MARIA IGNEZ FREITAS MELRO BRAGHIROLI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial(2020) SHITARA, Kohei; CUTSEM, Eric Van; BANG, Yung-Jue; FUCHS, Charles; WYRWICZ, Lucjan; LEE, Keun-Wook; KUDABA, Iveta; GARRIDO, Marcelo; CHUNG, Hyun Cheol; LEE, Jeeyun; CASTRO, Hugo Raul; MANSOOR, Wasat; BRAGHIROLI, Maria Ignez; KARASEVA, Nina; CAGLEVIC, Christian; VILLANUEVA, Luis; GOEKKURT, Eray; SATAKE, Hironaga; ENZINGER, Peter; ALSINA, Maria; BENSON, Al; CHAO, Joseph; KO, Andrew H.; WAINBERG, Zev A.; KHER, Uma; SHAH, Sukrut; KANG, S. Peter; TABERNERO, JosepIMPORTANCE Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need. OBJECTIVE To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand l(PD-L1) combined positive score (CP5) of lor greater. DESIGN, SETTING. AND PARTICIPANTS The phase 3 KEYNOTE -062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1CPS of lor greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017. INTERVENTIONS Patients were randomized 1:1:1to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2twice daily), or chemotherapy plus placebo, every 3 weeks. MAIN OUTCOME ABD MEASURES Primary end points were overall survival (OS) and progression -free survival (PFS) in patients with PD-L1CPS of lor greater or 10 or greater. RE.5).K.Ts A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of lor greater (median, 10.6 vs 11.1months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1]8). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of lor greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CP5 of lor greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03; P =.05) or CP5 of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P =.16) or for PFS in patients with CPS of lor greater (6.9 vs 6.4 months; HR, 0.84; 95% Cl, 0.70-1.02; P =.04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively. CONCLUSIONS AND RELEVANCE This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested.
conferenceObject Pembrolizumab with or without chemotherapy vs chemotherapy in patients with advanced G/GEJ cancer (GC) including outcomes according to Microsatellite Instability-High (MSI-H) status in KEYNOTE-062(2019) SHITARA, K.; CUTSEM, E. Van; BANG, Y-J.; FUCHS, C. S.; WYRWICZ, L.; LEE, K. W.; KUDABA, I.; GARRIDO, M.; CHUNG, H. Cheol; CASTRO, H. R.; MANSOOR, W.; BRAGHIROLI, M. I. F. M.; GOEKKURT, E.; CHAO, J.; WAINBERG, Z. A.; KHER, U.; SHAH, S.; KANG, S. P.; TABERNERO, J.conferenceObject Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): 29-month (mo) follow-up from CheckMate 648(2023) GREIL, R.; KATO, K.; AJANI, J.; DOKI, Y.; XU, J.; WYRWICZ, L.; MOTOYAMA, S.; OGATA, T.; KAWAKAMI, H.; HSU, C. -H; ADENIS, A.; HAJBI, F. El; BARTOLOMEO, M. Di; BRAGHIROLI, M. Ignez; HOLTVED, E.; MURPHY, M. Blum; PATEL, A.; HU, N.; MATSUMURA, Y.; CHAU, I; KITAGAWA, Y.- Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma(2022) DOKI, Y.; AJANI, J. A.; KATO, K.; XU, J.; WYRWICZ, L.; MOTOYAMA, S.; OGATA, T.; KAWAKAMI, H.; HSU, C. -H.; ADENIS, A.; HAJBI, F. El; BARTOLOMEO, M. Di; BRAGHIROLI, M. I.; HOLTVED, E.; OSTOICH, S. A.; KIM, H. R.; UENO, M.; MANSOOR, W.; YANG, W. -C.; LIU, T.; BRIDGEWATER, J.; MAKINO, T.; XYNOS, I.; LIU, X.; LEI, M.; KONDO, K.; PATEL, A.; GRICAR, J.; CHAU, I.; KITAGAWA, Y.BACKGROUND First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma. METHODS In this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients). RESULTS A total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P=0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P=0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P=0.01). Among patients with tumor-cell PD-L1 expression of 1% or greater, a significant progression-free survival benefit was also seen with nivolumab plus chemotherapy over chemotherapy alone (hazard ratio for disease progression or death, 0.65; 98.5% CI, 0.46 to 0.92; P=0.002) but not with nivolumab plus ipilimumab as compared with chemotherapy. The incidence of treatment-related adverse events of grade 3 or 4 was 47% with nivolumab plus chemotherapy, 32% with nivolumab plus ipilimumab, and 36% with chemotherapy alone. CONCLUSIONS Both first-line treatment with nivolumab plus chemotherapy and first-line treatment with nivolumab plus ipilimumab resulted in significantly longer overall survival than chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma, with no new safety signals identified.
conferenceObject Nivolumab (NIVO) plus chemotherapy (chemo) or NIVO plus ipilimumab (IPI) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first report of the CheckMate 648 study(2021) GREIL, R.; CHAU, I; DOKI, Y.; AJANI, J. A.; XU, J.; WYRWICZ, L.; MOTOYAMA, S.; OGATA, T.; KAWAKAMI, H.; HSU, C. -H; ADENIS, A.; HAJBI, F. el; BARTOLOMEO, M. Di; BRAGHIROLI, Ignez M.; HOLTVED, E.; XYNOS, I; LIU, X.; LEI, M.; KONDO, K.; KATO, K.; KITAGAWA, Y.- Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Expanded efficacy and safety analyses from CheckMate 648(2022) CHAU, I.; AJANI, J.; DOKI, Y.; XU, J.; WYRWICZ, L.; MOTOYAMA, S.; OGATA, T.; KAWAKAMI, H.; HSU, C.; ADENIS, A.; HAJBI, F. El; BARTOLOMEO, M. Di; BRAGHIROLI, M.; HOLTVED, E.; MURPHY, M. Blum; ABDULLAEV, S.; SOLEYMANI, S.; LEI, M.; KATO, K.; KITAGAWA, Y.
conferenceObject Pembrolizumab plus chemotherapy for advanced G/GEJ adenocarcinoma (GC): The phase III KEYNOTE-062 study(2019) CHUNG, H. C.; BANG, Y-J.; TABERNERO, J.; CUTSEM, E. Van; FUCHS, C. S.; WYRWICZ, L.; LEE, K-W.; KUDABA, I.; GARRIDO, M.; CASTRO, H.; MANSOOR, W.; BRAGHIROLI, M. I.; GOEKKURT, E.; CHAO, J.; WAINBERG, Z. A.; KHER, U.; SHAH, S.; SHITARA, K.