Sasha Thomson1, Noah Witzke1, Bishal Gyawali2, Seanthel Delos Santos1, Suji Udayakumar1, Claudia Cardone3, Matthew C Cheung4, Kelvin K W Chan5. 1. Evaluative Clinical Sciences, Odette Cancer Centre Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada. 2. Department of Oncology, Department of Public Health Sciences and Division of Cancer Care and Epidemiology, Queen's University, Kingston, Ontario, Canada. 3. Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italy. 4. Evaluative Clinical Sciences, Odette Cancer Centre Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 5. Evaluative Clinical Sciences, Odette Cancer Centre Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada. Electronic address: kelvin.chan@sunnybrook.ca.
Abstract
BACKGROUND: Increasingly, cancer drugs are being approved based on surrogate measurements of efficacy. Clinically meaningful data, such as overall survival (OS) and quality of life, are often only presented in subsequent publications. We examined if the clinical benefit of cancer drugs, as measured by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), improves post-European Medicines Agency (EMA) approval as more data emerges. METHODS: Cancer drug indications approved by the EMA from January 2006 to December 2016 were reviewed and trials cited for efficacy were identified. Primary and subsequent publications (up to December 2019) of scorable trials were included. Changes in benefit over time were measured using ESMO-MCBS thresholds for non-curative (≥4 for substantial, =3 for intermediate and ≤2 for low benefit) and curative intent (A or B for major benefit) scoring. RESULTS: Fifty-five non-curative and two curative intent trials were included. At approval, 29.1% of non-curative trials were substantial, 45.5% intermediate and 25.5% low benefit. For curative intent trials, one displayed major benefit and one displayed no major benefit. We identified 82 subsequent publications for reassessment. A change in ESMO-MCBS classification was seen in 34.5% of non-curative trials (11 raised and 8 lowered). At 3-year reassessment, 36.4% of non-curative trials were substantial, 34.5% intermediate and 29.1% low benefit. Both curative trials showed no major benefit at reassessment. CONCLUSION: As over a third of trials changed classification, in either direction, reassessing the ESMO-MCBS score of approved cancer drugs may help to inform patients and ensure ongoing relevance of regulatory and reimbursement decisions.
BACKGROUND: Increasingly, cancer drugs are being approved based on surrogate measurements of efficacy. Clinically meaningful data, such as overall survival (OS) and quality of life, are often only presented in subsequent publications. We examined if the clinical benefit of cancer drugs, as measured by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), improves post-European Medicines Agency (EMA) approval as more data emerges. METHODS:Cancer drug indications approved by the EMA from January 2006 to December 2016 were reviewed and trials cited for efficacy were identified. Primary and subsequent publications (up to December 2019) of scorable trials were included. Changes in benefit over time were measured using ESMO-MCBS thresholds for non-curative (≥4 for substantial, =3 for intermediate and ≤2 for low benefit) and curative intent (A or B for major benefit) scoring. RESULTS: Fifty-five non-curative and two curative intent trials were included. At approval, 29.1% of non-curative trials were substantial, 45.5% intermediate and 25.5% low benefit. For curative intent trials, one displayed major benefit and one displayed no major benefit. We identified 82 subsequent publications for reassessment. A change in ESMO-MCBS classification was seen in 34.5% of non-curative trials (11 raised and 8 lowered). At 3-year reassessment, 36.4% of non-curative trials were substantial, 34.5% intermediate and 29.1% low benefit. Both curative trials showed no major benefit at reassessment. CONCLUSION: As over a third of trials changed classification, in either direction, reassessing the ESMO-MCBS score of approved cancer drugs may help to inform patients and ensure ongoing relevance of regulatory and reimbursement decisions.