Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study
BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be conti...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-02-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1307635/full |
| _version_ | 1827353291367907328 |
|---|---|
| author | Veronica Murianni Alessio Signori Sebastiano Buti Sebastiano Buti Sara Elena Rebuzzi Sara Elena Rebuzzi Davide Bimbatti Ugo De Giorgi Silvia Chiellino Luca Galli Paolo Andrea Zucali Cristina Masini Emanuele Naglieri Giuseppe Procopio Michele Milella Lucia Fratino Cinzia Baldessari Riccardo Ricotta Veronica Mollica Mariella Sorarù Marianna Tudini Veronica Prati Andrea Malgeri Francesco Atzori Marilena Di Napoli Orazio Caffo Massimiliano Spada Franco Morelli Giuseppe Prati Franco Nolè Francesca Vignani Alessia Cavo Helga Lipari Giandomenico Roviello Fabio Catalano Alessandra Damassi Malvina Cremante Pasquale Rescigno Pasquale Rescigno Giuseppe Fornarini Giuseppe Luigi Banna Giuseppe Luigi Banna |
| author_facet | Veronica Murianni Alessio Signori Sebastiano Buti Sebastiano Buti Sara Elena Rebuzzi Sara Elena Rebuzzi Davide Bimbatti Ugo De Giorgi Silvia Chiellino Luca Galli Paolo Andrea Zucali Cristina Masini Emanuele Naglieri Giuseppe Procopio Michele Milella Lucia Fratino Cinzia Baldessari Riccardo Ricotta Veronica Mollica Mariella Sorarù Marianna Tudini Veronica Prati Andrea Malgeri Francesco Atzori Marilena Di Napoli Orazio Caffo Massimiliano Spada Franco Morelli Giuseppe Prati Franco Nolè Francesca Vignani Alessia Cavo Helga Lipari Giandomenico Roviello Fabio Catalano Alessandra Damassi Malvina Cremante Pasquale Rescigno Pasquale Rescigno Giuseppe Fornarini Giuseppe Luigi Banna Giuseppe Luigi Banna |
| author_sort | Veronica Murianni |
| collection | DOAJ |
| description | BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS. |
| first_indexed | 2024-03-08T03:23:06Z |
| format | Article |
| id | doaj.art-00c6e5c2760c42988d637261a6a49e07 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-08T03:23:06Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-00c6e5c2760c42988d637261a6a49e072024-02-12T04:45:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-02-011410.3389/fonc.2024.13076351307635Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 studyVeronica Murianni0Alessio Signori1Sebastiano Buti2Sebastiano Buti3Sara Elena Rebuzzi4Sara Elena Rebuzzi5Davide Bimbatti6Ugo De Giorgi7Silvia Chiellino8Luca Galli9Paolo Andrea Zucali10Cristina Masini11Emanuele Naglieri12Giuseppe Procopio13Michele Milella14Lucia Fratino15Cinzia Baldessari16Riccardo Ricotta17Veronica Mollica18Mariella Sorarù19Marianna Tudini20Veronica Prati21Andrea Malgeri22Francesco Atzori23Marilena Di Napoli24Orazio Caffo25Massimiliano Spada26Franco Morelli27Giuseppe Prati28Franco Nolè29Francesca Vignani30Alessia Cavo31Helga Lipari32Giandomenico Roviello33Fabio Catalano34Alessandra Damassi35Malvina Cremante36Pasquale Rescigno37Pasquale Rescigno38Giuseppe Fornarini39Giuseppe Luigi Banna40Giuseppe Luigi Banna41Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, Genoa, ItalyMedical Oncology Unit, University Hospital of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyMedical Oncology Unit, Ospedale San Paolo, Savona, ItalyDepartment of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, ItalyOncologia 1, Istituto Oncologico Veneto, IOV - IRCCS, Padova, ItalyMedical Oncology Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyMedical Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy0Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy1Department of Oncology, IRCCS, Humanitas Clinical and Research Center, Department of Biochemical Sciences, Humanitas University, Milano, Italy2Medical Oncology, AUSL – IRCCS di Reggio Emilia, Reggio Emilia, Italy3U.O. Oncologia, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy4Medical Oncology, Fondazione IRCCS – Istituto Nazionale dei Tumori, Milano, Italy5Department of Medical Oncology, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy6Department of Medical Oncology, CRO Aviano – Centro di Riferimento Oncologico IRCCS, Aviano, Italy7Department of Oncology and Hematology – Oncology Unit, Azienda Ospedaliera Universitaria di Modena, Modena, Italy8Oncology Unit, IRCCS MultiMedica, Sesto San Giovanni, Milano, Italy9Medical Oncology, IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy0U.O.C. Medical Oncology, Ospedale Camposampiero, Padova, Italy1Medical Oncology, Osp. San Salvatore, ASL1 Avezzano Sulmona, L’Aquila, Italy2Oncology Unit, Ospedale Michele e Pietro Ferrero, Verduno, Italy3Medical Oncology Unit, Policlinico Universitario Campus Bio Medico, Roma, Italy4Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy5Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy6Medical Oncology, Ospedale S. Chiara, Trento, Italy7UOC Oncology, Fondazione Istituto San Raffaele Giglio di Cefalù, Cefalù, Italy8Medical Oncology Department, Casa Sollievo Della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy9Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Reggio Emilia, Italy0Medical Oncology Division of Urogenital & Head & Neck Tumors, IEO, European Institute of Oncology IRCCS, Milano, Italy1Division of Medical Oncology, Ordine Mauriziano Hospital, Torino, Italy2Oncology Unit, Villa Scassi Hospital, Genoa, Italy3Medical Oncology, Azienda Ospedaliera per l’Emergenza Cannizzaro, Catania, Italy4Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Firenze, Firenze, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy5Translationsal and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom6Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy7Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom8Faculty of Science and Health, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United KingdomBackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.https://www.frontiersin.org/articles/10.3389/fonc.2024.1307635/fullmetastatic renal cell carcinomaimmunotherapyimmune checkpoint inhibitorsnivolumabtreatment beyond progressiontime to strategy failure |
| spellingShingle | Veronica Murianni Alessio Signori Sebastiano Buti Sebastiano Buti Sara Elena Rebuzzi Sara Elena Rebuzzi Davide Bimbatti Ugo De Giorgi Silvia Chiellino Luca Galli Paolo Andrea Zucali Cristina Masini Emanuele Naglieri Giuseppe Procopio Michele Milella Lucia Fratino Cinzia Baldessari Riccardo Ricotta Veronica Mollica Mariella Sorarù Marianna Tudini Veronica Prati Andrea Malgeri Francesco Atzori Marilena Di Napoli Orazio Caffo Massimiliano Spada Franco Morelli Giuseppe Prati Franco Nolè Francesca Vignani Alessia Cavo Helga Lipari Giandomenico Roviello Fabio Catalano Alessandra Damassi Malvina Cremante Pasquale Rescigno Pasquale Rescigno Giuseppe Fornarini Giuseppe Luigi Banna Giuseppe Luigi Banna Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study Frontiers in Oncology metastatic renal cell carcinoma immunotherapy immune checkpoint inhibitors nivolumab treatment beyond progression time to strategy failure |
| title | Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study |
| title_full | Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study |
| title_fullStr | Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study |
| title_full_unstemmed | Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study |
| title_short | Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study |
| title_sort | time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab post hoc analysis of the meet uro 15 study |
| topic | metastatic renal cell carcinoma immunotherapy immune checkpoint inhibitors nivolumab treatment beyond progression time to strategy failure |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1307635/full |
| work_keys_str_mv | AT veronicamurianni timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT alessiosignori timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT sebastianobuti timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT sebastianobuti timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT saraelenarebuzzi timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT saraelenarebuzzi timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT davidebimbatti timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT ugodegiorgi timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT silviachiellino timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT lucagalli timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT paoloandreazucali timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT cristinamasini timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT emanuelenaglieri timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT giuseppeprocopio timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT michelemilella timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT luciafratino timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT cinziabaldessari timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT riccardoricotta timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT veronicamollica timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT mariellasoraru timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT mariannatudini timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT veronicaprati timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT andreamalgeri timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT francescoatzori timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT marilenadinapoli timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT oraziocaffo timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT massimilianospada timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT francomorelli timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT giuseppeprati timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT franconole timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT francescavignani timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT alessiacavo timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT helgalipari timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT giandomenicoroviello timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT fabiocatalano timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT alessandradamassi timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT malvinacremante timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT pasqualerescigno timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT pasqualerescigno timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT giuseppefornarini timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT giuseppeluigibanna timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study AT giuseppeluigibanna timetostrategyfailureandtreatmentbeyondprogressioninpretreatedmetastaticrenalcellcarcinomapatientsreceivingnivolumabposthocanalysisofthemeeturo15study |