Browsing by Author "Castro-Oliden, V"

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Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study
(Elsevier BV, 2021) Sun, JM; Shen, L; Shah, MA; Enzinger, P; Adenis, A; Doi, T; Kojima, T; Metges, JP; Li, Z; Kim, SB; Cho, BC; Mansoor, W; Li, SH; Sunpaweravong, P; Maqueda, MA; Goekkurt, E; Hara, H; Antunes, L; Fountzilas, C; Tsuji, A; Castro-Oliden, V; Liu Q; Shah S; Bhagia P; Kato K; KEYNOTE-590 Investigators.
Background: First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer. Methods: We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment. Findings: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group. Interpretation: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population.
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial
(Elsevier, 2023) Rha, SY; Oh, DY; Yañez, P; Bai, Y; Ryu, MH; Lee, J; Rivera, F; Alves, GV; Garrido, M; Shiu, KK; Fernández, MG; Li, J; Lowery, MA; Çil, T; Cruz, FM; Qin, S; Luo, S; Pan, H; Wainberg, ZA; Yin, L; Bordia, S; Bhagia, P; Wyrwicz, LS; KEYNOTE-859 investigators; Castro-Oliden, V
Background: PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. Methods: KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1-5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1-14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete. Findings: Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0-38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9-14·0] vs 11·5 months [10·6-12·1]; hazard ratio [HR] 0·78 [95% CI 0·70-0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6-14·2] vs 11·4 months [10·5-12·0]; 0·74 [0·65-0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8-19·3] vs 11·8 months [10·3-12·7]; 0·65 [0·53-0·79]; p<0·0001). The most common grade 3-5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified. Interpretation: Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
Sarcoma European and Latin American Network (SELNET) Recommendations on Prioritization in Sarcoma Care During the COVID-19 Pandemic
(Oxford University Press, 2020) Martin-Broto, J; Hindi, N; Aguiar S, Jr; Badilla-González, R; Castro-Oliden, V; Chacón, M; Correa-Generoso, R; de Álava, E; Donati, DM; Eriksson, M; Falla-Jimenez, M; German, G; Gobo Silva, ML; Gouin, F; Gronchi, A; Haro-Varas, JC; Jiménez-Brenes, N; Kasper, B; Lopes de Mello, CA; Maki, R; Martínez-Delgado, P; Martínez-Said, H; Martinez-Tlahuel, JL; Morales-Pérez, JM; Muñoz-Casares, FC; Nakagawa, SA; Ortiz-Cruz, EJ; Palmerini, E; Patel, S; Moura, DS; Stacchiotti, S; Sunyach, MP; Valverde, CM; Waisberg, F; Blay, JY
Background: The COVID‐19 outbreak has resulted in collision between patients infected with SARS‐CoV‐2 and those with cancer on different fronts. Patients with cancer have been impacted by deferral, modification, and even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precautionary principle, have been proposed for cancer care during COVID‐19 era. We present here a consensus on prioritizing recommendations across the continuum of sarcoma patient care. Material and Methods: A total of 125 recommendations were proposed in soft‐tissue, bone, and visceral sarcoma care. Recommendations were assigned as higher or lower priority if they cannot or can be postponed at least 2–3 months, respectively. The consensus level for each recommendation was classified as “strongly recommended” (SR) if more than 90% of experts agreed, “recommended” (R) if 75%–90% of experts agreed and “no consensus” (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the Sarcoma European‐Latin American Network (SELNET) consortium participated, including countries in the Americas and Europe. The European Society for Medical Oncology‐Magnitude of clinical benefit scale was applied to systemic‐treatment recommendations to support prioritization. Results: There were 80 SRs, 35 Rs, and 10 NCs among the 125 recommendations issued and completed by 31 multidisciplinary sarcoma experts. The consensus was higher among the 75 higher‐priority recommendations (85%, 12%, and 3% for SR, R, and NC, respectively) than in the 50 lower‐priority recommendations (32%, 52%, and 16% for SR, R, and NC, respectively). Conclusion: The consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a tool for sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.
SELNET clinical practice guidelines for bone sarcoma
(Elsevier Ireland Ltd, 2022) Blay, JY; Palmerini, E; Bollard, J; Aguiar, S; Angel, M; Araya, B; Badilla, R; Bernabeu, D; Campos, F; Chs, CS; Carvajal Montoya, A; Casavilca-Zambrano, S; Castro-Oliden, V; Chacón, M; Clara-Altamirano, MA; Collini, P; Correa Genoroso, R; Costa, FD; Cuellar, M; Dei Tos, AP; Dominguez Malagon, HR; Donati, DM; Dufresne, A; Eriksson, M; Farias-Loza, M; Frezza, AM; Frisoni, T; Garcia-Ortega, DY; Gerderblom, H; Gouin, F; Gómez-Mateo, MC; Gronchi, A; Haro, J; Hindi, N; Huanca, L; Jimenez, N; Karanian, M; Kasper, B; Lopes, A; Lopes David, BB; Lopez-Pousa, A; Lutter, G; Maki, RG; Martinez-Said, H; Martinez-Tlahuel, JL; Mello, CA; Morales Pérez, JM; Moura, DS; Nakagawa, SA; Nascimento, AG; Ortiz-Cruz, EJ; Patel, S; Pfluger, Y; Provenzano, S; Righi, A; Rodriguez, A; Santos, TG; Scotlandi, K; Mlg S, Soulé T; Stacchiotti, S; Valverde, CM; Waisberg, F; Zamora Estrada, E; Martin-Broto, J
Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.
SELNET clinical practice guidelines for soft tissue sarcoma and GIST
(W.B. Saunders Ltd, 2022) Blay, JY; Hindi, N; Bollard, J; Aguiar, S Jr; Angel, M; Araya, B; Badilla, R; Bernabeu, D; Campos, F; Caro-Sánchez, CHS; Carvajal, B; Carvajal Montoya, A; Casavilca-Zambrano, S; Castro-Oliden, V; Chacón, M; Clara, M; Collini, P; Correa Genoroso, R; Costa, FD; Cuellar, M; Dei Tos, AP; Dominguez Malagon, HR; Donati, D; Dufresne, A; Eriksson, M; Farias-Loza, M; Fernandez, P; Frezza, AM; Frisoni, T; Garcia-Ortega, DY; Gelderblom, H; Gouin, F; Gómez-Mateo, MC; Gronchi, A; Haro, J; Huanca, L; Jimenez, N; Karanian, M; Kasper, B; Lopes David, BB; Lopez-Pousa, A; Lutter, G; Martinez-Said, H; Martinez-Tlahuel, J; Mello, CA; Morales Pérez, JM; Moura David, S; Nascimento, AG; Ortiz-Cruz, EJ; Palmerini, E; Patel, S; Pfluger, Y; Provenzano, S; Righi, A; Rodriguez, A; Salas, R; Santos, TTG; Scotlandi, K; Soule, T; Stacchiotti, S; Valverde, C; Waisberg, F; Zamora Estrada, E; Martin-Broto, J
Soft tissue sarcoma (STS) and gastrointestinal tumors (GIST) encompass > 80 different histologic subtypes. Clinical practice guidelines for STS and GIST still lack in Latin-American countries. Tailored clinical guidelines are instrumental to improve outcome in sarcoma patients in LatinAmerican countries. This is the first review establishing STS and GIST guidelines for the purpose of LatinAmerican clinical practices to our knowledge.
Temozolomide and capecitabine regimen as first-line treatment in advanced gastroenteropancreatic neuroendocrine tumors at a Latin American reference center
(Baishideng Publishing Group Inc, 2024) Cruz-Diaz, WE; Paitan, V; Medina, J; Flores, R; Haro-Varas, J; Mantilla, R; Castro-Oliden, V
BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen (TEMCAP) exhibits a certain level of efficacy in treating advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). However, published data from Peru are limited. We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population. AIM To evaluate overall survival (OS) in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima-Perú. METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN. A total of thirty-eight patients were included in the final analysis: Thirty-five received TEMCAP as a first-line treatment, and three as a second-line treatment. The primary objective was to evaluate OS. The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS The median age of the patients was 52 years (range 24–77 years), and 53.3% were female. The most common symptoms at diagnosis were abdominal pain in 31 patients (81.6%). Primary tumors included 12 in the rectum (31.6%), 11 in the pancreas (28.9%), 3 in the ileum (7.9%), 2 in the mesentery (5.3%), 2 in the small intestine (5.3%), 1 in the appendix (2.6%), 1 in the stomach (2.6%) and 6 cases of liver metastasis of unknown primary (15.8%). Five were neuroendocrine tumors (NET) G1 (13.2%), 33 were NET G2 (86.8%), five had Ki67 < 3% (13.2%), and 33 had Ki67 between 3% and 20% (86.8%). TEMCAP was administered to 35 (92.1%) patients as first-line treatment. OS at 12, 36, and 60 months was estimated in 80%, 66%, and 42%, respectively, with a median OS of 49 months. CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible. © The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.