Skip to main content
Top
Published in:

01-10-2024 | Kidney Cancer | Review

Turning the tide: pembrolizumab’s triumph in adjuvant RCC therapy

Authors: Fouad Attieh, Marc Boutros, Hampig Raphaël Kourie, Mervat Mahrous

Published in: Medical Oncology | Issue 10/2024

Login to get access

Abstract

In recent years, kidney cancer has shown an increased worldwide incidence of more than 400 000 novel cases annually. Although more than half of patients are diagnosed at a localised stage, this disease presents a high-risk of relapse after surgery. Thus, there is a need for adjuvant therapy post-resection to reduce cancer recurrence and prolong disease-free and overall survival. Thorough investigation of adjuvant drugs for renal cell carcinoma (RCC) has shown little promise in the last fifty years, with no recorded overall survival benefits. This was the case until pembrolizumab, an immune checkpoint inhibitor, was introduced into the adjuvant RCC space through the KEYNOTE-564 trial. The adjuvant administration of this novel anti-PD-1 drug demonstrated a significant overall survival benefit which has led to an update in the current treatment guidelines of RCC. This substantial change in the standard of care also caused an investigation of possible treatment combinations and an adoption of innovative predictive biomarkers. In this review, we will present the evolution of past adjuvant ICI trials for the treatment of RCC, the implications of pembrolizumab’s overall survival benefits and a discussion of future directions concerning new RCC drug trials and liquid biopsy-based biomarkers.
Literature
9.
go back to reference Şenbabaoğlu Y, Gejman RS, Winer AG, Liu M, Van Allen EM, de Velasco G, Miao D, Ostrovnaya I, Drill E, Luna A, Weinhold N, Lee W, Manley BJ, Khalil DN, Kaffenberger SD, Chen Y, Danilova L, Voss MH, Coleman JA, Russo P, Reuter VE, Chan TA, Cheng EH, Scheinberg DA, Li MO, Choueiri TK, Hsieh JJ, Sander C, Hakimi AA. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 2016;17:231. https://doi.org/10.1186/s13059-016-1092-z.CrossRefPubMedPubMedCentral Şenbabaoğlu Y, Gejman RS, Winer AG, Liu M, Van Allen EM, de Velasco G, Miao D, Ostrovnaya I, Drill E, Luna A, Weinhold N, Lee W, Manley BJ, Khalil DN, Kaffenberger SD, Chen Y, Danilova L, Voss MH, Coleman JA, Russo P, Reuter VE, Chan TA, Cheng EH, Scheinberg DA, Li MO, Choueiri TK, Hsieh JJ, Sander C, Hakimi AA. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 2016;17:231. https://​doi.​org/​10.​1186/​s13059-016-1092-z.CrossRefPubMedPubMedCentral
11.
go back to reference Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang Y-H, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T. KEYNOTE-426 Investigators: pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27. https://doi.org/10.1056/NEJMoa1816714.CrossRefPubMed Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang Y-H, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T. KEYNOTE-426 Investigators: pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27. https://​doi.​org/​10.​1056/​NEJMoa1816714.CrossRefPubMed
12.
go back to reference Motzer R, Alekseev B, Rha S-Y, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong S-H, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK. CLEAR trial investigators: lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384:1289–300. https://doi.org/10.1056/NEJMoa2035716.CrossRefPubMed Motzer R, Alekseev B, Rha S-Y, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong S-H, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK. CLEAR trial investigators: lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384:1289–300. https://​doi.​org/​10.​1056/​NEJMoa2035716.CrossRefPubMed
13.
go back to reference Pal SK, Uzzo R, Karam JA, Master VA, Donskov F, Suarez C, Albiges L, Rini B, Tomita Y, Kann AG, Procopio G, Massari F, Zibelman M, Antonyan I, Huseni M, Basu D, Ci B, Leung W, Khan O, Dubey S, Bex A. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2022;400:1103–16. https://doi.org/10.1016/S0140-6736(22)01658-0.CrossRefPubMed Pal SK, Uzzo R, Karam JA, Master VA, Donskov F, Suarez C, Albiges L, Rini B, Tomita Y, Kann AG, Procopio G, Massari F, Zibelman M, Antonyan I, Huseni M, Basu D, Ci B, Leung W, Khan O, Dubey S, Bex A. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2022;400:1103–16. https://​doi.​org/​10.​1016/​S0140-6736(22)01658-0.CrossRefPubMed
14.
go back to reference Motzer RJ, Russo P, Grünwald V, Tomita Y, Zurawski B, Parikh O, Buti S, Barthélémy P, Goh JC, Ye D, Lingua A, Lattouf J-B, Albigès L, George S, Shuch B, Sosman J, Staehler M, Estévez SV, Simsek B, Spiridigliozzi J, Chudnovsky A, Bex A. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial. Lancet. 2023;401:821–32. https://doi.org/10.1016/S0140-6736(22)02574-0.CrossRefPubMedPubMedCentral Motzer RJ, Russo P, Grünwald V, Tomita Y, Zurawski B, Parikh O, Buti S, Barthélémy P, Goh JC, Ye D, Lingua A, Lattouf J-B, Albigès L, George S, Shuch B, Sosman J, Staehler M, Estévez SV, Simsek B, Spiridigliozzi J, Chudnovsky A, Bex A. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial. Lancet. 2023;401:821–32. https://​doi.​org/​10.​1016/​S0140-6736(22)02574-0.CrossRefPubMedPubMedCentral
15.
go back to reference Motzer RJ, Bex A, Russo P, Tomita Y, Cutuli H, Rojas C, Gross-Goupil M, Schinzari G, Melichar B, Barthelemy P, Ruiz Garcia A, Sosman JA, Grimm M-O, Goh JC, Suárez C, Kollmannsberger CK, Simsek B, Spiridigliozzi J, Lee C-W, Grünwald V. Adjuvant nivolumab monotherapy vs placebo for localized renal cell carcinoma at high risk of relapse after nephrectomy: results from part B of the randomized, phase 3 CheckMate 914 trial. JCO. 2024. https://doi.org/10.1200/JCO.2024.42.4_suppl.LBA358.CrossRef Motzer RJ, Bex A, Russo P, Tomita Y, Cutuli H, Rojas C, Gross-Goupil M, Schinzari G, Melichar B, Barthelemy P, Ruiz Garcia A, Sosman JA, Grimm M-O, Goh JC, Suárez C, Kollmannsberger CK, Simsek B, Spiridigliozzi J, Lee C-W, Grünwald V. Adjuvant nivolumab monotherapy vs placebo for localized renal cell carcinoma at high risk of relapse after nephrectomy: results from part B of the randomized, phase 3 CheckMate 914 trial. JCO. 2024. https://​doi.​org/​10.​1200/​JCO.​2024.​42.​4_​suppl.​LBA358.CrossRef
16.
go back to reference Allaf M, Kim SE, Harshman LC, McDermott DF, Master VA, Signoretti S, Cole S, Moon H, Adra N, Singer EA, Gills J, Choueiri TK, Leibovich B, Michaelson MD, Shuch B, Lara PN, Heng DYC, Kapoor A, Carducci MA, Haas NB. LBA67 phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a national clinical trials network trial. Ann Oncol. 2022;33:S1432–3. https://doi.org/10.1016/j.annonc.2022.08.072.CrossRef Allaf M, Kim SE, Harshman LC, McDermott DF, Master VA, Signoretti S, Cole S, Moon H, Adra N, Singer EA, Gills J, Choueiri TK, Leibovich B, Michaelson MD, Shuch B, Lara PN, Heng DYC, Kapoor A, Carducci MA, Haas NB. LBA67 phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a national clinical trials network trial. Ann Oncol. 2022;33:S1432–3. https://​doi.​org/​10.​1016/​j.​annonc.​2022.​08.​072.CrossRef
17.
go back to reference Choueiri TK, Quinn DI, Zhang T, Gurney H, Doshi GK, Cobb PW, Parnis F, Lee J-L, Park SH, Semenov A, Thiery-Vuillemin A, Sawrycki P, Tomczak P, Alekseev B, Izmailov A, Chang WY-H, Wan SM, Poehlein CH, Willemann-Rogerio J, Powles T. Abstract CT162: pembrolizumab monotherapy for the adjuvant treatment of renal cell carcinoma post-nephrectomy: randomized, double-blind, phase III KEYNOTE-564 study. Cancer Res. 2019. https://doi.org/10.1158/1538-7445.AM2019-CT162.CrossRef Choueiri TK, Quinn DI, Zhang T, Gurney H, Doshi GK, Cobb PW, Parnis F, Lee J-L, Park SH, Semenov A, Thiery-Vuillemin A, Sawrycki P, Tomczak P, Alekseev B, Izmailov A, Chang WY-H, Wan SM, Poehlein CH, Willemann-Rogerio J, Powles T. Abstract CT162: pembrolizumab monotherapy for the adjuvant treatment of renal cell carcinoma post-nephrectomy: randomized, double-blind, phase III KEYNOTE-564 study. Cancer Res. 2019. https://​doi.​org/​10.​1158/​1538-7445.​AM2019-CT162.CrossRef
18.
go back to reference Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang Y-H, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385:683–94. https://doi.org/10.1056/NEJMoa2106391.CrossRefPubMed Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang Y-H, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385:683–94. https://​doi.​org/​10.​1056/​NEJMoa2106391.CrossRefPubMed
22.
go back to reference Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang Y-H, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK, Tomczak P, Choueiri T, Park SH, Venugopal B, Ferguson TR, Hajek J, Lin T-P, Symeonides SN, Lee JL, Sawrycki P, Haas NB, Gurney HP, Mahave M, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Chevreau C, Burke JM, Doshi G, Melichar B, Topart D, Oudard S, Kopyltsov E, Hammers H-J, Quinn DI, Alva A, de Menezes J, Silva AG, Winquist EW, Hamzaj A, Procopio G, Karaszewska B, Nowakowska-Zajdel EM, Alekseev BY, Gafanov RA, Izmailov A, Semenov A, Afanasyev SG, Lipatov ON, Powles TB, Srinivas S, McDermott D, Kochuparambil ST, Davis ID, Peltola K, Sabbatini R, Chung J, Shkolnik MI, Matveev VB, Borau PG, McCune S, Hutson TE, Dri A, Sales SC, Yeung C, Castro CMA, Bostrom P, Laguerre B, Buttigliero C, de Giorgi U, Fomin EA, Zakharia Y, Hwang C, Singer EA, Yorio JT, Waterhouse D, Kowalyszyn RD, Alfie MS, Ruiz EY, Buchler T, Kankaanranta K, Ferretti G, Kimura G, Nishimura K, Masumori N, Tamada S, Kato H, Kitamura H, Danielewicz I, Wojcik-Tomaszewska J, Gonzalez NS, Chiu K-Y, Atkins MB, Heath E, Rojas-Uribe GA, Fernandez MEG, Feyerabend S, Pignata S, Numakura K, Stopa BC, Zukov R, Duran MAC, Rey PJM, Pino AM, Chang C-H, Vengalil S, Waddell TS, Cobb PW, Hauke R, Anderson DM, Sarantopoulos J, Gourdin T, Zhang T, Jayram G, Fein LE, Harris C, Beato PMM, Flores F, Estay A, Rubiano JA, Bedke J, Hauser S, Neisius A, Busch J, Anai S, Tsunemori H, Sawka D, Sikora-Kupis B, Arranz JA, Delgado I, Chen C-H, Gunderson E, Tykodi S, Koletsky A, Chen K, Agrawal M, Kaen DL, Sade JP, Tatangelo MD, Parnis F, Barbosa FM, Faucher G, Iqbal N, Marceau D, Paradis J-B, Hanna N, Acevedo A, Ibanez C, Villanueva L, Galaz PP, Durango IC, Manneh R, Kral Z, Holeckova P, Hakkarainen H, Ronkainen H, Abadie-Lacourtoisie S, Tartas S, Goebell PJ, Grimm M-O, Hoefner T, Wirth M, Panic A, Schultze-Seemann W, Yokomizo A, Mizuno R, Uemura H, Eto M, Tsujihata M, Matsukawa Y, Murakami Y, Kim M, Hamberg P, Marczewska-Skrodzka M, Szczylik C, Humphreys AC, Jiang P, Kumar B, Lu G, Desai A, Karam JA, Keogh G, Fleming M, Zarba JJ, Leiva VE, Mendez GA, Harris SJ, Brown SJ, Junior JNA, de Costamilan R, Rocha RO, Muniz D, Brust L, Lalani A-K, Graham J, Levesque M, Orlandi F, Kotasek R, Deville JL, Borchiellini D, Merseburger A, Rink M, Roos F, McDermott R, Oyama M, Yamamoto Y, Tomita Y, Miura Y, Ioritani N, Westgeest H, Kubiatowski T, Bal W, Sarrio RG, Rowe J, Prow DM, Senecal F, Hashemi-Sadraei N, Cole SW, Kendall SD, Richards DA, Schnadig ID, Gupta M. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23:1133–44. https://doi.org/10.1016/S1470-2045(22)00487-9.CrossRefPubMed Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang Y-H, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK, Tomczak P, Choueiri T, Park SH, Venugopal B, Ferguson TR, Hajek J, Lin T-P, Symeonides SN, Lee JL, Sawrycki P, Haas NB, Gurney HP, Mahave M, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Chevreau C, Burke JM, Doshi G, Melichar B, Topart D, Oudard S, Kopyltsov E, Hammers H-J, Quinn DI, Alva A, de Menezes J, Silva AG, Winquist EW, Hamzaj A, Procopio G, Karaszewska B, Nowakowska-Zajdel EM, Alekseev BY, Gafanov RA, Izmailov A, Semenov A, Afanasyev SG, Lipatov ON, Powles TB, Srinivas S, McDermott D, Kochuparambil ST, Davis ID, Peltola K, Sabbatini R, Chung J, Shkolnik MI, Matveev VB, Borau PG, McCune S, Hutson TE, Dri A, Sales SC, Yeung C, Castro CMA, Bostrom P, Laguerre B, Buttigliero C, de Giorgi U, Fomin EA, Zakharia Y, Hwang C, Singer EA, Yorio JT, Waterhouse D, Kowalyszyn RD, Alfie MS, Ruiz EY, Buchler T, Kankaanranta K, Ferretti G, Kimura G, Nishimura K, Masumori N, Tamada S, Kato H, Kitamura H, Danielewicz I, Wojcik-Tomaszewska J, Gonzalez NS, Chiu K-Y, Atkins MB, Heath E, Rojas-Uribe GA, Fernandez MEG, Feyerabend S, Pignata S, Numakura K, Stopa BC, Zukov R, Duran MAC, Rey PJM, Pino AM, Chang C-H, Vengalil S, Waddell TS, Cobb PW, Hauke R, Anderson DM, Sarantopoulos J, Gourdin T, Zhang T, Jayram G, Fein LE, Harris C, Beato PMM, Flores F, Estay A, Rubiano JA, Bedke J, Hauser S, Neisius A, Busch J, Anai S, Tsunemori H, Sawka D, Sikora-Kupis B, Arranz JA, Delgado I, Chen C-H, Gunderson E, Tykodi S, Koletsky A, Chen K, Agrawal M, Kaen DL, Sade JP, Tatangelo MD, Parnis F, Barbosa FM, Faucher G, Iqbal N, Marceau D, Paradis J-B, Hanna N, Acevedo A, Ibanez C, Villanueva L, Galaz PP, Durango IC, Manneh R, Kral Z, Holeckova P, Hakkarainen H, Ronkainen H, Abadie-Lacourtoisie S, Tartas S, Goebell PJ, Grimm M-O, Hoefner T, Wirth M, Panic A, Schultze-Seemann W, Yokomizo A, Mizuno R, Uemura H, Eto M, Tsujihata M, Matsukawa Y, Murakami Y, Kim M, Hamberg P, Marczewska-Skrodzka M, Szczylik C, Humphreys AC, Jiang P, Kumar B, Lu G, Desai A, Karam JA, Keogh G, Fleming M, Zarba JJ, Leiva VE, Mendez GA, Harris SJ, Brown SJ, Junior JNA, de Costamilan R, Rocha RO, Muniz D, Brust L, Lalani A-K, Graham J, Levesque M, Orlandi F, Kotasek R, Deville JL, Borchiellini D, Merseburger A, Rink M, Roos F, McDermott R, Oyama M, Yamamoto Y, Tomita Y, Miura Y, Ioritani N, Westgeest H, Kubiatowski T, Bal W, Sarrio RG, Rowe J, Prow DM, Senecal F, Hashemi-Sadraei N, Cole SW, Kendall SD, Richards DA, Schnadig ID, Gupta M. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23:1133–44. https://​doi.​org/​10.​1016/​S1470-2045(22)00487-9.CrossRefPubMed
23.
go back to reference Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang Y-H, Lee J-L, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Zhang T, Xu L, Imai K, Poehlein CH, Powles T. Adjuvant pembrolizumab (pembro) for renal cell carcinoma (RCC) across UCLA Integrated Staging System (UISS) risk groups and disease stage: subgroup analyses from the KEYNOTE-564 study. JCO. 2023;41:679. https://doi.org/10.1200/JCO.2023.41.6_suppl.679.CrossRef Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang Y-H, Lee J-L, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Zhang T, Xu L, Imai K, Poehlein CH, Powles T. Adjuvant pembrolizumab (pembro) for renal cell carcinoma (RCC) across UCLA Integrated Staging System (UISS) risk groups and disease stage: subgroup analyses from the KEYNOTE-564 study. JCO. 2023;41:679. https://​doi.​org/​10.​1200/​JCO.​2023.​41.​6_​suppl.​679.CrossRef
25.
go back to reference Bedke J, Albiges L, Capitanio U, Giles RH, Hora M, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, Bex A. The 2022 updated European association of urology guidelines on the use of adjuvant immune checkpoint inhibitor therapy for renal cell carcinoma. Eur Urol. 2023;83:10–4. https://doi.org/10.1016/j.eururo.2022.10.010.CrossRefPubMed Bedke J, Albiges L, Capitanio U, Giles RH, Hora M, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, Bex A. The 2022 updated European association of urology guidelines on the use of adjuvant immune checkpoint inhibitor therapy for renal cell carcinoma. Eur Urol. 2023;83:10–4. https://​doi.​org/​10.​1016/​j.​eururo.​2022.​10.​010.CrossRefPubMed
26.
go back to reference Choueiri TK, Tomczak P, Park SH, Venugopal B, Symeonides S, Hajek J, Ferguson T, Chang Y-H, Lee JL, Haas N, Sawrycki P, Sarwar N, Gross-Goupil M, Thiery-Vuillemin A, Mahave M, Kimura G, Perini RF, Saretsky TL, Bhattacharya R, Xu L, Powles T. Patient-reported outcomes in KEYNOTE-564: adjuvant pembrolizumab versus placebo for renal cell carcinoma. Oncol. 2023. https://doi.org/10.1093/oncolo/oyad231.CrossRef Choueiri TK, Tomczak P, Park SH, Venugopal B, Symeonides S, Hajek J, Ferguson T, Chang Y-H, Lee JL, Haas N, Sawrycki P, Sarwar N, Gross-Goupil M, Thiery-Vuillemin A, Mahave M, Kimura G, Perini RF, Saretsky TL, Bhattacharya R, Xu L, Powles T. Patient-reported outcomes in KEYNOTE-564: adjuvant pembrolizumab versus placebo for renal cell carcinoma. Oncol. 2023. https://​doi.​org/​10.​1093/​oncolo/​oyad231.CrossRef
27.
go back to reference Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang Y-H, Lee J-L, Sarwar N, Gurney H, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Zhang T, Cornell J, Elfiky A, Burgents JE, Powles T. Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC). JCO. 2024. https://doi.org/10.1200/JCO.2024.42.4_suppl.LBA359.CrossRef Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang Y-H, Lee J-L, Sarwar N, Gurney H, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Zhang T, Cornell J, Elfiky A, Burgents JE, Powles T. Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC). JCO. 2024. https://​doi.​org/​10.​1200/​JCO.​2024.​42.​4_​suppl.​LBA359.CrossRef
28.
go back to reference Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang Y-H, Lee J-L, Sarwar N, Haas NB, Gurney H, Sawrycki P, Mahave M, Gross-Goupil M, Zhang T, Burke JM, Doshi G, Melichar B, Kopyltsov E, Alva A, Oudard S, Topart D, Hammers H, Kitamura H, McDermott DF, Silva A, Winquist E, Cornell J, Elfiky A, Burgents JE, Perini RF, Powles T. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390:1359–71.CrossRefPubMed Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang Y-H, Lee J-L, Sarwar N, Haas NB, Gurney H, Sawrycki P, Mahave M, Gross-Goupil M, Zhang T, Burke JM, Doshi G, Melichar B, Kopyltsov E, Alva A, Oudard S, Topart D, Hammers H, Kitamura H, McDermott DF, Silva A, Winquist E, Cornell J, Elfiky A, Burgents JE, Perini RF, Powles T. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390:1359–71.CrossRefPubMed
30.
go back to reference Oza B, Frangou E, Smith B, Bryant H, Kaplan R, Choodari-Oskooei B, Powles T, Stewart GD, Albiges L, Bex A, Choueiri TK, Davis ID, Eisen T, Fielding A, Harrison D, McWhirter A, Mulhere S, Nathan P, Rini B, Ritchie A, Scovell S, Shakeshaft C, Stockler MR, Thorogood N, Parmar MKB, Larkin J, Meade A. RAMPART: a phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse. Contemp Clin Trials. 2021;108:106482. https://doi.org/10.1016/j.cct.2021.106482.CrossRefPubMedPubMedCentral Oza B, Frangou E, Smith B, Bryant H, Kaplan R, Choodari-Oskooei B, Powles T, Stewart GD, Albiges L, Bex A, Choueiri TK, Davis ID, Eisen T, Fielding A, Harrison D, McWhirter A, Mulhere S, Nathan P, Rini B, Ritchie A, Scovell S, Shakeshaft C, Stockler MR, Thorogood N, Parmar MKB, Larkin J, Meade A. RAMPART: a phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse. Contemp Clin Trials. 2021;108:106482. https://​doi.​org/​10.​1016/​j.​cct.​2021.​106482.CrossRefPubMedPubMedCentral
32.
go back to reference Iacovelli R, Fantinel E, Bimbatti D, Buti S, Bonomi L, Rizzo M, Accettura C, Buttigliero C, Massari F, Santoni M, Zucali PA, Zanardi E, Mosca A, Primi F, Spina F, Procopio G, Bracarda S, Calabrò F, Antonuzzo L, Ciccarese C. Efficacy of perioperative pembrolizumab treatment in patients with resectable metastases from kidney cancer: the PE-PE study. JCO. 2024. https://doi.org/10.1200/JCO.2024.42.4_suppl.TPS495.CrossRef Iacovelli R, Fantinel E, Bimbatti D, Buti S, Bonomi L, Rizzo M, Accettura C, Buttigliero C, Massari F, Santoni M, Zucali PA, Zanardi E, Mosca A, Primi F, Spina F, Procopio G, Bracarda S, Calabrò F, Antonuzzo L, Ciccarese C. Efficacy of perioperative pembrolizumab treatment in patients with resectable metastases from kidney cancer: the PE-PE study. JCO. 2024. https://​doi.​org/​10.​1200/​JCO.​2024.​42.​4_​suppl.​TPS495.CrossRef
35.
go back to reference Braun DA, Keskin DB, Shukla SA, McGregor BA, Schindler NR, Blass E, Klaeger S, Pomerance L, Sarkizova S, Li S, Southard J, Moranzoni G, Pedersen CB, Liu Y, Chang SL, Hirsch MS, LeBoeuf NR, Mossanen M, Chea V, Carulli I, Olive O, Mehndiratta A, Greenslade H, Oliveira G, Iorgulescu JB, Signoretti S, Aster JC, Elagina L, Leshchiner I, Getz G, Harden M, Gabriel S, Olsen LR, Neuberg DS, Fritsch EF, Hacohen N, Livak KJ, Carr S, Ott PA, Wu CJ, Choueiri TK. Abstract PR015: tumor-specific immunity generated by a personalized neoantigen vaccination incorporating locally delivered ipilimumab in renal cell carcinoma. Cancer Res. 2023. https://doi.org/10.1158/1538-7445.KIDNEY23-PR015.CrossRef Braun DA, Keskin DB, Shukla SA, McGregor BA, Schindler NR, Blass E, Klaeger S, Pomerance L, Sarkizova S, Li S, Southard J, Moranzoni G, Pedersen CB, Liu Y, Chang SL, Hirsch MS, LeBoeuf NR, Mossanen M, Chea V, Carulli I, Olive O, Mehndiratta A, Greenslade H, Oliveira G, Iorgulescu JB, Signoretti S, Aster JC, Elagina L, Leshchiner I, Getz G, Harden M, Gabriel S, Olsen LR, Neuberg DS, Fritsch EF, Hacohen N, Livak KJ, Carr S, Ott PA, Wu CJ, Choueiri TK. Abstract PR015: tumor-specific immunity generated by a personalized neoantigen vaccination incorporating locally delivered ipilimumab in renal cell carcinoma. Cancer Res. 2023. https://​doi.​org/​10.​1158/​1538-7445.​KIDNEY23-PR015.CrossRef
39.
go back to reference Powles T, Assaf ZJ, Davarpanah N, Banchereau R, Szabados BE, Yuen KC, Grivas P, Hussain M, Oudard S, Gschwend JE, Albers P, Castellano D, Nishiyama H, Daneshmand S, Sharma S, Zimmermann BG, Sethi H, Aleshin A, Perdicchio M, Zhang J, Shames DS, Degaonkar V, Shen X, Carter C, Bais C, Bellmunt J, Mariathasan S. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. 2021;595:432–7. https://doi.org/10.1038/s41586-021-03642-9.CrossRefPubMed Powles T, Assaf ZJ, Davarpanah N, Banchereau R, Szabados BE, Yuen KC, Grivas P, Hussain M, Oudard S, Gschwend JE, Albers P, Castellano D, Nishiyama H, Daneshmand S, Sharma S, Zimmermann BG, Sethi H, Aleshin A, Perdicchio M, Zhang J, Shames DS, Degaonkar V, Shen X, Carter C, Bais C, Bellmunt J, Mariathasan S. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. 2021;595:432–7. https://​doi.​org/​10.​1038/​s41586-021-03642-9.CrossRefPubMed
41.
go back to reference Yamamoto Y, Uemura M, Fujita M, Maejima K, Koh Y, Matsushita M, Nakano K, Hayashi Y, Wang C, Ishizuya Y, Kinouchi T, Hayashi T, Matsuzaki K, Jingushi K, Kato T, Kawashima A, Ujike T, Nagahara A, Fujita K, Imamura R, Nakagawa H, Nonomura N. Clinical significance of the mutational landscape and fragmentation of circulating tumor DNA in renal cell carcinoma. Cancer Sci. 2019;110:617–28. https://doi.org/10.1111/cas.13906.CrossRefPubMedPubMedCentral Yamamoto Y, Uemura M, Fujita M, Maejima K, Koh Y, Matsushita M, Nakano K, Hayashi Y, Wang C, Ishizuya Y, Kinouchi T, Hayashi T, Matsuzaki K, Jingushi K, Kato T, Kawashima A, Ujike T, Nagahara A, Fujita K, Imamura R, Nakagawa H, Nonomura N. Clinical significance of the mutational landscape and fragmentation of circulating tumor DNA in renal cell carcinoma. Cancer Sci. 2019;110:617–28. https://​doi.​org/​10.​1111/​cas.​13906.CrossRefPubMedPubMedCentral
43.
go back to reference Correa A, Connolly DC, Balcioglu M, Wu H-T, Dashner S, Shchegrova S, Kalashnikova E, Pawar H, Uzzo RG, Gong Y, Kister D, Collins M, Donovan M, Winters R, Aleshin A, Sethi H, Salari R, Louie M, Zimmermann B, Abbosh P. 110P - presence of circulating tumour DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis. Ann Oncol. 2019. https://doi.org/10.1093/annonc/mdz239.021.CrossRef Correa A, Connolly DC, Balcioglu M, Wu H-T, Dashner S, Shchegrova S, Kalashnikova E, Pawar H, Uzzo RG, Gong Y, Kister D, Collins M, Donovan M, Winters R, Aleshin A, Sethi H, Salari R, Louie M, Zimmermann B, Abbosh P. 110P - presence of circulating tumour DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis. Ann Oncol. 2019. https://​doi.​org/​10.​1093/​annonc/​mdz239.​021.CrossRef
48.
go back to reference Nuzzo PV, Berchuck JE, Korthauer K, Spisak S, Nassar AH, Abou Alaiwi S, Chakravarthy A, Shen SY, Bakouny Z, Boccardo F, Steinharter J, Bouchard G, Curran CR, Pan W, Baca SC, Seo J-H, Lee G-SM, Michaelson MD, Chang SL, Waikar SS, Sonpavde G, Irizarry RA, Pomerantz M, De Carvalho DD, Choueiri TK, Freedman ML. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med. 2020;26:1041–3. https://doi.org/10.1038/s41591-020-0933-1.CrossRefPubMedPubMedCentral Nuzzo PV, Berchuck JE, Korthauer K, Spisak S, Nassar AH, Abou Alaiwi S, Chakravarthy A, Shen SY, Bakouny Z, Boccardo F, Steinharter J, Bouchard G, Curran CR, Pan W, Baca SC, Seo J-H, Lee G-SM, Michaelson MD, Chang SL, Waikar SS, Sonpavde G, Irizarry RA, Pomerantz M, De Carvalho DD, Choueiri TK, Freedman ML. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med. 2020;26:1041–3. https://​doi.​org/​10.​1038/​s41591-020-0933-1.CrossRefPubMedPubMedCentral
49.
go back to reference Büttner T, Zarbl R, Krausewitz P, Strieth S, Kristiansen G, Ralser DJ, Hölzel M, Ritter M, Ellinger J, Dietrich D. Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk. Am J Transl Res. 2024;16:304.CrossRefPubMedPubMedCentral Büttner T, Zarbl R, Krausewitz P, Strieth S, Kristiansen G, Ralser DJ, Hölzel M, Ritter M, Ellinger J, Dietrich D. Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk. Am J Transl Res. 2024;16:304.CrossRefPubMedPubMedCentral
50.
go back to reference Rini BI, Zhang J, Hall O, Bergener J, Wang Y, Brown B, Min J, Shen SY, Fleshner N, Polio A, Sosa E, Bratman S, Allen B, Brown K, Licon A, Hartman A-R, Carvalho DDD, Park BH, Liu G. 1910P Evaluation of a genome-wide methylome enrichment platform for circulating tumor DNA quantification and prognostic performance in renal cell carcinoma (RCC). Ann Oncol. 2023;34:S1028. https://doi.org/10.1016/j.annonc.2023.09.1140.CrossRef Rini BI, Zhang J, Hall O, Bergener J, Wang Y, Brown B, Min J, Shen SY, Fleshner N, Polio A, Sosa E, Bratman S, Allen B, Brown K, Licon A, Hartman A-R, Carvalho DDD, Park BH, Liu G. 1910P Evaluation of a genome-wide methylome enrichment platform for circulating tumor DNA quantification and prognostic performance in renal cell carcinoma (RCC). Ann Oncol. 2023;34:S1028. https://​doi.​org/​10.​1016/​j.​annonc.​2023.​09.​1140.CrossRef
Metadata
Title
Turning the tide: pembrolizumab’s triumph in adjuvant RCC therapy
Authors
Fouad Attieh
Marc Boutros
Hampig Raphaël Kourie
Mervat Mahrous
Publication date
01-10-2024
Publisher
Springer US
Published in
Medical Oncology / Issue 10/2024
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02486-3

Other articles of this Issue 10/2024

Medical Oncology 10/2024 Go to the issue

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more