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1. Enfortumab Vedotin Following Platinum Chemotherapy and Avelumab Maintenance in Patients with Metastatic Urothelial Carcinoma: A Retrospective Data from the ARON-2EV Study

Author

Fiala, Ondřej, Massari, Francesco, Basso, Umberto, Giannatempo, Patrizia, Grande, Enrique, Buti, Sebastiano, Myint, Zin W., De Giorgi, Ugo, Pichler, Renate, Grillone, Francesco, Ürün, Yüksel, Calabrò, Fabio, Bourlon, Maria T., Galli, Luca, Kanesvaran, Ravindran, Roviello, Giandomenico, Kucharz, Jakub, Rizzo, Mimma, Park, Se Hoon, Cerbone, Linda, Seront, Emmanuel, Messina, Carlo, Molina-Cerrillo, Javier, Santini, Daniele, Yano, Akihiro, Incorvaia, Lorena, Catalano, Martina, Pinto, Alvaro, Formisano, Luigi, Soares, Andrey, Facchini, Gaetano, Fornarini, Giuseppe, Poprach, Alexandr, Rebuzzi, Sara Elena, Nasso, Cecilia, Spinelli, Gian Paolo, Angel, Martin, Stellato, Marco, Tural, Deniz, Aurilio, Gaetano, Epstein, Ilana, Carrozza, Francesco, Monteiro, Fernando Sabino Marques, Benedetti, Giovanni, Büchler, Tomáš, Ortega, Cinzia, Zakopoulou, Roubini, Battelli, Nicola, Porta, Camillo, Bellmunt, Joaquin, Gupta, Shilpa, and Santoni, Matteo

Published
2024
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2. Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study

Author

Rizzo, Mimma, Soares, Andrey, Grande, Enrique, Bamias, Aristotelis, Kopp, Ray Manneh, Lenci, Edoardo, Buttner, Thomas, Salah, Samer, Grillone, Francesco, de Carvalho, Icaro Thiago, Tapia, Jose Carlos, Gucciardino, Calogero, Pinto, Alvaro, Mennitto, Alessia, Abahssain, Halima, Rescigno, Pasquale, Myint, Zin, Takeshita, Hideki, Spinelli, Gian Paolo, Popovic, Lazar, Vitale, Maria Giuseppa, Fiala, Ondrej, Giannatempo, Patrizia, Zakopoulou, Roubini, Carrozza, Francesco, Massari, Francesco, Monteiro, Fernando Sabino Marques, Pace, Maria Paola, Giannini, Massimo, Roviello, Giandomenico, Porta, Camillo, Battelli, Nicola, Kanesvaran, Ravindran, and Santoni, Matteo

Published
2024
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3. Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy (PBC) in Patients With Advanced Urothelial Carcinoma (aUC): Real World Experience.

Author

Bakaloudi, Dimitra, Talukder, Rafee, Lin, Genevieve, Makrakis, Dimitrios, Diamantopoulos, Leonidas, Tripathi, Nishita, Agarwal, Neeraj, Zakopoulou, Roubini, Bamias, Aristotelis, Brown, Jason, Pinato, David, Korolewicz, James, Jindal, Tanya, Koshkin, Vadim, Murgić, Jure, Miletić, Marija, Frobe, Ana, Johnson, Jeffrey, Zakharia, Yousef, Drakaki, Alexandra, Rodriguez-Vida, Alejo, Rey-Cárdenas, Macarena, Castellano, Daniel, Buznego, Lucia, Duran, Ignacio, Carballeira, Clara, Barrera, Rafael, Marmorejo, David, McKay, Rana, Stewart, Tyler, Gupta, Shilpa, Ruplin, Andrew, Yu, Evan, Khaki, Ali, and Grivas, Petros

Subjects
Anti-PD(L)1, Bladder cancer, Immune Checkpoint Inhibitors, Immunotherapy, Urinary tract cancer, Humans, Antibodies, Monoclonal, Retrospective Studies, Carcinoma, Transitional Cell, Platinum, Urinary Bladder Neoplasms
Abstract

BACKGROUND: Platinum-based chemotherapy (PBC) followed by avelumab switch maintenance in nonprogressors is standard first line (1L) treatment for advanced urothelial carcinoma (aUC). We describe clinical features and outcomes in a real-world cohort treated with avelumab maintenance for aUC. MATERIALS AND METHODS: This was a retrospective cohort study of patients (pts) who received 1L switch maintenance avelumab after no progression on PBC for aUC. We calculated progression-free survival (PFS) and overall survival (OS) from initiation of maintenance avelumab. We also described OS and PFS for specific subsets using Cox regression and observed response rate (ORR). RESULTS: A total of 108 pts with aUC from 14 sites treated with maintenance avelumab were included. There was a median of 6 weeks1-30 from end of PBC to avelumab initiation; median follow-up time from avelumab initiation was 8.8 months (1-42.7). Median [m]PFS was 9.6 months (95%CI 7.5-12.1) and estimated 1-year OS was 72.5%. CR/PR (vs. SD) to 1L PBC (HR = 0.33, 95% CI 0.13-0.87) and ECOG PS 0 (vs. ≥1), (HR = 0.15, 95% CI 0.05-0.47) were associated with longer OS. The presence of liver metastases was associated with shorter PFS (HR = 2.32, 95% CI 1.17-4.59). ORR with avelumab maintenance was 28.7% (complete response 17.6%, partial response 11.1%), 29.6% stable disease, 26.9% progressive disease as best response (14.8% best response unknown). CONCLUSIONS: Results seem relatively consistent with findings from JAVELIN Bladder100 trial and recent real world studies. Prior response to platinum-based chemotherapy, ECOG PS 0, and absence of liver metastases were favorable prognostic factors. Limitations include the retrospective design, lack of randomization and central scan review, and possible selection/confounding biases.

Published
2023

4. Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma

Author

Talukder, Rafee, Makrakis, Dimitrios, Lin, Genevieve Ihsiu, Diamantopoulos, Leonidas N, Dawsey, Scott, Gupta, Shilpa, Carril-Ajuria, Lucia, Castellano, Daniel, de Kouchkovsky, Ivan, Jindal, Tanya, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Tripathi, Nishita, Agarwal, Neeraj, Vather-Wu, Naomi, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Cortellini, Alessio, Fulgenzi, Claudia Angela Maria, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Gupta, Kavita, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Lu, Eric, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Wright, Jonathan L, Yu, Evan Y, Montgomery, Robert Bruce, Hsieh, Andrew C, Grivas, Petros, and Khaki, Ali Raza

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Precision Medicine, Cancer, Immunotherapy, 6.1 Pharmaceuticals, Humans, Immune Checkpoint Inhibitors, Carcinoma, Transitional Cell, Retrospective Studies, Cohort Studies, Treatment Outcome, Urinary Bladder Neoplasms, Bladder cancer, Platinum resistance, Checkpoint Inhibitor, Outcomes, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundEarly progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.Patients and methodsWe performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.ResultsWe included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.ConclusionAmong patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.

Published
2022

5. Association of prior local therapy and outcomes with programmed‐death ligand‐1 inhibitors in advanced urothelial cancer

Author

Makrakis, Dimitrios, Talukder, Rafee, Diamantopoulos, Leonidas N, Carril-Ajuria, Lucia, Castellano, Daniel, De Kouchkovsky, Ivan, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Santos, Victor S, Agarwal, Neeraj, Jain, Jayanshu, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Grant, Michael, Lythgoe, Mark P, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Shreck, Evan, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Kumar, Vivek, Di Lorenzo, Giuseppe, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Yu, Evan Y, Wright, Jonathan L, Grivas, Petros, and Khaki, Ali Raza

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Radiation Oncology, 6.1 Pharmaceuticals, Good Health and Well Being, Humans, Immune Checkpoint Inhibitors, Retrospective Studies, Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, bladder cancer, urinary tract neoplasms, urothelial carcinoma, immune checkpoint inhibitors, immunotherapy, outcomes, #uroonc, #utuc, #BladderCancer, #blcsm, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis
Abstract

ObjectivesTo compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease.Patients and methodsWe performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan-Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors.ResultsWe included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately.ConclusionPrior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study's retrospective nature, lack of randomization, and possible selection and confounding biases.

Published
2022

6. Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study

Author

Santoni, Matteo, Massari, Francesco, Takeshita, Hideki, Tapia, Jose Carlos, Dionese, Michele, Pichler, Renate, Rizzo, Mimma, Lam, Elaine T., Grande, Enrique, Kemp, Robert, Molina-Cerrillo, Javier, Calabrò, Fabio, Tural, Deniz, Küronya, Zsófia, Kucharz, Jakub, Fiala, Ondrej, Seront, Emmanuel, Kopp, Ray Manneh, Abahssain, Halima, Kopecky, Jindrich, Martignetti, Angelo, Kanesvaran, Ravindran, Zakopoulou, Roubini, Ansari, Jawaher, Landmesser, Johannes, Mollica, Veronica, Porta, Camillo, Bellmunt, Joaquim, Salah, Samer, and Santini, Daniele

Published
2023
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7. Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study

Author

Fiala, Ondřej, Buti, Sebastiano, Takeshita, Hideki, Okada, Yohei, Massari, Francesco, Palacios, Georgia Anguera, Dionese, Michele, Scagliarini, Sarah, Büttner, Thomas, Fornarini, Giuseppe, Myint, Zin W., Galli, Luca, Souza, Vinicius Carrera, Pichler, Renate, De Giorgi, Ugo, Quiroga, María Natalia Gandur, Gilbert, Danielle, Popovic, Lazar, Grande, Enrique, Mammone, Giulia, Berardi, Rossana, Crabb, Simon J., Molina-Cerrillo, Javier, Freitas, Marcelo, Luz, Murilo, Iacovelli, Roberto, Calabrò, Fabio, Tural, Deniz, Atzori, Francesco, Küronya, Zsófia, Chiari, Rita, Campos, Saul, Caffo, Orazio, Fay, André P., Kucharz, Jakub, Zucali, Paolo Andrea, Rinck, José Augusto, Zeppellini, Annalisa, Bastos, Diogo Assed, Aurilio, Gaetano, Mota, Augusto, Trindade, Karine, Ortega, Cinzia, Sade, Juan Pablo, Rizzo, Mimma, Vau, Nuno, Giannatempo, Patrizia, Barillas, Allan, Monteiro, Fernando Sabino Marques, Dauster, Breno, Cattrini, Carlo, Nogueira, Lucas, de Carvalho Fernandes, Roni, Seront, Emmanuel, Aceituno, Luís Garcia, Grillone, Francesco, Cutuli, Hernan Javier, Fernandez, Mauricio, Bassanelli, Maria, Roviello, Giandomenico, Abahssain, Halima, Procopio, Giuseppe, Milella, Michele, Kopecky, Jindrich, Martignetti, Angelo, Messina, Carlo, Caitano, Manuel, Inman, Eva, Kanesvaran, Ravindran, Herchenhorn, Daniel, Santini, Daniele, Manneh, Ray, Bisonni, Renato, Zakopoulou, Roubini, Mosca, Alessandra, Morelli, Franco, Maluf, Fernando, Soares, Andrey, Nunes, Fernando, Pinto, Alvaro, Zgura, Anca, Incorvaia, Lorena, Ansari, Jawaher, Zabalza, Ignacio Ortego, Landmesser, Johannes, Rizzo, Alessandro, Mollica, Veronica, Sorgentoni, Giulia, Battelli, Nicola, Porta, Camillo, Bellmunt, Joaquim, and Santoni, Matteo

Published
2023
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8. Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Author

Makrakis, Dimitrios, Talukder, Rafee, Lin, Genevieve Ihsiu, Diamantopoulos, Leonidas N, Dawsey, Scott, Gupta, Shilpa, Carril-Ajuria, Lucia, Castellano, Daniel, de Kouchkovsky, Ivan, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Tripathi, Nishita, Agarwal, Neeraj, Vather-Wu, Naomi, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Cortellini, Alessio, Fulgenzi, Claudia Angela Maria, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Gupta, Kavita, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Lu, Eric, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Jang, Albert, Barata, Pedro, Sonpavde, Guru, Yu, Evan Y, Montgomery, Robert Bruce, Grivas, Petros, and Khaki, Ali Raza

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Clinical Research, Immunotherapy, Orphan Drug, Digestive Diseases, Rare Diseases, Precision Medicine, Liver Disease, Carcinoma, Transitional Cell, Humans, Immune Checkpoint Inhibitors, Liver Neoplasms, Retrospective Studies, Urinary Bladder Neoplasms, Bladder cancer, Immune checkpoint inhibitors, Advanced urothelial carcinoma, Outcomes, Metastatic cancer, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundSites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI.MethodsWe identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line.ResultsWe identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant.ConclusionBone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

Published
2022

9. Papillary Renal Cell Carcinoma: Outcomes for Patients Receiving First-line Immune-based Combinations or Tyrosine Kinase Inhibitors from the ARON-1 Study

Author

Massari, Francesco, Mollica, Veronica, Fiala, Ondrej, De Giorgi, Ugo, Kucharz, Jakub, Vitale, Maria Giuseppa, Molina-Cerrillo, Javier, Facchini, Gaetano, Seront, Emmanuel, Lenci, Edoardo, Bourlon, Maria T., Carrozza, Francesco, Pichler, Renate, Lolli, Cristian, Myint, Zin W., Kanesvaran, Ravindran, Torniai, Mariangela, Rescigno, Pasquale, Gomez de Liaño, Alfonso, Zakopoulou, Roubini, Buti, Sebastiano, Porta, Camillo, Grande, Enrique, and Santoni, Matteo

Published
2024
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10. Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin

Author

Talukder, Rafee, Makrakis, Dimitrios, Diamantopoulos, Leonidas N, Carril-Ajuria, Lucia, Castellano, Daniel, De Kouchkovsky, Ivan, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Santos, Victor S, Agarwal, Neeraj, Jain, Jayanshu, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Grant, Michael, Lythgoe, Mark P, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Shreck, Evan, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Velho, Pedro Isaacsson, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Yu, Evan Y, Wright, Jonathan L, Grivas, Petros, and Khaki, Ali Raza

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Precision Medicine, 6.1 Pharmaceuticals, Good Health and Well Being, Adjuvants, Immunologic, Administration, Intravesical, BCG Vaccine, Carcinoma, Transitional Cell, Humans, Immune Checkpoint Inhibitors, Neoplasm Recurrence, Local, Retrospective Studies, Urinary Bladder Neoplasms, Bladder cancer, BCG, Immunotherapy, Outcomes, Urinary tract neoplasms, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundImmune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes.Patients and methodsWe performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors.ResultsA total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings.ConclusionPrior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

Published
2022

11. Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma

Author

Talukder, Rafee, Bakaloudi, Dimitra Rafailia, Makrakis, Dimitrios, Diamantopoulos, Leonidas N., Enright, Thomas, Leary, Jacob, Raychaudhuri, Ruben, Tripathi, Nishita, Agarwal, Neeraj, Jindal, Tanya, Brown, Jason R., Zakharia, Yousef, Rey-Cárdenas, Macarena, Castellano, Daniel, Nguyen, Charles B., Alva, Ajjai, Zakopoulou, Roubini, Bamias, Aristotelis, Barrera, Rafael Morales, Marmorejo, David, Drakaki, Alexandra, Pinato, David J., Korolewicz, James, Buznego, Lucia Alonso, Duran, Ignacio, Carballeira, Clara Castro, McKay, Rana R., Stewart, Tyler F., Gupta, Shilpa, Barata, Pedro, Yu, Evan Y., Koshkin, Vadim S., Khaki, Ali Raza, and Grivas, Petros

Published
2024
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12. A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

Author

Khaki, Ali Raza, Li, Ang, Diamantopoulos, Leonidas N, Miller, Natalie J, Carril-Ajuria, Lucia, Castellano, Daniel, De Kouchkovsky, Ivan, Koshkin, Vadim, Park, Joseph, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler, Santos, Victor, Agarwal, Neeraj, Jain, Jayanshu, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael, Nelson, Ariel, Hoimes, Christopher J, Shreck, Evan, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Kumar, Vivek, Lythgoe, Mark P, Pinato, David J, Murgic, Jure, Fröbe, Ana, Joshi, Monika, Isaacsson Velho, Pedro, Hahn, Noah, Alonso Buznego, Lucia, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Galsky, Matthew D, Sonpavde, Guru, Yu, Evan Y, Shankaran, Veena, Lyman, Gary H, and Grivas, Petros

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Patient Safety, Cancer, Digestive Diseases, Prevention, Liver Disease, Aged, Carcinoma, Transitional Cell, Cohort Studies, Female, Humans, Immune Checkpoint Inhibitors, Prognosis, Retrospective Studies, Urinary Bladder Neoplasms, Bladder cancer, Immunotherapy, Outcome research, Prognostic model, Urothelial carcinoma, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundWhile immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1).ObjectiveWe aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study.Design, setting, and participantsPatients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study.Outcome measurements and statistical analysisWe used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated.Results and limitationsAmong 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin 5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation.ConclusionsWe developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued.Patient summaryWith multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE  HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin 5, and liver metastases each one point, with a higher score being associated with worse overall survival.

Published
2021

13. Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Author

Makrakis, Dimitrios, Bakaloudi, Dimitra Rafailia, Talukder, Rafee, Lin, Genevieve Ihsiu, Diamantopoulos, Leonidas N., Jindal, Tanya, Vather-Wu, Naomi, Zakharia, Yousef, Tripathi, Nishita, Agarwal, Neeraj, Dawsey, Scott, Gupta, Shilpa, Lu, Eric, Drakaki, Alexandra, Liu, Sandy, Zakopoulou, Roubini, Bamias, Aristotelis, Fulgenzi, Claudia-Maria, Cortellini, Alessio, Pinato, David, Barata, Pedro, Grivas, Petros, Khaki, Ali Raza, and Koshkin, Vadim S.

Published
2023
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14. Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy

Author

Bamias, Aristotelis, Tzannis, Kimon, Dimitriadis, Ioannis, Tsironis, Georgios, Papatheorodidi, Alkistis-Maria, Tsiara, Anna, Fragkoulis, Charalampos, Xirokosta, Aikaterini, Barbarousi, Despoina, Papadopoulos, Georgios, Zakopoulou, Roubini, Varkarakis, Ioannis, Mitsogiannis, Iraklis, Adamakis, Ioannis, Alamanis, Christos, Stravodimos, Konstantinos, Papatsoris, Athanasios G., Dellis, Athanasios E., Drivalos, Alexandros, Ntoumas, Konstantinos, Matsouka, Haris, Halvatsiotis, Panayiotis, Raptis, Athanasios, Gerotziafas, Grigorios T., and Dimopoulos, Meletios Athanasios

Published
2020
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15. Lymphocytic infiltration and Chemotherapy Response Score as prognostic markers in ovarian cancer patients treated with Neoadjuvant chemotherapy

Author

Liontos, Michalis, Sotiropoulou, Maria, Kaparelou, Maria, Tzannis, Kimon, Tsironis, George, Kyriazoglou, Anastasios, Tsiara, Anna, Zakopoulou, Roubini, Koutsoukos, Konstantinos, Zagouri, Flora, Thomakos, Nikolaos, Haidopoulos, Dimitrios, Rodolakis, Alexandros, Dimopoulos, Meletios A., and Bamias, Aristotelis

Published
2020
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16. Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Oncology Combinations (ARON-1)

Author

Santoni, Matteo, Massari, Francesco, Myint, Zin W., Iacovelli, Roberto, Pichler, Martin, Basso, Umberto, Kopecky, Jindrich, Kucharz, Jakub, Buti, Sebastiano, Salfi, Alessia, Büttner, Thomas, De Giorgi, Ugo, Kanesvaran, Ravindran, Fiala, Ondřej, Grande, Enrique, Zucali, Paolo Andrea, Fornarini, Giuseppe, Bourlon, Maria T, Scagliarini, Sarah, Molina-Cerrillo, Javier, Aurilio, Gaetano, Matrana, Marc R, Pichler, Renate, Cattrini, Carlo, Büchler, Tomas, Seront, Emmanuel, Calabrò, Fabio, Pinto, Alvaro, Berardi, Rossana, Zgura, Anca, Mammone, Giulia, Ansari, Jawaher, Atzori, Francesco, Chiari, Rita, Zakopoulou, Roubini, Caffo, Orazio, Procopio, Giuseppe, Bassanelli, Maria, Zampiva, Ilaria, Messina, Carlo, Küronya, Zsófia, Mosca, Alessandra, Bhuva, Dipen, Vau, Nuno, Incorvaia, Lorena, Rebuzzi, Sara Elena, Roviello, Giandomenico, Zabalza, Ignacio Ortego, Rizzo, Alessandro, Mollica, Veronica, Catalini, Ilaria, Monteiro, Fernando Sabino M., Montironi, Rodolfo, Battelli, Nicola, Rizzo, Mimma, and Porta, Camillo

Published
2023
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18. Inflammation and Immunity Gene Expression Patterns and Machine Learning Approaches in Association with Response to Immune-Checkpoint Inhibitors-Based Treatments in Clear-Cell Renal Carcinoma

Author

Dovrolis, Nikolas, primary, Katifelis, Hector, additional, Grammatikaki, Stamatiki, additional, Zakopoulou, Roubini, additional, Bamias, Aristotelis, additional, Karamouzis, Michalis V., additional, Souliotis, Kyriakos, additional, and Gazouli, Maria, additional

Published
2023
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19. Clinical and biological implications of Hippo pathway dysregulation in sarcomas

Author

Kyriazoglou Anastasios, Zakopoulou Roubini, Zagouri Flora, Bamias Aristotelis, and Dimopoulos Meletios Athanasios

Subjects
sarcomas, hippo pathway, yap, taz, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Sarcomas are mesenchymal malignant tumors with poor prognosis and limited treatment options. Hippo pathway is a recently discovered pathway normally involved in organ development and wound healing. Hippo signaling is often altered in solid tumors. The molecular elements of Hippo signaling include MST1/2 and LATS1/2 kinases which phosphorylate and regulate the activity of YAP and TAZ co-transcriptional activators. Hippo pathway cross-talks with several molecular pathways with known oncogenic function. In sarcomas Hippo signaling plays a pivotal role in tumorigenesis, evolution and resistance in chemotherapy regimens. Targeting Hippo pathway could potentially improve prognosis and outcome of sarcoma patients.

Published
2019
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21. Geographical differences in the management of metastatic de novo renal cell carcinoma in the era of immune-combinations

Author

PORTA, Camillo, primary, BAMIAS, Aristotelis, additional, ZAKOPOULOU, Roubini, additional, MYINT, Zin W., additional, CAVASIN, Nicolò, additional, IACOVELLI, Roberto, additional, PICHLER, Martin, additional, KOPECKY, Jindrich, additional, KUCHARZ, Jakub, additional, RIZZO, Mimma, additional, GALLI, Luca, additional, BÜTTNER, Thomas, additional, DE GIORGI, Ugo, additional, KANESVARAN, Ravindran, additional, FIALA, Ondřej, additional, GRANDE, Enrique, additional, ZUCALI, Paolo A., additional, KOPP, Ray M., additional, FORNARINI, Giuseppe, additional, BOURLON, Maria T., additional, SCAGLIARINI, Sarah, additional, MOLINA-CERRILLO, Javier, additional, AURILIO, Gaetano, additional, MATRANA, Marc R., additional, PICHLER, Renate, additional, CATTRINI, Carlo, additional, BÜCHLER, Tomáš, additional, MASSARI, Francesco, additional, MOLLICA, Veronica, additional, SERONT, Emmanuel, additional, CALABRÒ, Fabio, additional, PINTO, Alvaro, additional, BERARDI, Rossana, additional, ZGURA, Anca, additional, MAMMONE, Giulia, additional, ANSARI, Jawaher, additional, ATZORI, Francesco, additional, CHIARI, Rita, additional, CAFFO, Orazio, additional, PROCOPIO, Giuseppe, additional, SUNELA, Kaisa, additional, BASSANELLI, Maria, additional, ORTEGA, Cinzia, additional, GRILLONE, Francesco, additional, LANDMESSER, Johannes, additional, MERLER, Sara, additional, MESSINA, Carlo, additional, KÜRONYA, Zsófia, additional, MOSCA, Alessandra, additional, BHUVA, Dipen, additional, SANTINI, Daniele, additional, VAU, Nuno, additional, MORELLI, Franco, additional, INCORVAIA, Lorena, additional, REBUZZI, Sara E., additional, ROVIELLO, Giandomenico, additional, SOARES, Andrey, additional, ZABALZA, Ignacio O., additional, RIZZO, Alessandro, additional, BISONNI, Renato, additional, PIERANTONI, Francesco, additional, SORGENTONI, Giulia, additional, MONTEIRO, Fernando S., additional, BATTELLI, Nicola, additional, BUTI, Sebastiano, additional, and SANTONI, Matteo, additional

Published
2023
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22. Data from Regulatory T-cell Transcriptomic Reprogramming Characterizes Adverse Events by Checkpoint Inhibitors in Solid Tumors

Author

Grigoriou, Maria, primary, Banos, Aggelos, primary, Hatzioannou, Aikaterini, primary, Kloetgen, Andreas, primary, Kouzis, Panagiotis, primary, Aggouraki, Despoina, primary, Zakopoulou, Roubini, primary, Bamias, Giorgos, primary, Kassi, Eva, primary, Mavroudis, Dimitrios, primary, Bamias, Aristotelis, primary, Boumpas, Dimitrios T., primary, Tsirigos, Aristotelis, primary, Gogas, Helen, primary, Alissafi, Themis, primary, and Verginis, Panayotis, primary

Published
2023
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23. Figure S1, Figure S2, Table S1 from Regulatory T-cell Transcriptomic Reprogramming Characterizes Adverse Events by Checkpoint Inhibitors in Solid Tumors

Author

Grigoriou, Maria, primary, Banos, Aggelos, primary, Hatzioannou, Aikaterini, primary, Kloetgen, Andreas, primary, Kouzis, Panagiotis, primary, Aggouraki, Despoina, primary, Zakopoulou, Roubini, primary, Bamias, Giorgos, primary, Kassi, Eva, primary, Mavroudis, Dimitrios, primary, Bamias, Aristotelis, primary, Boumpas, Dimitrios T., primary, Tsirigos, Aristotelis, primary, Gogas, Helen, primary, Alissafi, Themis, primary, and Verginis, Panayotis, primary

Published
2023
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25. Response and outcomes of maintenance avelumab after platinum-based chemotherapy (PBC) in patients (pts) with advanced urothelial carcinoma (aUC): "Real world" experience.

Author

Bakaloudi, Dimitra Rafailia, primary, Talukder, Rafee, additional, Makrakis, Dimitrios, additional, Agarwal, Neeraj, additional, Tripathi, Nishita, additional, Bamias, Aristotelis, additional, Zakopoulou, Roubini, additional, Brown, Jason, additional, Korolewicz, James, additional, Fulgenzi, Claudia A.M., additional, Jindal, Tanya, additional, Murgic, Jure, additional, Fröbe, Ana, additional, Johnson, Jeffrey, additional, Drakaki, Alexandra, additional, Rodríguez-Vida, Alejo, additional, Rey-Cárdenas, Macarena, additional, Alonso Buznego, Lucia Andrea, additional, Khaki, Ali Raza, additional, and Grivas, Petros, additional

Published
2023
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26. Outcomes with immune checkpoint inhibitor (ICI) therapy in patients with FGFR2/3 alterations in advanced urothelial carcinoma (aUC).

Author

Talukder, Rafee, primary, Bakaloudi, Dimitra Rafailia, additional, Makrakis, Dimitrios, additional, Tripathi, Nishita, additional, Agarwal, Neeraj, additional, Jindal, Tanya, additional, Koshkin, Vadim S, additional, Johnson, Jeffrey, additional, Zakharia, Yousef, additional, Brown, Jason, additional, Rey-Cárdenas, Macarena, additional, Castellano, Daniel, additional, Alva, Ajjai Shivaram, additional, Zakopoulou, Roubini, additional, Korolewicz, James, additional, Drakaki, Alexandra, additional, Barata, Pedro C., additional, Grivas, Petros, additional, and Khaki, Ali Raza, additional

Published
2023
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27. New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors

Author

Bamias, Aristotelis, primary, Merseburger, Axel, additional, Loriot, Yohann, additional, James, Nicholas, additional, Choy, Ernest, additional, Castellano, Daniel, additional, Lopez-Rios, F, additional, Calabrò, Fabio, additional, Kramer, Mario, additional, de Velasco, Guillermo, additional, Zakopoulou, Roubini, additional, Tzannis, Kimon, additional, and Sternberg, Cora N, additional

Published
2023
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28. Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

Author

Bamias, Aristotelis, primary, Zakopoulou, Roubini, additional, Tzannis, Kimon, additional, Sakellakis, Minas, additional, Koutsoukos, Konstantinos, additional, Kyriazoglou, Anastasios, additional, Panagiotou, Aikaterini, additional, Armylagos, Stylianos, additional, Rokas, Konstantinos, additional, Gotzias, Dimitrios, additional, Boulouta, Anna, additional, Bozionelou, Vassiliki, additional, Stravodimos, Konstantinos, additional, Varkarakis, Ioannis, additional, Mavroudis, Dimitrios, additional, and Dimopoulos, Meletios-Athanasios, additional

Published
2022
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30. Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study

Author

Bamias, Aristotelis, primary, Tzannis, Kimon, additional, Zakopoulou, Roubini, additional, Sakellakis, Minas, additional, Dimitriadis, John, additional, Papatheodoridi, Alkistis, additional, Rallidis, Loukianos, additional, Halvatsiotis, Panagiotis, additional, Tsiara, Anna, additional, Kaparelou, Maria, additional, Kostouros, Efthymios, additional, Barbarousi, Despina, additional, Koutsoukos, Konstantinos, additional, Fragiadis, Evangelos, additional, Dellis, Athanasios E., additional, Anastasiou, Ioannis, additional, Stravodimos, Konstantinos, additional, Pinitas, Alexandros, additional, Papatsoris, Athanasios, additional, Adamakis, Ioannis, additional, Varkarakis, Ioannis, additional, Fragoulis, Charalampos, additional, Pagoni, Stamatina, additional, Matsouka, Charis, additional, Skolarikos, Andreas, additional, Mitropoulos, Dionysios, additional, Doumas, Konstantinos, additional, Deliveliotis, Charalampos, additional, Constantinides, Constantinos, additional, and Dimopoulos, Meletios-Athanasios, additional

Published
2022
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31. Molecular testing for prostate cancer in Greek patients.

Author

Liontos, Michael, primary, Kunadis, Elena, additional, Svarna, Anna, additional, Skafida, Efthymia, additional, Fiste, Oraianthi, additional, Markellos, Christos, additional, Zakopoulou, Roubini, additional, Papatheodoridi, Alkistis, additional, Andrikopoulou, Angeliki, additional, Kaparelou, Maria, additional, Koutsoukos, Konstantinos, additional, Zagouri, Flora, additional, and Dimopoulos, Meletios A., additional

Published
2022
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32. Association of time to second-line (2L) immune-checkpoint inhibitors (ICI) and outcomes with ICIs in patients (pts) with advanced urothelial carcinoma (aUC).

Author

Makrakis, Dimitrios, primary, Talukder, Rafee, additional, Dawsey, Scott, additional, Carril, Lucia, additional, Stewart, Tyler F., additional, Morales-Barrera, Rafael, additional, Park, Joseph J., additional, Fulgenzi, Claudia Angela Maria, additional, Murgic, Jure, additional, Vather-Wu, Naomi, additional, de Kouchkovsky, Ivan, additional, Devitt, Michael Edward, additional, Di Lorenzo, Giuseppe, additional, Gupta, Kavita, additional, Tripathi, Nishita, additional, Zakopoulou, Roubini, additional, Tripathi, Abhishek, additional, Lu, Eric, additional, Grivas, Petros, additional, and Khaki, Ali Raza, additional

Published
2022
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33. Immunotherapy in Nonendemic Nasopharyngeal Carcinoma: Real-World Data from Two Nonendemic Regions

Author

Economopoulou, Panagiota Pantazopoulos, Anastasios Spathis, Aris and Kotsantis, Ioannis Kyriazoglou, Anastasios Kavourakis, George Zakopoulou, Roubini Chatzidakis, Ioannis Anastasiou, Maria Prevezanou, Maria Resteghini, Carlo Licitra, Lisa and Bergamini, Cristiana Colombo, Elena Caspani, Francesca and Denaro, Nerina Vecchio, Stefania Bonomo, Pierluigi Cossu Rocca, Maria Bertolini, Federica Ferrari, Daris Psyrri, Amanda Bossi, Paolo

Abstract

Background: nasopharyngeal carcinoma (NPC) is a complex disease entity that mainly predominates in endemic regions. Real-world data with immunotherapy from nonendemic regions are limited. Methods: we collected data from patients with recurrent/metastatic (R/M) NPC treated at a center in Greece and 8 centers in Italy. Between 2016 and 2021, 46 patients who were treated with at least one cycle of immune checkpoint inhibitors (ICI) were identified. Herein, we present our results and a review of the literature. Results: assessment of response was available in 42 patients. Overall, 11 patients responded to immunotherapy (Overall Response Rate-ORR 26.2%). Three patients had complete response (CR), and 8 patients had partial response (PR). Disease control rate (DCR) was 61.9%. Median Progression Free Survival (PFS) was 5.6 months and median Overall Survival (OS) was 19.1 months. Responders to ICI improved PFS and OS as compared to that of nonresponders. A lower probability of responding to ICI was shown in patients with more than three metastatic sites (p = 0.073), metastatic disease at initial diagnosis, (p = 0.039) or EBV DNA positive before ICI initiation, (p = 0.074). Decline in EBV DNA levels was found to be statistically significant associated with best response to ICI (p = 0.049). Safety was manageable. Conclusions: among 46 patients with R/M NPC treated with immunotherapy in two nonendemic regions, ORR was 26.2% and durable responses were observed. Low disease burden could serve as a biomarker for response to ICI.

Published
2022

34. DNA Damage Repair: Predictor of Platinum Efficacy in Ovarian Cancer?

Author

Stefanou, Dimitra T. Souliotis, Vassilis L. Zakopoulou, Roubini and Liontos, Michalis Bamias, Aristotelis

Abstract

Ovarian cancer (OC) is the seventh most common type of cancer in women worldwide. Treatment for OC usually involves a combination of surgery and chemotherapy with carboplatin and paclitaxel. Platinum-based agents exert their cytotoxic action through development of DNA damage, including the formation of intra- and inter-strand cross-links, as well as single-nucleotide damage of guanine. Although these agents are highly efficient, intrinsic and acquired resistance during treatment are relatively common and remain a major challenge for platinum-based therapy. There is strong evidence to show that the functionality of various DNA repair pathways significantly impacts tumor response to treatment. Various DNA repair molecular components were found deregulated in ovarian cancer, including molecules involved in homologous recombination repair (HRR), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end-joining (NHEJ), and base excision repair (BER), which can be possibly exploited as novel therapeutic targets and sensitive/effective biomarkers. This review attempts to summarize published data on this subject and thus help in the design of new mechanistic studies to better understand the involvement of the DNA repair in the platinum drugs resistance, as well as to suggest new therapeutic perspectives and potential targets.

Published
2022

35. Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm.

Author

Bamias, Aristotelis, Zakopoulou, Roubini, Tzannis, Kimon, Sakellakis, Minas, Koutsoukos, Konstantinos, Kyriazoglou, Anastasios, Panagiotou, Aikaterini, Armylagos, Stylianos, Rokas, Konstantinos, Gotzias, Dimitrios, Boulouta, Anna, Bozionelou, Vassiliki, Stravodimos, Konstantinos, Varkarakis, Ioannis, Mavroudis, Dimitrios, and Dimopoulos, Meletios-Athanasios

Published
2023
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37. Immunotherapy in Nonendemic Nasopharyngeal Carcinoma: Real-World Data from Two Nonendemic Regions

Author

Economopoulou, Panagiota, primary, Pantazopoulos, Anastasios, additional, Spathis, Aris, additional, Kotsantis, Ioannis, additional, Kyriazoglou, Anastasios, additional, Kavourakis, George, additional, Zakopoulou, Roubini, additional, Chatzidakis, Ioannis, additional, Anastasiou, Maria, additional, Prevezanou, Maria, additional, Resteghini, Carlo, additional, Licitra, Lisa, additional, Bergamini, Cristiana, additional, Colombo, Elena, additional, Caspani, Francesca, additional, Denaro, Nerina, additional, Vecchio, Stefania, additional, Bonomo, Pierluigi, additional, Cossu Rocca, Maria, additional, Bertolini, Federica, additional, Ferrari, Daris, additional, Psyrri, Amanda, additional, and Bossi, Paolo, additional

Published
2021
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38. ERCC1 19007 Polymorphism in Greek Patients with Advanced Urothelial Cancer Treated with Platinum-Based Chemotherapy: Effect of the Changing Treatment Paradigm: A Cohort Study by the Hellenic GU Cancer Group

Author

Bamias, Aristotelis, primary, Koutsoukos, Konstantinos, additional, Gavalas, Nikos, additional, Zakopoulou, Roubini, additional, Tzannis, Kimon, additional, Dedes, Nikos, additional, Boulouta, Anna, additional, Fragkoulis, Charalampos, additional, Kostouros, Eythymios, additional, Dellis, Athanasios, additional, Mitsogiannis, Iraklis, additional, Adamakis, Ioannis, additional, Anastasiou, Ioannis, additional, Skolarikos, Andreas, additional, Papatsoris, Athanasios, additional, Stravodimos, Konstantinos, additional, Ferakis, Nikolaos, additional, Pagoni, Stamatina, additional, Ntoumas, Konstantinos, additional, Mitropoulos, Dionysios, additional, Deliveliotis, Charalambos, additional, Constantinides, Constantinos A., additional, and Dimopoulos, Meletios A., additional

Published
2021
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39. Association of prior local therapy and outcomes with programmed‐death ligand‐1 inhibitors in advanced urothelial cancer

Author

Makrakis, Dimitrios, primary, Talukder, Rafee, additional, Diamantopoulos, Leonidas N., additional, Carril‐Ajuria, Lucia, additional, Castellano, Daniel, additional, De Kouchkovsky, Ivan, additional, Koshkin, Vadim S., additional, Park, Joseph J., additional, Alva, Ajjai, additional, Bilen, Mehmet A., additional, Stewart, Tyler F., additional, McKay, Rana R., additional, Santos, Victor S., additional, Agarwal, Neeraj, additional, Jain, Jayanshu, additional, Zakharia, Yousef, additional, Morales‐Barrera, Rafael, additional, Devitt, Michael E., additional, Grant, Michael, additional, Lythgoe, Mark P., additional, Pinato, David J., additional, Nelson, Ariel, additional, Hoimes, Christopher J., additional, Shreck, Evan, additional, Gartrell, Benjamin A., additional, Sankin, Alex, additional, Tripathi, Abhishek, additional, Zakopoulou, Roubini, additional, Bamias, Aristotelis, additional, Murgic, Jure, additional, Fröbe, Ana, additional, Rodriguez‐Vida, Alejo, additional, Drakaki, Alexandra, additional, Liu, Sandy, additional, Kumar, Vivek, additional, Di Lorenzo, Giuseppe, additional, Joshi, Monika, additional, Isaacsson‐Velho, Pedro, additional, Buznego, Lucia Alonso, additional, Duran, Ignacio, additional, Moses, Marcus, additional, Barata, Pedro, additional, Sonpavde, Guru, additional, Yu, Evan Y., additional, Wright, Jonathan L., additional, Grivas, Petros, additional, and Khaki, Ali Raza, additional

Published
2021
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40. Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review

Author

Kyriazoglou, Anastasios Kaparelou, Maria Goumas, Georgios Liontos, Michael Zakopoulou, Roubini Zografos, Eleni Zygogianni, Anna Dimopoulos, Meletios Athanasios Zagouri, Flora

Subjects
Health Sciences, Επιστήμες Υγείας
Published
2021

41. Immune checkpoint inhibitors (ICI) in advanced upper tract and lower tract urothelial carcinoma (UC): A comparison of outcomes

Author

Esagian, Stepan M. Khaki, Ali Raza Carril-Ajuria, Lucia and Park, Joseph J. Bilen, Mehmet Asim Stewart, Tyler Francis and Santos, Victor Sacristan Jain, Jayanshu Morales-Barrera, Rafael and Devitt, Michael Edward Hoimes, Christopher J. Shreck, Evana and Tripathi, Abhishek Zakopoulou, Roubini Rodriguez-Vida, Alejo and Drakaki, Alexandra Kumar, Vivek Msaouel, Pavlos Koshkin, Vadim S. Petros, Grivas

Published
2021

42. ERCC1 19007 Polymorphism in Greek Patients with Advanced Urothelial Cancer Treated with Platinum-Based Chemotherapy: Effect of the Changing Treatment Paradigm: A Cohort Study by the Hellenic GU Cancer Group

Author

Bamias, Aristotelis Koutsoukos, Konstantinos Gavalas, Nikos and Zakopoulou, Roubini Tzannis, Kimon Dedes, Nikos Boulouta, Anna Fragkoulis, Charalampos Kostouros, Eythymios Dellis, Athanasios Mitsogiannis, Iraklis Adamakis, Ioannis and Anastasiou, Ioannis Skolarikos, Andreas Papatsoris, Athanasios and Stravodimos, Konstantinos Ferakis, Nikolaos Pagoni, Stamatina Ntoumas, Konstantinos Mitropoulos, Dionysios and Deliveliotis, Charalambos Constantinides, Constantinos A. and Dimopoulos, Meletios A.

Abstract

We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.

Published
2021

43. Referral for “Neoadjuvant Chemotherapy” for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes

Author

Dellis, Athanasios, primary, Zakopoulou, Roubini, additional, Kougioumtzopoulou, Andromahi, additional, Tzannis, Kimon, additional, Koutsoukos, Konstantinos, additional, Fragkoulis, Charalampos, additional, Kostouros, Efthymios, additional, Papatsoris, Athanasios, additional, Varkarakis, Ioannis, additional, Stravodimos, Konstantinos, additional, Boutati, Eleni, additional, Pagoni, Stamata, additional, Seferlis, Miltiadis, additional, Chrisofos, Michael, additional, Kouloulias, Vasilios, additional, Ntoumas, Konstantinos, additional, Deliveliotis, Charalambos, additional, Constantinides, Constantine, additional, Dimopoulos, Meletios A, additional, and Bamias, Aristotelis, additional

Published
2021
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44. Response and outcomes to immune checkpoint inhibitors (ICI) in advanced urothelial cancer (aUC) based on prior intravesical BCG.

Author

Talukder, Rafee, primary, Makrakis, Dimitrios, additional, Castellano, Daniel, additional, Koshkin, Vadim S, additional, Alva, Ajjai Shivaram, additional, Stewart, Tyler F., additional, Santos, Victor Sacristan, additional, Jain, Jayanshu, additional, Morales-Barrera, Rafael, additional, Grant, Michael, additional, Nelson, Ariel Ann, additional, Shreck, Evan, additional, Sankin, Alexander, additional, Zakopoulou, Roubini, additional, Rodriguez-Vida, Alejo, additional, Liu, Sandy, additional, Fröbe, Ana, additional, Di Lorenzo, Giuseppe, additional, Grivas, Petros, additional, and Khaki, Ali Raza, additional

Published
2021
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45. Regulatory T-cell Transcriptomic Reprogramming Characterizes Adverse Events by Checkpoint Inhibitors in Solid Tumors

Author

Grigoriou, Maria, primary, Banos, Aggelos, additional, Hatzioannou, Aikaterini, additional, Kloetgen, Andreas, additional, Kouzis, Panagiotis, additional, Aggouraki, Despoina, additional, Zakopoulou, Roubini, additional, Bamias, Giorgos, additional, Kassi, Eva, additional, Mavroudis, Dimitrios, additional, Bamias, Aristotelis, additional, Boumpas, Dimitrios T., additional, Tsirigos, Aristotelis, additional, Gogas, Helen, additional, Alissafi, Themis, additional, and Verginis, Panayotis, additional

Published
2021
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46. Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review

Author

Kyriazoglou, Anastasios, primary, Kaparelou, Maria, additional, Goumas, Georgios, additional, Liontos, Michael, additional, Zakopoulou, Roubini, additional, Zografos, Eleni, additional, Zygogianni, Anna, additional, Dimopoulos, Meletios Athanasios, additional, and Zagouri, Flora, additional

Published
2021
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47. Association between sites of metastases (mets) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

Author

Makrakis, Dimitrios, primary, Diamantopoulos, Leonidas Nikolaos, additional, Koshkin, Vadim S, additional, Alva, Ajjai Shivaram, additional, Bilen, Mehmet Asim, additional, Stewart, Tyler Francis, additional, Santos, Victor Sacristan, additional, Jain, Jayanshu, additional, Morales-Barrera, Rafael, additional, Devitt, Michael E., additional, Carril-Ajuria, Lucia, additional, Nelson, Ariel Ann, additional, Sankin, Alexander, additional, Zakopoulou, Roubini, additional, Pinato, David James, additional, Fröbe, Ana, additional, Joshi, Monika, additional, Sonpavde, Guru, additional, Grivas, Petros, additional, and Khaki, Ali Raza, additional

Published
2021
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48. Immune checkpoint inhibitors (ICI) in advanced upper tract and lower tract urothelial carcinoma (UC): A comparison of outcomes.

Author

Esagian, Stepan M., primary, Khaki, Ali Raza, additional, Carril-Ajuria, Lucia, additional, Park, Joseph J., additional, Bilen, Mehmet Asim, additional, Stewart, Tyler Francis, additional, Santos, Victor Sacristan, additional, Jain, Jayanshu, additional, Morales-Barrera, Rafael, additional, Devitt, Michael Edward, additional, Hoimes, Christopher J., additional, Shreck, Evan, additional, Tripathi, Abhishek, additional, Zakopoulou, Roubini, additional, Rodriguez-Vida, Alejo, additional, Drakaki, Alexandra, additional, Kumar, Vivek, additional, Msaouel, Pavlos, additional, Koshkin, Vadim S, additional, and Grivas, Petros, additional

Published
2021
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49. Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes

Author

Esagian, Stepan M., primary, Khaki, Ali Raza, additional, Diamantopoulos, Leonidas N., additional, Carril‐Ajuria, Lucia, additional, Castellano, Daniel, additional, De Kouchkovsky, Ivan, additional, Park, Joseph J., additional, Alva, Ajjai, additional, Bilen, Mehmet A., additional, Stewart, Tyler F., additional, McKay, Rana R., additional, Santos, Victor S., additional, Agarwal, Neeraj, additional, Jain, Jayanshu, additional, Zakharia, Yousef, additional, Morales‐Barrera, Rafael, additional, Devitt, Michael E., additional, Nelson, Ariel, additional, Hoimes, Christopher J., additional, Shreck, Evan, additional, Gartrell, Benjamin A., additional, Sankin, Alex, additional, Tripathi, Abhishek, additional, Zakopoulou, Roubini, additional, Bamias, Aristotelis, additional, Rodriguez‐Vida, Alejo, additional, Drakaki, Alexandra, additional, Liu, Sandy, additional, Kumar, Vivek, additional, Lythgoe, Mark P., additional, Pinato, David J., additional, Murgic, Jure, additional, Fröbe, Ana, additional, Joshi, Monika, additional, Isaacsson Velho, Pedro, additional, Hahn, Noah, additional, Alonso Buznego, Lucia, additional, Duran, Ignacio, additional, Moses, Marcus, additional, Barata, Pedro, additional, Galsky, Matthew D., additional, Sonpavde, Guru, additional, Yu, Evan Y., additional, Msaouel, Pavlos, additional, Koshkin, Vadim S., additional, and Grivas, Petros, additional

Published
2021
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50. The Immunoscore in Localized Urothelial Carcinoma Treated with Neoadjuvant Chemotherapy: Clinical Significance for Pathologic Responses and Overall Survival

Author

Nassif, Elise F., primary, Mlecnik, Bernhard, additional, Thibault, Constance, additional, Auvray, Marie, additional, Bruni, Daniela, additional, Colau, Alexandre, additional, Compérat, Eva, additional, Bindea, Gabriela, additional, Catteau, Aurélie, additional, Fugon, Aurélie, additional, Boquet, Isabelle, additional, Martel, Marine, additional, Camparo, Philippe, additional, Colin, Pierre, additional, Zakopoulou, Roubini, additional, Bamias, Aristotelis, additional, Bennamoun, Mostefa, additional, Barthere, Xavier, additional, D’acremont, Bruno, additional, Lefevre, Marine, additional, Audenet, Francois, additional, Mejean, Arnaud, additional, Verkarre, Virginie, additional, Oudard, Stéphane, additional, and Galon, Jérôme, additional

Published
2021
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