TY - JOUR
T1 - Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors
AU - Graham, Jeffrey
AU - Shah, Amishi Y.
AU - Wells, J. Connor
AU - McKay, Rana R.
AU - Vaishampayan, Ulka
AU - Hansen, Aaron
AU - Donskov, Frede
AU - Bjarnason, Georg A.
AU - Beuselinck, Benoit
AU - De Velasco, Guillermo
AU - Iafolla, Marco
AU - Duh, Mei S.
AU - Huynh, Lynn
AU - Chang, Rose
AU - Zanotti, Giovanni
AU - Ramaswamy, Krishnan
AU - Choueiri, Toni K.
AU - Tannir, Nizar M.
AU - Heng, Daniel Y.C.
N1 - Publisher Copyright:
Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - BACKGROUND: Immuno-oncology (IO) therapies have changed the treatment standards of metastatic renal cell carcinoma (mRCC). However, the effectiveness of targeted therapy following discontinuation of IO therapy in real-world settings has not been well studied. OBJECTIVE: To describe treatment sequence and assess clinical effectiveness of targeted therapy for mRCC patients who received prior IO therapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal cohort study using data from eight international cancer centers was conducted. Patients with mRCC were ≥18yr old, received IO therapy in any line, and initiated targeted therapy following IO therapy discontinuation. INTERVENTION: Patients were treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or mammalian target of rapamycin inhibitors (mTORIs). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were time to treatment discontinuation (TTD), overall survival (OS), and objective response rate (ORR). Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Models were adjusted for age, sex, therapy line, and International Metastatic RCC Database Consortium risk group. RESULTS AND LIMITATIONS: Among 314 patients, 276 (87.9%) and 38 (12.1%) were treated with VEGFR-TKI and mTORI therapy, respectively. The most common tyrosine kinase inhibitor treatments were axitinib, cabozantinib, and sunitinib following IO therapy. In adjusted models, patients treated with VEGFR-TKI versus mTORI therapy had lower hazard of TTD after IO treatment (aHR=0.46; 95% CI: 0.30-0.71; p < 0.01). One-year OS probability (65% vs 47%, p < 0.01) and proportion of ORR (29.8% vs 3.6%, p < 0.01) were significantly greater for patients treated with VEGFR-TKIs versus those treated with mTORIs. CONCLUSIONS: Targeted therapy has clinical activity following IO treatment. Patients who received VEGFR-TKIs versus mTORIs following IO therapy had improved clinical outcomes. These findings may help inform treatment guidelines and clinical practice for patients post-IO therapy. PATIENT SUMMARY: Patients may continue to experience clinical benefits from targeted therapies after progression on immuno-oncology treatment.
AB - BACKGROUND: Immuno-oncology (IO) therapies have changed the treatment standards of metastatic renal cell carcinoma (mRCC). However, the effectiveness of targeted therapy following discontinuation of IO therapy in real-world settings has not been well studied. OBJECTIVE: To describe treatment sequence and assess clinical effectiveness of targeted therapy for mRCC patients who received prior IO therapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal cohort study using data from eight international cancer centers was conducted. Patients with mRCC were ≥18yr old, received IO therapy in any line, and initiated targeted therapy following IO therapy discontinuation. INTERVENTION: Patients were treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or mammalian target of rapamycin inhibitors (mTORIs). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were time to treatment discontinuation (TTD), overall survival (OS), and objective response rate (ORR). Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Models were adjusted for age, sex, therapy line, and International Metastatic RCC Database Consortium risk group. RESULTS AND LIMITATIONS: Among 314 patients, 276 (87.9%) and 38 (12.1%) were treated with VEGFR-TKI and mTORI therapy, respectively. The most common tyrosine kinase inhibitor treatments were axitinib, cabozantinib, and sunitinib following IO therapy. In adjusted models, patients treated with VEGFR-TKI versus mTORI therapy had lower hazard of TTD after IO treatment (aHR=0.46; 95% CI: 0.30-0.71; p < 0.01). One-year OS probability (65% vs 47%, p < 0.01) and proportion of ORR (29.8% vs 3.6%, p < 0.01) were significantly greater for patients treated with VEGFR-TKIs versus those treated with mTORIs. CONCLUSIONS: Targeted therapy has clinical activity following IO treatment. Patients who received VEGFR-TKIs versus mTORIs following IO therapy had improved clinical outcomes. These findings may help inform treatment guidelines and clinical practice for patients post-IO therapy. PATIENT SUMMARY: Patients may continue to experience clinical benefits from targeted therapies after progression on immuno-oncology treatment.
KW - Immuno-oncology
KW - Mammalian target of rapamycin inhibitors
KW - Metastatic renal cell carcinoma
KW - Real-world effectiveness
KW - Sequential therapies
KW - Targeted therapy
KW - Vascular endothelial growth factor receptor tyrosine kinase inhibitors
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U2 - 10.1016/j.euo.2019.11.001
DO - 10.1016/j.euo.2019.11.001
M3 - Article
C2 - 31786162
AN - SCOPUS:85102090639
SN - 2588-9311
VL - 4
SP - 102
EP - 111
JO - European Urology Oncology
JF - European Urology Oncology
IS - 1
ER -