314-321.e1.
Palumbo, C., Mazzone, E., Mistretta, F. A., Knipper, S., Perrotte, P., Shariat, S. F., Saad, F., Kapoor, A., Lattouf, J. B., Simeone, C., Briganti, A., Antonelli, A., & Karakiewicz, P. I. (2020). A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality. Clinical Genitourinary Cancer, 18(4), 314-e1. https://doi.org/10.1016/j.clgc.2019.11.010
Palumbo C, et al. A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality. Clin Genitourin Cancer. 2020;18(4):314-321.e1. PubMed PMID: 32482565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality. AU - Palumbo,Carlotta, AU - Mazzone,Elio, AU - Mistretta,Francesco A, AU - Knipper,Sophie, AU - Perrotte,Paul, AU - Shariat,Shahrokh F, AU - Saad,Fred, AU - Kapoor,Anil, AU - Lattouf,Jean-Baptiste, AU - Simeone,Claudio, AU - Briganti,Alberto, AU - Antonelli,Alessandro, AU - Karakiewicz,Pierre I, Y1 - 2019/12/05/ PY - 2019/08/27/received PY - 2019/11/17/revised PY - 2019/11/27/accepted PY - 2020/6/3/pubmed PY - 2020/6/3/medline PY - 2020/6/3/entrez KW - Adjuvant therapy KW - Clear cell KW - Immune checkpoint inhibitors KW - Nephrectomy KW - Sarcomatoid SP - 314 EP - 321.e1 JF - Clinical genitourinary cancer JO - Clin Genitourin Cancer VL - 18 IS - 4 N2 - BACKGROUND: Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefits for patients with high-risk nonmetastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade, and histologic type on cancer-specific mortality (CSM) in candidates for 1 of the 4 North American ongoing immune-oncology checkpoint inhibitor trials of high-risk nmRCC. PATIENTS AND METHODS: From the Surveillance, Epidemiology, and End Results database (2001-2015), we identified patients who had undergone surgery for nmRCC and had met the inclusion criteria for the PROSPER RCC (nivolumab in treating patients with localized kidney cancer undergoing nephrectomy), CheckMate 914 (a study comparing the combination of nivolumab and ipilimumab versus placebo in participants with localized renal cell carcinoma), KEYNOTE-564 [safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy], or IMmotion010 [a study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy] trials. Kaplan-Meier and multivariable Cox regression models were used to assess the 10-year CSM rates in the overall cohort according to stage, grade, and histologic characteristics, and in 4 generated random samples according to the eligible patients for each of the 4 trials. RESULTS: Of 116,750 patients who had undergone surgery for nmRCC, 18,559 (15.9%) had fulfilled the inclusion criteria for 1 of the 4 trials. The greatest proportion of higher stage and grade combinations and sarcomatoid histologic features would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914, and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for stage N1 grade 3/4 (hazard ratio [HR], 11.5; P < .001), stage T4N0 grade 3/4 (HR, 9.8; P < .001), and sarcomatoid histologic features (HR, 5.5; P < .001). Among the 4 random samples, the difference in the qualifying criteria resulted in the greatest versus progressively lower CSM rates in the IMmotion010, KEYNOTE-564, CheckMate 914, and PROSPER RCC trials, respectively (P < .001). CONCLUSIONS: Our findings indicate that participation in adjuvant immunotherapy trials should be predominantly encouraged for patients with high-grade stage T3, T4, and N1 and patients with any stage with sarcomatoid pathologic features. SN - 1938-0682 UR - https://www.unboundmedicine.com/medline/citation/32482565/A_Plea_for_Optimizing_Selection_in_Current_Adjuvant_Immunotherapy_Trials_for_High-risk_Nonmetastatic_Renal_Cell_Carcinoma_According_to_Expected_Cancer-specific_Mortality L2 - https://www.clinicalkey.com/content/playBy/pii?v=S1558-7673(19)30361-1 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.