Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy
Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC)...
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| Veröffentlicht in: | European journal of cancer (1990) 2022-08, Vol.171, p.124-132 |
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| creator | Graham, Jeffrey Wells, John Connor Dudani, Shaan Gan, Chun L. Donskov, Frede Lee, Jae-lyun Kollmannsberger, Christian K. Meza, Luis Beuselinck, Benoit Hansen, Aaron North, Scott A. Bjarnason, Georg A. Sayegh, Nicolas Kanesvaran, Ravindran Wood, Lori A. Hotte, Sebastien J. McKay, Rana R. Choueiri, Toni K. Heng, Daniel Y.C. |
| description | Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited.
We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan–Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates.
We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42–0.78, p |
| doi_str_mv | 10.1016/j.ejca.2022.05.002 |
| format | Article |
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We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan–Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates.
We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42–0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36–0.71, p < 0.0001) for ICI versus mTOR.
In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.
•Non-clear cell RCC refers to a group of diverse kidney cancer subtypes.•Evidence for immune checkpoint inhibitor (ICI) use in nccRCC is limited.•Based on this retrospective study, first-line ICI therapy has activity in nccRCC.•The benefit was driven primarily by the papillary RCC subgroup.•Our results should be confirmed in prospective trials in variant histology RCC.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2022.05.002</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Clear cell-type renal cell carcinoma ; Clinical trials ; Growth factors ; Hazard identification ; Immune checkpoint inhibitor ; Immune checkpoint inhibitors ; Immunotherapy ; Inhibitors ; Kidney cancer ; Metastases ; Metastasis ; Non-clear cell RCC ; Patients ; Rapamycin ; Renal cell carcinoma ; Statistical models ; Therapy ; TOR protein ; Variant histology RCC ; Vascular endothelial growth factor</subject><ispartof>European journal of cancer (1990), 2022-08, Vol.171, p.124-132</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright Elsevier Science Ltd. Aug 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-f78bd10df34f0ddaf310ad852181e20f000c0c5e991722424b716fb91ca408393</citedby><cites>FETCH-LOGICAL-c361t-f78bd10df34f0ddaf310ad852181e20f000c0c5e991722424b716fb91ca408393</cites><orcidid>0000-0002-8449-863X ; 0000-0003-4958-381X ; 0000-0003-1924-8148 ; 0000-0002-8771-6815 ; 0000-0001-7655-1405 ; 0000-0002-9201-3217</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0959804922002684$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Graham, Jeffrey</creatorcontrib><creatorcontrib>Wells, John Connor</creatorcontrib><creatorcontrib>Dudani, Shaan</creatorcontrib><creatorcontrib>Gan, Chun L.</creatorcontrib><creatorcontrib>Donskov, Frede</creatorcontrib><creatorcontrib>Lee, Jae-lyun</creatorcontrib><creatorcontrib>Kollmannsberger, Christian K.</creatorcontrib><creatorcontrib>Meza, Luis</creatorcontrib><creatorcontrib>Beuselinck, Benoit</creatorcontrib><creatorcontrib>Hansen, Aaron</creatorcontrib><creatorcontrib>North, Scott A.</creatorcontrib><creatorcontrib>Bjarnason, Georg A.</creatorcontrib><creatorcontrib>Sayegh, Nicolas</creatorcontrib><creatorcontrib>Kanesvaran, Ravindran</creatorcontrib><creatorcontrib>Wood, Lori A.</creatorcontrib><creatorcontrib>Hotte, Sebastien J.</creatorcontrib><creatorcontrib>McKay, Rana R.</creatorcontrib><creatorcontrib>Choueiri, Toni K.</creatorcontrib><creatorcontrib>Heng, Daniel Y.C.</creatorcontrib><title>Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy</title><title>European journal of cancer (1990)</title><description>Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited.
We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan–Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates.
We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42–0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36–0.71, p < 0.0001) for ICI versus mTOR.
In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.
•Non-clear cell RCC refers to a group of diverse kidney cancer subtypes.•Evidence for immune checkpoint inhibitor (ICI) use in nccRCC is limited.•Based on this retrospective study, first-line ICI therapy has activity in nccRCC.•The benefit was driven primarily by the papillary RCC subgroup.•Our results should be confirmed in prospective trials in variant histology RCC.</description><subject>Clear cell-type renal cell carcinoma</subject><subject>Clinical trials</subject><subject>Growth factors</subject><subject>Hazard identification</subject><subject>Immune checkpoint inhibitor</subject><subject>Immune checkpoint inhibitors</subject><subject>Immunotherapy</subject><subject>Inhibitors</subject><subject>Kidney cancer</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Non-clear cell RCC</subject><subject>Patients</subject><subject>Rapamycin</subject><subject>Renal cell carcinoma</subject><subject>Statistical models</subject><subject>Therapy</subject><subject>TOR protein</subject><subject>Variant histology RCC</subject><subject>Vascular endothelial growth factor</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kTFP3TAUhS1UJF6BP8BkiaVLwrWTvNhSlwoVqITE0s6Wn3Ot55DYqe1QsfLL8evr1IHpeviOpe8cQq4Y1AzY9mascTS65sB5DV0NwE_IholeViA6_olsQHayEtDKM_I5pREAetHChrw9rdmEGRMNli46O_Q50T8u76keXrQ3OFAffGUm1JEanCYa0evp-DQ6GufDrGmOqHNh_yatiylXk_NI3Tyv5Zg9muclOJ-p83u3czlEmvcY9fJ6QU6tnhJe_rvn5Nfd95-3D9Xj0_2P22-PlWm2LFe2F7uBwWCb1sIwaNsw0EOxY4IhB1uUDJgOpWQ95y1vdz3b2p1kRrcgGtmcky_Hf5cYfq-YsppdOmhoj2FNim970bedFKKg1_-hY1hj0S5UD01Xem7aQvEjZWJIKaJVS3Szjq-KgTrMokZ1mEUdZlHQqTJLCX09hrCovjiMKplSeunZRTRZDcF9FH8Htp6XbA</recordid><startdate>202208</startdate><enddate>202208</enddate><creator>Graham, Jeffrey</creator><creator>Wells, John Connor</creator><creator>Dudani, Shaan</creator><creator>Gan, Chun L.</creator><creator>Donskov, Frede</creator><creator>Lee, Jae-lyun</creator><creator>Kollmannsberger, Christian K.</creator><creator>Meza, Luis</creator><creator>Beuselinck, Benoit</creator><creator>Hansen, Aaron</creator><creator>North, Scott A.</creator><creator>Bjarnason, Georg A.</creator><creator>Sayegh, Nicolas</creator><creator>Kanesvaran, Ravindran</creator><creator>Wood, Lori A.</creator><creator>Hotte, Sebastien J.</creator><creator>McKay, Rana R.</creator><creator>Choueiri, Toni K.</creator><creator>Heng, Daniel Y.C.</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8449-863X</orcidid><orcidid>https://orcid.org/0000-0003-4958-381X</orcidid><orcidid>https://orcid.org/0000-0003-1924-8148</orcidid><orcidid>https://orcid.org/0000-0002-8771-6815</orcidid><orcidid>https://orcid.org/0000-0001-7655-1405</orcidid><orcidid>https://orcid.org/0000-0002-9201-3217</orcidid></search><sort><creationdate>202208</creationdate><title>Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy</title><author>Graham, Jeffrey ; Wells, John Connor ; Dudani, Shaan ; Gan, Chun L. ; Donskov, Frede ; Lee, Jae-lyun ; Kollmannsberger, Christian K. ; Meza, Luis ; Beuselinck, Benoit ; Hansen, Aaron ; North, Scott A. ; Bjarnason, Georg A. ; Sayegh, Nicolas ; Kanesvaran, Ravindran ; Wood, Lori A. ; Hotte, Sebastien J. ; McKay, Rana R. ; Choueiri, Toni K. ; Heng, Daniel Y.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-f78bd10df34f0ddaf310ad852181e20f000c0c5e991722424b716fb91ca408393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Clear cell-type renal cell carcinoma</topic><topic>Clinical trials</topic><topic>Growth factors</topic><topic>Hazard identification</topic><topic>Immune checkpoint inhibitor</topic><topic>Immune checkpoint inhibitors</topic><topic>Immunotherapy</topic><topic>Inhibitors</topic><topic>Kidney cancer</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Non-clear cell RCC</topic><topic>Patients</topic><topic>Rapamycin</topic><topic>Renal cell carcinoma</topic><topic>Statistical models</topic><topic>Therapy</topic><topic>TOR protein</topic><topic>Variant histology RCC</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graham, Jeffrey</creatorcontrib><creatorcontrib>Wells, John Connor</creatorcontrib><creatorcontrib>Dudani, Shaan</creatorcontrib><creatorcontrib>Gan, Chun L.</creatorcontrib><creatorcontrib>Donskov, Frede</creatorcontrib><creatorcontrib>Lee, Jae-lyun</creatorcontrib><creatorcontrib>Kollmannsberger, Christian K.</creatorcontrib><creatorcontrib>Meza, Luis</creatorcontrib><creatorcontrib>Beuselinck, Benoit</creatorcontrib><creatorcontrib>Hansen, Aaron</creatorcontrib><creatorcontrib>North, Scott A.</creatorcontrib><creatorcontrib>Bjarnason, Georg A.</creatorcontrib><creatorcontrib>Sayegh, Nicolas</creatorcontrib><creatorcontrib>Kanesvaran, Ravindran</creatorcontrib><creatorcontrib>Wood, Lori A.</creatorcontrib><creatorcontrib>Hotte, Sebastien J.</creatorcontrib><creatorcontrib>McKay, Rana R.</creatorcontrib><creatorcontrib>Choueiri, Toni K.</creatorcontrib><creatorcontrib>Heng, Daniel Y.C.</creatorcontrib><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graham, Jeffrey</au><au>Wells, John Connor</au><au>Dudani, Shaan</au><au>Gan, Chun L.</au><au>Donskov, Frede</au><au>Lee, Jae-lyun</au><au>Kollmannsberger, Christian K.</au><au>Meza, Luis</au><au>Beuselinck, Benoit</au><au>Hansen, Aaron</au><au>North, Scott A.</au><au>Bjarnason, Georg A.</au><au>Sayegh, Nicolas</au><au>Kanesvaran, Ravindran</au><au>Wood, Lori A.</au><au>Hotte, Sebastien J.</au><au>McKay, Rana R.</au><au>Choueiri, Toni K.</au><au>Heng, Daniel Y.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy</atitle><jtitle>European journal of cancer (1990)</jtitle><date>2022-08</date><risdate>2022</risdate><volume>171</volume><spage>124</spage><epage>132</epage><pages>124-132</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited.
We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan–Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates.
We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42–0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36–0.71, p < 0.0001) for ICI versus mTOR.
In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.
•Non-clear cell RCC refers to a group of diverse kidney cancer subtypes.•Evidence for immune checkpoint inhibitor (ICI) use in nccRCC is limited.•Based on this retrospective study, first-line ICI therapy has activity in nccRCC.•The benefit was driven primarily by the papillary RCC subgroup.•Our results should be confirmed in prospective trials in variant histology RCC.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><doi>10.1016/j.ejca.2022.05.002</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8449-863X</orcidid><orcidid>https://orcid.org/0000-0003-4958-381X</orcidid><orcidid>https://orcid.org/0000-0003-1924-8148</orcidid><orcidid>https://orcid.org/0000-0002-8771-6815</orcidid><orcidid>https://orcid.org/0000-0001-7655-1405</orcidid><orcidid>https://orcid.org/0000-0002-9201-3217</orcidid></addata></record> |
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| ispartof | European journal of cancer (1990), 2022-08, Vol.171, p.124-132 |
| issn | 0959-8049 1879-0852 |
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| source | Elsevier ScienceDirect Journals |
| subjects | Clear cell-type renal cell carcinoma Clinical trials Growth factors Hazard identification Immune checkpoint inhibitor Immune checkpoint inhibitors Immunotherapy Inhibitors Kidney cancer Metastases Metastasis Non-clear cell RCC Patients Rapamycin Renal cell carcinoma Statistical models Therapy TOR protein Variant histology RCC Vascular endothelial growth factor |
| title | Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy |
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