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1. Addressing the unmet needs of patients with BRAF-mutated melanoma in Latin America: Expert perspective

Author

Pamela Salman, Andreia Cristina de Melo, Mariana Rico-Restrepo, Jeronimo Rodriguez, Andrea Russi, Rafael Aron Schmerling, Angela Zambrano, and Gabriela Cinat

Subjects
BRAF-mutated melanoma, Latin America, melanoma, V600E, access, health policy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF-status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF-mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma’s time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment.

Published
2023
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2. Innovative Methodology for Strengthening a Multidisciplinary Team Approach in Cities in Low- and Middle-Income Countries

Author

Vanessa Eaton, Angela Zambrano, Valeria Sanabria, Roberto Lopez, Ishmael Kyei, Rai Mra, Vanessa Sarchet, Megan Kremzier, Josep Borras, Thet Ko Aung, Rebecca Morton Doherty, Susan Henshall, and Rolando Camacho

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSEDelivering high-quality cancer care to patients through a multidisciplinary team (MDT) care approach remains a challenge, particularly in low- and middle-income countries characterized by fragmented health systems and limited human resources for cancer care. City Cancer Challenge (C/Can) is supporting cities in low- and middle-income countries as they work to improve access to equitable quality cancer care. C/Can has developed an innovative methodology to address the MDT gap, piloted in four cities—Asunciòn, Cali, Kumasi, and Yangon.METHODSCollaborating with a network of partners, C/Can and ASCO have developed a package of technical cooperation support focusing on two priority areas that have emerged as core needs: first developing consensus-based, city-wide patient management guidelines for the most common cancers and second, building capacity for the implementation of MDTs in institutions providing cancer care in the city.RESULTSThe real-time application of C/Can's MDT approach in Cali and Asuncion underlined the importance of engaging the right stakeholders early on and embedding MDT guidelines in local and national regulatory frameworks to achieve their sustainable uptake. The results in Cali and Asuncion were essential for informing the process in Yangon, asserting the clear benefits of city-to-city knowledge exchange. Finally, the global COVID-19 pandemic prompted a rapid adaptation of the methodology from an in-person to virtual format; the unexpected success of the virtual program in Kumasi has led to its application in subsequent C/Can cities.CONCLUSIONThe application of C/Can's methodology in this first set of cities has reinforced not only the importance of both resource appropriate guidelines and a highly trained health workforce but also the need for commitment to work across institutions and disciplines.

Published
2022
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3. Los núcleos integradores en la Pedagogía de la Química y la Biología: una experiencia de enseñanza y aprendizaje

Author

Silvia Imbaquingo Maigua and Angela Zambrano Carranza

Subjects
interdisciplinariedad, núcleo integrador, multidisciplinariedad, transdiciplinariedad, proceso de enseñanza y aprendizaje, condiciones de aprendizaje, Theory and practice of education, LB5-3640
Abstract

INTRODUCCIÓN. La implementación del núcleo integrador de saberes en la Carrera de Pedagogía de las Ciencias Experimentales, Química y Biología, como innovación pedagógica en el proceso de enseñanza y aprendizaje, consistió en consolidar un bloque de contenidos de las materias de Química, Biología y Ciencias de la Tierra. MÉTODO. Durante el ejercicio de la experiencia se diversificaron las metodologías pedagógicas y las condiciones y entornos de aprendizaje, con un trabajo más cercano entre docentes y estudiantes al promover espacios de trabajo y reflexión inter, multi y transdisciplinario de los temas propuestos en el núcleo integrador, fortalecidos con enfoques transversales como género, etnicidad, interculturalidad, derechos humanos y sustentabilidad. RESULTADOS. Los resultados del proceso reflejaron una mejor comprensión de la teoría contextualizada a la realidad socioambiental, el desarrollo del pensamiento crítico y la predisposición de los estudiantes para actuar responsablemente frente al ambiente. DISCUSIÓN. La experiencia constituyó una manera diferente de abordar los contenidos científicos de las disciplinas que conforman la malla curricular, superando el asignaturismo tradicional que compartimenta el conocimiento de estas ciencias, estimula el trabajo autónomo y promueve la corresponsabilidad social en la gestión de los recursos naturales.

Published
2019
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6. Indigenous Communities in Colombia: A Cultural and Holistic View of Cancer Management

Author

Angela Zambrano Harvey, Francisco Javier Bonilla‐Escobar, Alejandra Hidalgo, Luis Gabriel Parra‐Lara, Diana Marcela Mendoza‐Urbano, Zeynara Zapata Izquierdo, and Sara Gabriela Pacichana Quinayáz

Subjects
Cancer Research, Oncology
Abstract

Cancer is one of the most burdening global health challenges. Indigenous communities are at high risk for worse healthcare outcomes because of inequalities in the incidence, prevalence, and mortality of oncological diseases, that arise from socioeconomic, racial, cultural, religious beliefs, and ethnic factors. Their perception about themselves is closely related to what affects their territory, making them possess a profound rooted feeling with their surroundings, and intense spiritual believes. Consequently, the disease process is linked to physical and emotional imbalances and alterations in their territory. Researchers from United States, Canada, New Zealand, and Australia have worked diligently to learn about barriers to cancer management among these populations. Unfortunately, robust cancer data is lacking for most of the world's Indigenous, leading to obstacles in information systems and consequently, inequities in healthcare with the perpetuation of the problem. Therefore, a better understanding of cancer as a global health problem is required. This study aims to propose a holistic and culturally adapted framework to improve cancer health services and outcomes among Indigenous peoples in Colombia. This article is protected by copyright. All rights reserved.

Published
2022

7. Survival of patients with mucosal melanoma in Cali, Colombia: a retrospective cohort study

Author

Ana M. García, Luis G. Parra-Lara, Diana M. Mendoza-Urbano, Juan C. Bravo, and Ángela Zambrano Harvey

Subjects
Mucosal melanoma, Neoplasm staging, Survival, Immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Mucosa melanoma is a rare condition with aggressive behavior and a less favorable prognosis compared to cutaneous melanoma. The objective of this study was to estimate the overall survival and clinical outcomes of patients diagnosed with mucosal melanoma in a Colombian hospital. Methods A retrospective cohort study was conducted at Fundación Valle del Lili, a single center located in Cali, Colombia. Patients aged ≥ 18 years, both sexes, diagnosed with mucosal melanoma by histopathology study were included between 2010–2019. Patients who received extra-institutional treatment or whose vital status was unknown during follow-up were excluded. Demographic, clinical and laboratory data were obtained from medical records and laboratory and pathology databases. A descriptive analysis was performed. Survival analysis was conducted using the Kaplan–Meier method. Results A total of 23 patients were included. Median age was 63 years old (IQR: 57–68) and 52.2% were woman. Clinical stage was 34.8% early, 26.1% locally advanced and 39.1% metastatic. The main primary locations were nasopharynx (30.4%), genitals (26.1%), rectum (21.7%), oral cavity (13%) and paranasal sinuses (8.7%). The majority received surgery (30.4%) and immunotherapy (26.1%) as first line treatment. Overall survival at one year was 80.8%, at three years 44.3%, and at five years 36.9%. Conclusion Mucosal melanoma is a rare, aggressive disease with adverse oncological outcomes due to late diagnosis and limited treatment options. This study provides real-world data in a single-center of Colombia.

Published
2024
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8. Extracción automatizada de información en español de texto libre de informes de patología oncológica.

Author

Marcela Mendoza-Urbano, Diana, Felipe Garcia, Johan, Sebastian Moreno, Juan, Carlos Bravo-Ocaña, Juan, José Riascos, Alvaro, Harvey, Angela Zambrano, and Prada, Sergio I.

Subjects
NATURAL language processing, HUMAN services programs, CANCER patients, SOFTWARE architecture, INFORMATION retrieval, AUTOMATION, MEDICAL records, ELECTRONIC health records, ALGORITHMS, ONCOLOGY, WORLD Wide Web
Abstract

Copyright of Colombia Medica is the property of Universidad del Valle and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023
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9. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048)

Author

Barbara Burtness, Kevin J Harrington, Richard Greil, Denis Soulières, Makoto Tahara, Gilberto de Castro, Amanda Psyrri, Neus Basté, Prakash Neupane, Åse Bratland, Thorsten Fuereder, Brett G M Hughes, Ricard Mesía, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Ruey-Long Hong, René González Mendoza, Ananya Roy, Yayan Zhang, Burak Gumuscu, Jonathan D Cheng, Fan Jin, Danny Rischin, Guillermo Lerzo, Marcelo Tatangelo, Mirta Varela, Juan Jose Zarba, Michael Boyer, Hui Gan, Bo Gao, Brett Hughes, Girish Mallesara, Anne Taylor, Martin Burian, Carlos Henrique Barrios, Dalvaro Oliveira de Castro Junior, Gilberto Castro, Fabio Andre Franke, Gustavo Girotto, Iane Pinto Figueiredo Lima, Ulisses Ribaldo Nicolau, Gustavo Dix Junqueira Pinto, Lucas Santos, Ana-Paula Victorino, Neil Chua, Felix Couture, Richard Gregg, Aaron Hansen, John Hilton, Joy McCarthy, Denis Soulieres, Rodrigo Ascui, Pablo Gonzalez, Luis Villanueva, Marco Torregroza, Angela Zambrano, Petra Holeckova, Zdenek Kral, Bohuslav Melichar, Jana Prausova, Milan Vosmik, Maria Andersen, Niels Gyldenkerne, Hannes Jurgens, Kadri Putnik, Petri Reinikainen, Viktor Gruenwald, Simon Laban, Gerasimos Aravantinos, Ioannis Boukovinas, Vassilis Georgoulias, Dora Kwong, Yousuf Al-Farhat, Tibor Csoszi, Jozsef Erfan, Geza Horvai, Laszlo Landherr, Eva Remenar, Agnes Ruzsa, Judit Szota, Salem Billan, Iris Gluck, Orit Gutfeld, Aron Popovtzer, Marco Benasso, Simona Bui, Vittorio Ferrari, Lisa Licitra, Franco Nole, Takashi Fujii, Yasushi Fujimoto, Nobuhiro Hanai, Hiroki Hara, Koji Matsumoto, Kenji Mitsugi, Nobuya Monden, Masahiro Nakayama, Kenji Okami, Nobuhiko Oridate, Kiyoto Shiga, Yasushi Shimizu, Masashi Sugasawa, Masanobu Takahashi, Shunji Takahashi, Kaoru Tanaka, Tsutomu Ueda, Hironori Yamaguchi, Tomoko Yamazaki, Ryuji Yasumatsu, Tomoya Yokota, Tomokazu Yoshizaki, Iveta Kudaba, Zinaida Stara, Soon Keat Cheah, Jose Aguilar Ponce, Rene Gonzalez Mendoza, Carlos Hernandez Hernandez, Francisco Medina Soto, Jan Buter, Ann Hoeben, S. Oosting, Karijn Suijkerbuijk, Aase Bratland, Marianne Brydoey, Renzo Alvarez, Luis Mas, Priscilla Caguioa, John Querol, Eugenio Emmanuel Regala, Maria Belen Tamayo, Ellie May Villegas, Andrzej Kawecki, Andrey Karpenko, Arkadiy Klochikhin, Alexey Smolin, Oleg Zarubenkov, Boon Cher Goh, Graham Cohen, Johanna du Toit, Christa Jordaan, Gregory Landers, Paul Ruff, Waldemar Szpak, Neonyana Tabane, Irene Brana, Lara Iglesias Docampo, Javier Lavernia, Ricard Mesia, Edvard Abel, Valentina Muratidu, Niels Nielsen, Valerie Cristina, Sacha Rothschild, Hung-Ming Wang, Muh-Hwa Yang, Su-Peng Yeh, Chia-Jui Yen, Nopadol Soparattanapaisarn, Virote Sriuranpong, Sercan Aksoy, Irfan Cicin, Meltem Ekenel, Hakan Harputluoglu, Ozgur Ozyilkan, Kevin Harrington, Sanjiv Agarwala, Haythem Ali, Robert Alter, Daniel Anderson, Justine Bruce, Nicholas Campbell, Miguel Conde, John Deeken, William Edenfield, Lawrence Feldman, Elizabeth Gaughan, Basem Goueli, Balazs Halmos, Upendra Hegde, Brian Hunis, Robert Jotte, Anand Karnad, Saad Khan, Noel Laudi, Douglas Laux, Danko Martincic, Steven McCune, Dean McGaughey, Krzysztof Misiukiewicz, Deborah Mulford, Eric Nadler, Johannes Nunnink, James Ohr, Meaghan O'Malley, Brian Patson, Doru Paul, Elizabeta Popa, Steven Powell, Rebecca Redman, Vincent Rella, Chaio Rocha Lima, Abirami Sivapiragasam, Yungpo Su, Ammar Sukari, Stuart Wong, Emrullah Yilmaz, Jeffrey Yorio, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Oncology, Male, Humanized/therapeutic use, Antimetabolites, Cetuximab, Phases of clinical research, Pembrolizumab, 030204 cardiovascular system & hematology, Antineoplastic/therapeutic use, Cetuximab/therapeutic use, Antineoplastic Agents, Immunological, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Monoclonal, Squamous Cell Carcinoma of Head and Neck/drug therapy, 030212 general & internal medicine, Antineoplastic Agents, Immunological/therapeutic use, education.field_of_study, General Medicine, Middle Aged, Antimetabolites, Antineoplastic/therapeutic use, Progression-Free Survival, Antibodies, Monoclonal, Humanized/therapeutic use, Head and Neck Neoplasms, Female, Fluorouracil, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Population, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Fluorouracil/therapeutic use, Antibodies, 03 medical and health sciences, Immunological/therapeutic use, Internal medicine, medicine, Humans, Progression-free survival, education, Aged, Performance status, Squamous Cell Carcinoma of Head and Neck, business.industry, Head and Neck Neoplasms/drug therapy, medicine.disease, Interim analysis, Head and neck squamous-cell carcinoma, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract

BACKGROUND: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.METHODS: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031.FINDINGS: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45-0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64-0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71-1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63-0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45-0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53-0·80], pINTERPRETATION: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC.FUNDING: Merck Sharp & Dohme.

Published
2019

10. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Author

Tony S K Mok, Yi-Long Wu, Iveta Kudaba, Dariusz M Kowalski, Byoung Chul Cho, Hande Z Turna, Gilberto Castro, Vichien Srimuninnimit, Konstantin K Laktionov, Igor Bondarenko, Kaoru Kubota, Gregory M Lubiniecki, Jin Zhang, Debra Kush, Gilberto Lopes, Grigory Adamchuk, Myung-Ju Ahn, Aurelia Alexandru, Ozden Altundag, Anna Alyasova, Orest Andrusenko, Keisuke Aoe, Antonio Araujo, Osvaldo Aren, Oscar Arrieta Rodriguez, Touch Ativitavas, Oscar Avendano, Fernando Barata, Carlos Henrique Barrios, Carlos Beato, Per Bergstrom, Daniel Betticher, Larisa Bolotina, Michiel Botha, Sayeuri Buddu, Christian Caglevic, Andres Cardona, Hugo Castro, Filiz Cay Senler, Carlos Alexandre Sydow Cerny, Alvydas Cesas, Gee-Chen Chan, Jianhua Chang, Gongyan Chen, Xi Chen, Susanna Cheng, Ying Cheng, Nelly Cherciu, Chao-Hua Chiu, Saulius Cicenas, Daniel Ciurescu, Graham Cohen, Marcos Andre Costa, Pongwut Danchaivijitr, Flavia De Angelis, Sergio Jobim de Azevedo, Mircea Dediu, Tsvetan Deliverski, Pedro Rafael Martins De Marchi, Flor de The Bustamante Valles, Zhenyu Ding, Boyan Doganov, Lydia Dreosti, Ricardo Duarte, Regina Edusma-Dy, Sergey Emelyanov, Mustafa Erman, Yun Fan, Luis Fein, Jifeng Feng, David Fenton, Gustavo Fernandes, Carlos Ferreira, Fabio Andre Franke, Helano Freitas, Yasuhito Fujisaka, Hector Galindo, Christina Galvez, Doina Ganea, Nuno Gil, Gustavo Girotto, Erdem Goker, Tuncay Goksel, Gonzalo Gomez Aubin, Luis Gomez Wolff, Hakan Griph, Mahmut Gumus, Jacqueline Hall, Gregory Hart, Libor Havel, Jianxing He, Yong He, Carlos Hernandez Hernandez, Venceslau Hespanhol, Tomonori Hirashima, Chung Man James Ho, Atsushi Horiike, Yukio Hosomi, Katsuyuki Hotta, Mei Hou, Soon Hin How, Te-Chun Hsia, Yi Hu, Masao Ichiki, Fumio Imamura, Oleksandr Ivashchuk, Yasuo Iwamoto, Jana Jaal, Jacek Jassem, Christa Jordaan, Rosalyn Anne Juergens, Diego Kaen, Ewa Kalinka-Warzocha, Nina Karaseva, Boguslawa Karaszewska, Andrzej Kazarnowicz, Kazuo Kasahara, Nobuyuki Katakami, Terufumi Kato, Tomoya Kawaguchi, Joo Hang Kim, Kazuma Kishi, Vitezslav Kolek, Marchela Koleva, Petr Kolman, Leona Koubkova, Ruben Kowalyszyn, Dariusz Kowalski, Krassimir Koynov, Doran Ksienski, Takayasu Kurata, Gerli Kuusk, Lyudmila Kuzina, Ibolya Laczo, Guia Elena Imelda Ladrera, Konstantin Laktionov, Gregory Landers, Sergey Lazarev, Guillermo Lerzo, Krzysztof Lesniewski Kmak, Wei Li, Chong Kin Liam, Igor Lifirenko, Oleg Lipatov, Xiaoqing Liu, Zhe Liu, Sing Hung Lo, Valeria Lopes, Karla Lopez, Shun Lu, Gaston Martinengo, Luis Mas, Marina Matrosova, Rumyana Micheva, Zhasmina Milanova, Lucian Miron, Tony Mok, Matias Molina, Shuji Murakami, Yasuharu Nakahara, Tien Quang Nguyen, Takashi Nishimura, Adrian Ochsenbein, Tatsuo Ohira, Ronny Ohman, Choo Khoon Ong, Gyula Ostoros, Xuenong Ouyang, Elena Ovchinnikova, Ozgur Ozyilkan, Lubos Petruzelka, Xuan Dung Pham, Pablo Picon, Bela Piko, Artem Poltoratsky, Olga Ponomarova, Patrice Popelkova, Gunta Purkalne, Shukui Qin, Rodryg Ramlau, Bernardo Rappaport, Felipe Rey, Eduardo Richardet, Jaromir Roubec, Paul Ruff, Andrii Rusyn, Hideo Saka, Jorge Salas, Mario Sandoval, Lucas Santos, Toshiyuki Sawa, Kasan Seetalarom, Mesut Seker, Nobuhiko Seki, Freddy Seolwane, Lucinda Shepherd, Sergii Shevnya, Andrea Kazumi Shimada, Yaroslav Shparyk, Ivan Sinielnikov, Daniela Sirbu, Oren Smaletz, Joao Paulo Holanda Soares, Aumkhae Sookprasert, Giovanna Speranza, Virote Sriuranpong, Zinaida Stara, Wu-Chou Su, Shunichi Sugawara, Waldemar Szpak, Kazuhisa Takahashi, Nagio Takigawa, Hiroshi Tanaka, Jerry Tan Chun Bing, Qiyou Tang, Pavel Taranov, Hermes Tejada, Lye Mun Tho, Yoshitaro Torii, Dmytro Trukhyn, Maria Turdean, Hande Turna, Grygoriy Ursol, Jaroslav Vanasek, Mirta Varela, Marcela Vallejo, Luis Vera, Ana-Paula Victorino, Tomas Vlasek, Ihor Vynnychenko, Buhai Wang, Jie Wang, Kai Wang, Yilong Wu, Kazuhiko Yamada, Chih-Hsin Yang, Takuma Yokoyama, Toshihide Yokoyama, Hiroshige Yoshioka, Fulden Yumuk, Angela Zambrano, Juan Jose Zarba, Oleg Zarubenkov, Marius Zemaitis, Li Zhang, Xin Zhang, Jun Zhao, Caicun Zhou, Jianying Zhou, Qing Zhou, and Alfred Zippelius

Subjects
medicine.medical_specialty, Chemotherapy, education.field_of_study, Performance status, business.industry, medicine.medical_treatment, Hazard ratio, Population, Phases of clinical research, General Medicine, Pembrolizumab, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, 030212 general & internal medicine, business, Lung cancer, education
Abstract

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

Published
2019
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11. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial

Author

Kohei Shitara, Mustafa Özgüroğlu, Yung-Jue Bang, Maria Di Bartolomeo, Mario Mandalà, Min-Hee Ryu, Lorenzo Fornaro, Tomasz Olesiński, Christian Caglevic, Hyun C Chung, Kei Muro, Eray Goekkurt, Wasat Mansoor, Raymond S McDermott, Einat Shacham-Shmueli, Xinqun Chen, Carlos Mayo, S Peter Kang, Atsushi Ohtsu, Charles S Fuchs, Guillermo Lerzo, Juan Manuel O'Connor, Guillermo Ariel Mendez, James Lynam, Niall Tebbutt, Mark Wong, Andrew Strickland, Chris Karapetis, David Goldstein, Paul Vasey, Jean-Luc Van Laethem, Eric Van Cutsem, Scott Berry, Mark Vincent, Bettina Muller, Felipe Rey, Angela Zambrano, Joaquin Guerra, Merete Krogh, Lene Baeksgaard, Mette Yilmaz, Anneli Elme, Andrus Magi, Paivi Auvinen, Tuomo Alanko, Markus Moehler, Volker Kunzmann, Thomas Seufferlein, Peter Thuss-Patience, Thomas Hoehler, Georg Haag, Salah-Eddin Al-Batran, Hugo Castro, Karla Lopez, Mynor Aguilar Vasquez, Mario Sandoval, Ka On Lam, Sinead Cuffe, Cathy Kelly, Ravit Geva, Ayala Hubert, Alex Beny, Baruch Brenner, Aprile Giuseppe, Alfredo Falcone, Evaristo Maiello, Rodolfo Passalacqua, Vincenzo Montesarchio, Hiroki Hara, Keisho Chin, Tomohiro Nishina, Yoshito Komatsu, Nozumo Machida, Shuichi Hironaka, Taroh Satoh, Takao Tamura, Naotaoshi Sugimoto, Haruhiko Cho, Yashushi Omuro, Ken Kato, Masahiro Goto, Ichinosuke Hyodo, Kazuhiro Yoshida, Hideo Baba, Taito Esaki, Junji Furuse, Wan Zamaniah Wan Mohammed, Carlos Hernandez Hernandez, Juan Casas Garcia, Adriana Dominguez Andrade, Katriona Clarke, Geir Hjortland, Nils Glenjen, Tomasz Kubiatowski, Jassem Jacek, Marek Wojtukiewicz, Sergey Lazarev, Yuri Lancukhay, Sergey Afanasayev, Vladimir Moiseyenko, Vladimir Kostorov, Svetlana Protsenko, Vadim Shirinkin, Dina Sakaeva, Natalia Fadeeva, Wei Peng Yong, Chau Hsien Matthew Ng, Barbara Robertson, Bernardo Rapaport, Graham Cohen, Lydia Dreosti, Paul Ruff, Conrad Jacobs, Gregory Landers, Waldemar Szpak, Sang-Young Roh, Jeeyun Lee, Yeul Hong Kim, Hyun Cheol Chung, Maria Alsina Maqueda, Federico Longo Munoz, Andres Cervantes Aguilar, Enrique Aranda Aguilar, Pilar Garcia Alfonso, Fernando Rivera, Jaime Feliu Batle, Roberto Pazo Cid, Kun-Huei Yeh, Jen-Shi Chen, Yee Chao, Chia-Jui Yen, Oguz Kara, Suayib Yalcin, Daniel Hochhauser, Ian Chau, Al Benson, Veena Shankaran, Walid Shaib, Philip Philip, Vivek Sharma, Robert Siegel, Weijing Sun, Zev Wainberg, Ben George, Andrea Bullock, Samuel Myrick, Josephine Faruol, Richard Siegel, Timothy Larson, Carlos Becerra, Suresh Ratnam, Donald A. Richards, and Stephen L. Riche

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Esophageal Neoplasms, Paclitaxel, medicine.medical_treatment, Population, Phases of clinical research, Pembrolizumab, Adenocarcinoma, Antibodies, Monoclonal, Humanized, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, medicine, Humans, Infusions, Intravenous, education, Survival rate, Aged, Neoplasm Staging, education.field_of_study, Chemotherapy, business.industry, Hazard ratio, Cancer, General Medicine, Middle Aged, medicine.disease, Survival Rate, Treatment Outcome, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Female, Esophagogastric Junction, business
Abstract

Summary Background Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Methods This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. Eligible patients were randomised (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel. Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher. Safety was assessed in all patients, irrespective of CPS. The significance threshold for overall survival was p=0·0135 (one-sided). This trial is registered at ClinicalTrials.gov, number NCT02370498. Findings Between June 4, 2015, and July 26, 2016, 592 patients were enrolled. Of the 395 patients who had a PD-L1 CPS of 1 or higher, 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel. As of Oct 26, 2017, 326 patients in the population with CPS of 1 or higher had died (151 [77%] of 196 patients in the pembrolizumab group and 175 [88%] of 199 patients in the paclitaxel group). Median overall survival was 9·1 months (95% CI 6·2–10·7) with pembrolizumab and 8·3 months (7·6–9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66–1·03; one-sided p=0·0421). Median progression-free survival was 1·5 months (95% CI 1·4–2·0) with pembrolizumab and 4·1 months (3·1–4·2) with paclitaxel (HR 1·27, 95% CI 1·03–1·57). In the total population, grade 3–5 treatment-related adverse events occurred in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel. Interpretation Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher. Pembrolizumab had a better safety profile than paclitaxel. Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing. Funding Merck Sharp & Dohme, a subsidiary of Merck & Co.

Published
2018
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