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Background Given rising cancer drug costs, US Medicare recently proposed to tie some drug prices to average prices paid by comparable countries. To understand the potential scope of this policy, we assessed differences in cancer drug prices in the US and European countries. We also evaluated the correlation between drug prices and their clinical benefit, as measured by two value frameworks: the American Society of Clinical Oncology Value Framework v2 (ASCO VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale v1.1 (ESMO-MCBS). Methods We identified all new drugs for adult solid and hematologic cancers, approved by the FDA from 2009-2017 and that have also been approved by the EMA by December 31, 2018. US average sales prices (and if not available, wholesale acquisition costs) were extracted as of February 1, 2019, and compared to comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland. ASCO VF and ESMO-MCBS scores were assessed for pivotal trials supporting solid tumor drugs; in case of multiple trials, we focused on the highest score. Consistent with the developers of the rating scales, “high benefit” was defined as scores of A-B (neo/adjuvant setting) and 4-5 (palliative setting) on the ESMO-MCBS scale and scores ≥45 on the ASCO VF. Linear regression models and non-parametric Kruskal-Wallis test and were used to assess the association between drug prices and benefit scores. Results The study cohort included 63 drugs approved by the FDA and the EMA during the study period. 46 (73%) were approved for solid tumors, and 17 (27%) were approved for hematologic malignancies. Overall, median cancer drug prices in Europe were 52% (interquartile range: 37-72%) lower than US prices. There was no association between monthly treatment cost and ASCO-VF or ESMO-MCBS scores in any country. There was also no association between price differential between US and median European drug prices and either ASCO-VF (P = 0.599) or ESMO-MBCS (P = 0.321) scores. Conclusions Drug prices of cancer drugs were not associated with clinical benefit in the US or in European countries. Cancer drug prices in the US were significantly higher than in the compared European countries. Legal entity responsible for the study University of Zurich. Funding Swiss Cancer League. Disclosure All authors have declared no conflicts of interest.

Background Clinical trials supporting approval for new drugs often evaluate surrogate endpoints, and data on meaningful outcomes like OS or QoL may not be available. Here, we evaluated changes in the magnitude of clinical benefit, OS and QoL after approval. Methods We examined data on pivotal trials supporting FDA accelerated (AA) and regular (RA) cancer drug approvals between January 2006, and December 2015. For AA drugs, if conversion to RA was granted, only the confirmatory trial was analysed. To determine any new evidence on OS and QoL in the postmarketing period (PMP) we performed a systematic search of Pubmed and ClinicalTrials.gov. European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) grades were applied for trials at approval and in the PMP. Substantial clinical benefit was defined as a grade of A or B for trials of curative intent and 4 or 5 for those of palliative intent. Results We identified 96 pivotal trials supporting the approval of 47 drugs for 94 solid tumour indications. Of these indications, 22 (23%) were granted AA and 21 (22%) were converted to RA. At time of approval, 45 (48%) trials showed improved OS, 15 (16%) improved QoL and 33 (34%) had substantial clinical benefit. With a median PMP of 3.7 years, 50 (52%) trials reported OS data and 27 (28%) on QoL. Of these, 48 could be graded by the ESMO-MCBS. Of the updated 51 trials approved based on surrogate endpoints, only 7 (14%) showed an improvement in OS. In advanced disease, out of 74 trials for which there was no evidence on QoL at the time of approval, 12 (16%) showed improved QoL subsequently. Updated results led to changes in clinical benefit in 11 trials (10 upgrades, 1 downgrade) with 30 (62%) showing substantial clinical benefit. Among all trials, 52 (54%) showed improved OS, 27 (28%) improved QoL and 42 (44%) met the threshold for substantial clinical benefit. Conclusions After 3.7 years of post-marketing time, 54% of FDA approved cancer drugs showed statistically significant improvement in OS and 28% in QoL. Less than a half of trials supporting FDA approval met the threshold for substantial clinical benefit using ESMO-MCBS. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure E. Amir: Speaker Bureau / Expert testimony: Genentech/Roche; Advisory / Consultancy: Apobiologix; Advisory / Consultancy: Agendia; Advisory / Consultancy: Myriad Genetics. All other authors have declared no conflicts of interest.