Most new oncology therapies are studied in the advanced/metastatic setting. However, there is an increasing focus on earlier stage disease. Nevertheless, measuring Overall Survival (OS) in neo-/adjuvant therapy trials can be very challenging due to the increased life expectancy and the confounding effects of subsequent treatments. Thus, their primary endpoints tend to be surrogate survival metrics (e.g. metastases-free survival). This research aims evaluates the health technology assessment (HTA) acceptability of such endpoints through recent neo-/adjuvant HTA assessments.

The European Medicines Agency (EMA) website was screened for any neo-/adjuvant oncology therapies approved (1 January 2013-22 October 2018) and any corresponding publicly-available assessments by HTA bodies (NICE, SMC, IQWiG, G-BA, CADTH, PBAC, HAS) were identified and key data extracted.

Six neo-/adjuvant therapies have received marketing authorization by the European Commission (EC). These six have been on the market for an average of 8.9 months (range: 0.9-39.3 months, median: 3.3 months). In four of the six, the pivotal trial primary endpoints were measures of relapse-/disease-free survival, (others: pathological complete response and PFS/OS co-primary). Only one had mature OS data available at EC-approval. Four of the six therapies had received at least draft guidance by an HTA body, encompassing 11 HTA assessments in total (4: NICE, 2: IQWiG, HAS; 1: SMC, CADTH, G-BA). Only two of 11 (18%) were positive outcomes (both NICE), the remaining nine were negative.

Oncology therapies are increasingly receiving regulatory approval in the neo-/adjuvant setting. However, their pivotal trials are frequently powered to show benefits in disease-/metastases-free survival. Whilst sufficient for regulatory approval, translating this to favorable HTA decisions has been more challenging. Clearly establishing linkages between surrogate survival metrics and OS alongside measuring metrics that clearly portray patient benefits (e.g. time to symptomatic progression) could improve HTA-acceptability. Further, some payers allow for temporary reimbursement whilst additional evidence is generated (e.g. Cancer Drugs Fund in England).