Endpoints in cancer clinical trials

Abstract

Endpoints are measurable clinical and biological findings that are used for the development and assessment of treatment options. In the treatment of cancer, endpoints can be classified into two categories: "patient-centered clinical endpoints" including overall survival (OS) and health-related quality of life (QoL), and "tumor-centered clinical endpoints" such as progression-free survival. Surrogate endpoints are tumor-centered clinical endpoints that can be used as substitutes for patient-centered clinical endpoints, particularly OS. The choice of endpoints in oncology trials is a major problem. The published Consolidated Standards of Reporting Trials (CONSORT) best-practice guidelines encourage the reporting of clearly defined primary and secondary outcome measures. OS is the gold standard of endpoints but as increasing numbers of effective salvage treatments become available for many types of cancer, much larger numbers of patients are included; this requires a longer follow-up period and increases the cost of clinical trials. Thus, tumor-centered clinical endpoints that can be assessed earlier and used as surrogates for overall survival are increasingly studied, but most of them currently lack standardized definitions to enable cross comparison of results among different clinical trials and they have not been validated as surrogate endpoints. In addition, the variability of their definition can strongly impact the trial's conclusions by affecting both statistical power and estimation. In this context, QoL constitutes an available and useful surrogate endpoint for trials to ensure treatment benefit from both the patient and public health points of view. Methodological research should be pursued to develop standard outcome definitions for use in cancer clinical trials and to define a standardized longitudinal analysis of QoL data.

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

“…The correlation between objective response rate (ORR), time to progression, disease-free survival, or progressionfree survival (PFS) and OS is poorly understood [76,79]. Some studies investigating ICBs in NSCLC, RCC, HNSCC, and UC have demonstrated increased OS in the absence of a PFS benefit [27,28,31,42,47,57], whereas other trials in melanoma and NSCLC have demonstrated increased OS, as well as ORR and PFS, compared with standard of care (Table 2) [23,43].…”

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“…whether to exclude the primary site by means of specifically recording regional control (RC). Despite the published Consolidated Standards of Reporting Trials (CONSORT) best practice guidelines, to date there is no common agreement on this term [33,34].…”

“…The difference to PFS is that TTP does not include deaths. It may only be used when the event of interest is solely disease progression, and investigators have to be aware of the fact that TTP does differ from PFS in this very aspect [34]. Unfortunately, TTP and PFS are still frequently used interchangeable by investigators [27].…”

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“…A member of the medical team administered the two QoL questionnaires to the patient. Our methodology for QoL questionnaire administration complied with the users' guide of the two questionnaires [2,12]. Indeed, for QUAL-E, it was necessarily a member of the medical team who interviewed and recorded the patient's responses.…”

“…Equivalence or non-inferiority trials to control for toxicity and to assess deescalating doses are increasingly required. This is why taking into account another patientcentered outcome rather than tumor-centered endpoints seems a good alternative [2]. Health-related quality-of-life (HRQL) has become the second endpoint in clinical research in cancer to demonstrate clinical benefits of new treatments for patients [3].…”