Yannis Metaxas1, Gareth Rivalland2, Laetitia A Mauti3, Dirk Klingbiel4, Steven Kao5, Sabine Schmid6, Anna K Nowak7, Oliver Gautschi8, Tammo Bartnick9, Brett G Hughes10, Hasna Bouchaab11, Sacha I Rothschild12, Nick Pavlakis13, Sibylle Wolleb14, Ulf Petrausch15, Kenneth O'Byrne16, Patrizia Froesch17, Melanie Löffler-Baumann18, Susanne Pratsch-Peter19, Prudence Russell20, Walter Mingrone21, Spasenija Savic22, Bibhusal Thapa2, Martin Früh6, Miklos Pless3, Roger von Moos1, Thomas John23. 1. Department of Medical Oncology, Cantonal Hospital Grison, Chur, Switzerland. 2. Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia. 3. Department of Medical Oncology, Cantonal Hospital Winterthur, Winterthur, Switzerland. 4. Swiss Group for Clinical Cancer Research Coordinating Center, University of Bern, Bern, Switzerland. 5. Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 6. Department of Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, University of Bern, Switzerland. 7. University of Western Australia, Crawley, Western Australia, Australia; Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. 8. Department of Medical Oncology, Lucerne Cantonal Hospital, Lucerne, Switzerland. 9. Department of Medical Oncology, Cantonal Hospital Baden, Baden, Switzerland. 10. Cancer Care Services, The Royal Brisbane and Women's Hospital, Queensland, Australia. 11. Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. 12. Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. 13. Department of Medical Oncology, Royal North Shore Hospital, Sydney University, Sydney, New South Wales, Australia. 14. Department of Medical Oncology, Uster Hospital, Uster, Switzerland. 15. Department of Medical Oncology, Oncological Center Zurich, Zurich, Switzerland. 16. Princess Alexandra Hospital, Brisbane, Queensland, Australia; Queensland University of Technology, Brisbane, Queensland, Australia. 17. Department of Oncology, Cantonal Hospital, Bellinzona, Switzerland. 18. Department of Oncology, Hospital St. Clara, Basel, Switzerland. 19. Department of Medical Oncology, City Hospital Waid, Zurich, Switzerland. 20. Department of Pathology, St. Vincent's Hospital, Fitzroy, Victoria, Australia. 21. Department of Medical Oncology, Solothurn Hospitals, Olten, Switzerland. 22. Department of Pathology, University Hospital Basel, Basel, Switzerland. 23. Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia. Electronic address: tom.john@onjcri.org.au.
Abstract
INTRODUCTION: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). METHODS: Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%). RESULTS: A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. CONCLUSION: These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti-PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.
INTRODUCTION: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). METHODS: Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%). RESULTS: A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. CONCLUSION: These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti-PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.
Authors: Michele Carbone; Prasad S Adusumilli; H Richard Alexander; Paul Baas; Fabrizio Bardelli; Angela Bononi; Raphael Bueno; Emanuela Felley-Bosco; Francoise Galateau-Salle; David Jablons; Aaron S Mansfield; Michael Minaai; Marc de Perrot; Patricia Pesavento; Valerie Rusch; David T Severson; Emanuela Taioli; Anne Tsao; Gavitt Woodard; Haining Yang; Marjorie G Zauderer; Harvey I Pass Journal: CA Cancer J Clin Date: 2019-07-08 Impact factor: 508.702
Authors: Hee-Jin Jang; Cynthia Y Truong; Eric M Lo; Hudson M Holmes; Daniela Ramos; Maheshwari Ramineni; Ju-Seog Lee; Daniel Y Wang; Massimo Pietropaolo; R Taylor Ripley; Bryan M Burt; Hyun-Sung Lee Journal: Ann Thorac Surg Date: 2021-09-27 Impact factor: 4.330
Authors: Oscar Arrieta; Andrés F Cardona; Luis Lara-Mejía; David Heredia; Feliciano Barrón; Zyanya Lucia Zatarain-Barrón; Francisco Lozano; Vladmir Cordeiro de Lima; Federico Maldonado; Francisco Corona-Cruz; Maritza Ramos; Luis Cabrera; Claudio Martin; Luis Corrales; Mauricio Cuello; Marisol Arroyo-Hernández; Enrique Aman; Ludwing Bacon; Renata Baez; Sergio Benitez; Antonio Botero; Mauricio Burotto; Christian Caglevic; Gustavo Ferraris; Helano Freitas; Diego Lucas Kaen; Sebastián Lamot; Gustavo Lyons; Luis Mas; Andrea Mata; Clarissa Mathias; Alvaro Muñoz; Ana Karina Patane; George Oblitas; Luis Pino; Luis E Raez; Jordi Remon; Leonardo Rojas; Christian Rolfo; Alejandro Ruiz-Patiño; Suraj Samtani; Lucia Viola; Santiago Viteri; Rafael Rosell Journal: Crit Rev Oncol Hematol Date: 2020-06-20 Impact factor: 6.312
Authors: Luca Cantini; Robert A Belderbos; Cornedine J Gooijer; Daphne W Dumoulin; Robin Cornelissen; Sara Baart; Jacobus A Burgers; Paul Baas; Joachim G J V Aerts Journal: Transl Lung Cancer Res Date: 2020-08