Roberto Iacovelli1, Chiara Ciccarese2, Emilio Bria3, Davide Bimbatti2, Emanuela Fantinel2, Claudia Mosillo4, Iolanda Bisogno2, Matteo Brunelli5, Giampaolo Tortora6, Camillo Porta7. 1. Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Italy; Oncology Unit, Università Cattolica del Sacro Cuore, Fondazione Policlinico "A. Gemelli", Rome, Italy. Electronic address: roberto.iacovelli@aovr.veneto.it. 2. Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Italy. 3. Oncology Unit, Università Cattolica del Sacro Cuore, Fondazione Policlinico "A. Gemelli", Rome, Italy. 4. Department of Radiology, Oncology and Human Pathology, Oncology Unit, Sapienza University of Rome, Rome, Italy. 5. Department of Diagnostics and Public Health, University of Verona, Verona, Italy. 6. Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Italy; Oncology Unit, Università Cattolica del Sacro Cuore, Fondazione Policlinico "A. Gemelli", Rome, Italy. 7. Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy.
Abstract
BACKGROUND: Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS. We performed a meta-analysis of randomized trials comparing immunotherapy to standard of care (SOC) in mRCC. METHODS: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. Data extraction was conducted according to the PRISMA statement. The measured outcomes were OS, PFS, and ORR. RESULTS: A total of 2832 patients were available for evaluation of OS, and 3033 for PFS and ORR. Compared to SOC, immunotherapy improved OS (HR = 0.75; 95%CI 0.66-0.85; p < 0.001), and PFS (HR = 0.88; 95%CI 0.80-0.97; p = 0.009). The PFS benefit was not confirmed when considering patients treated in first-line only (p = 0.10). Conversely, significant ORR improvement was found in patients treated in first-line only (HR = 1.14; 95%CI 1.02-1.28; p = 0.03) but not in the overall population. CONCLUSIONS: Immunotherapy improved OS compared to SOC in mRCC, irrespective of treatment line. In first-line, immunotherapy also increased the ORR compared to sunitinib. A lack of correlation between OS and PFS was confirmed, the latter to be used cautiously for the design and interpretation of trials involving immunotherapy in mRCC.
BACKGROUND: Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS. We performed a meta-analysis of randomized trials comparing immunotherapy to standard of care (SOC) in mRCC. METHODS: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. Data extraction was conducted according to the PRISMA statement. The measured outcomes were OS, PFS, and ORR. RESULTS: A total of 2832 patients were available for evaluation of OS, and 3033 for PFS and ORR. Compared to SOC, immunotherapy improved OS (HR = 0.75; 95%CI 0.66-0.85; p < 0.001), and PFS (HR = 0.88; 95%CI 0.80-0.97; p = 0.009). The PFS benefit was not confirmed when considering patients treated in first-line only (p = 0.10). Conversely, significant ORR improvement was found in patients treated in first-line only (HR = 1.14; 95%CI 1.02-1.28; p = 0.03) but not in the overall population. CONCLUSIONS: Immunotherapy improved OS compared to SOC in mRCC, irrespective of treatment line. In first-line, immunotherapy also increased the ORR compared to sunitinib. A lack of correlation between OS and PFS was confirmed, the latter to be used cautiously for the design and interpretation of trials involving immunotherapy in mRCC.