It is unknown to what extent cancer drugs approved in Switzerland by Swissmedic fulfil criteria of clinical benefit according to ESMO, ASCO and the Swiss OLUtool criteria.
An electronic search of studies that led to new marketing authorisations in Switzerland between 2010 and 2019 was performed. Studies were evaluated according ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.1, ASCO-Value Framework v2 (ASCO-VF) and OLUtool v2. Substantial benefit for ESMO-MCBS, was defined as a grade A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. For ASCO-VF and OLUtool clinical benefit was defined as score >45 and A or B, respectively. Correlation between the frameworks was calculated with Cohen’s Kappa (κ). Factors associated with clinical benefit were evaluated by logistic regression. All statistical tests were two-sided.
In the study period, 48 cancer drugs were approved for 92 evaluable indications, based on 100 studies. Of all studies 93% were in the palliative setting and 81% were phase III studies. Ratings for ESMO-MCBS, ASCO-VF and OLUtool could be performed for 100, 86, and 97 studies, respectively. Overall, 39 (39%), 44 (51%), 45 (46%) of the studies showed substantial clinical benefit according to ESMO-MCBS, ASCO-VF, OLUtool criteria, respectively. There was fair concordance between ESMO-MCBS and ASCO-VF in the palliative setting (κ = 0.31, p=0.004) and moderate concordance between ESMO-MCBS and OLUtool (κ = 0.41, p<0.001). There was no concordance between ASCO-VF and OLUtool (κ = 0.18, p=0.12). Factors associated with clinical benefit in the palliative setting in multivariable analysis are shown in the table. Table: 1583O
|ESMO-MCBS 1.1||Breast cancer (vs. lung cancer) Melanoma (vs. lung cancer)||0.21 (0.093) 0.21 (0.073)|
|ASCO-VF v2*||CPI combination tx (vs. small molecule) Chemo mono tx (vs. small molecule) CDK4/6 inhibitor plus endocrine tx (vs. small molecule)||0.08 (0.028) 0.13 (0.093) 0.06 (0.017)|
|OLUtool v2.0||Blinded study (vs. open label) Phase III study (vs. phase I or II)||3.30 (0.012) 3.47 (0.080)|
CPI, checkpoint inhibitor; OR, odds ratio (adjusted); tx, therapy.* no adjustments were made since no other covariates had a p-value <0.1 in univariable analysis.
Only around half of the trials supporting marketing authorisation of recently approved cancer drugs in Switzerland meet the criteria for substantial clinical benefit when evaluated with ESMO-MCBS, ASCO-VF or OLUtool. At best, there was only moderate concordance between the grading systems.
Clinical trial identification
Legal entity responsible for the study
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All authors have declared no conflicts of interest.