Associations With Definitive Outcomes and Clinical Benefit of Cancer Drugs at the Time of Marketing Approval and in the Postmarketing Period

Authors:
Aida Bujosa Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, and Departament de Medicina de la Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain;

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Consolación Moltó Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, and Departament de Medicina de la Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain;

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Thomas J. Hwang Program on Regulation, Therapeutics, and Law, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts;

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José Carlos Tapia Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, and Departament de Medicina de la Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain;

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Kerstin N. Vokinger Institute for Primary Care and Health Outcomes Research, University of Zürich, Zürich, Switzerland;

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Arnoud J. Templeton Department of Medical Oncology, St. Claraspital Basel, and Faculty of Medicine, University of Basel, Basel, Switzerland;

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Ignasi Gich Department of Epidemiology, Hospital de la Santa Creu i Sant Pau, and Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; and

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Agustí Barnadas Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, and Departament de Medicina de la Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain;

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Eitan Amir Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, and the University of Toronto, Toronto, Ontario, Canada.

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Ariadna Tibau Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, and Departament de Medicina de la Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain;

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Background: Most anticancer drugs are approved by regulatory agencies based on surrogate measures. This article explores the variables associated with overall survival (OS), quality of life (QoL), and substantial clinical benefit among anticancer drugs at the time of approval and in the postmarketing period. Methods: Anticancer drugs approved by the FDA between January 2006 and December 2015 and with postmarketing follow-up until April 2019 were identified. We evaluated trial-level data supporting approval and any updated OS and/or QoL data. We applied the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the ASCO Value Framework (ASCO-VF) to initial and follow-up studies. Results: We found that 58 drugs were approved for 96 indications based on 96 trials. At registration, approval was based on improved OS in 39 trials (41%) and improved QoL in 16 of 45 indications (36%). Postmarketing data showed an improvement in OS for 28 of 59 trials (47%) and in QoL for 22 of 48 indications (46%). At the time of approval, 25 of 94 (27%) and 26 of 80 scorable trials (33%) met substantial benefit thresholds using the ESMO-MCBS and ASCO-VF, respectively. In the postmarketing period, 37 of 69 (54%) and 35 of 65 (54%) trials met the substantial benefit thresholds. Drugs with companion diagnostics and immune checkpoint inhibitors were associated significantly with substantial clinical benefit. Conclusions: Compared with the time of approval, more anticancer drugs showed improved OS and QoL and met the ESMO-MCBS or ASCO-VF thresholds for substantial benefit over the course of postmarketing time. However, only approximately half of the trials met the threshold for substantial benefit. Companion diagnostic drugs and immunotherapy seemed to be associated with greater clinical benefit.

Submitted November 1, 2020; final revision received January 7, 2021; accepted for publication January 7, 2021.

Published online September 24, 2021.

Previous presentation: Presented at the 2020 ASCO Annual Meeting; May 29–31, 2020. Abstract 7052. doi, 10.1200/JCO.2020.38.15_suppl.7052

Author contributions: Formal analysis: Bujosa, Gich, Tibau. Methodology: Bujosa, Molto, Tapia, Tibau. Supervision: Amir, Tibau. Writing – original draft: Bujosa, Tibau. Writing – review and editing: Molto, Hwang, Tapia, Vokinger, Templeton, Gich, Barnadas, Amir.

Disclosures: Dr. Bujosa has disclosed receiving a travel grant from Roche. Dr. Tapia has disclosed receiving travel grants from Roche and Grünenthal Group. Dr. Templeton has disclosed receiving travel grants from Janssen, Sanofi, Ipsen, and Roche, and honoraria from Astellas. Dr. Barnadas has disclosed receiving travel grants from Pfizer and Roche, and honoraria from Novartis, Pfizer, and Lilly. Dr. Amir has disclosed providing expert testimony for Genentech/Roche and serving as a consultant for Sandoz, Apobiologix, Agendia, and Myriad Genetics. Dr. Tibau has disclosed receiving a travel grant from Roche, Ipsen, Pfizer, and Lilly, and honoraria from Eisai. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Ariadna Tibau, MD, PhD, Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau, and Universitat Autònoma de Barcelona, Carrer Mas Casanovas, 90, 08041 Barcelona, Catalonia, Spain. Email: ATibau@santpau.cat

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