5 Endpoints for Rare Oncology Trials

In general, greater certainty about the clinical benefit of a drug correlates with an increased time to achieve needed results — the best evidence can take years of careful follow-up. But an unnecessarily long time to market isn’t good for sponsors and patients alike. This is especially true for patients battling rare cancers: With many of these conditions lacking standard treatments, these patients often don’t have the time to wait for more concrete measures. In these cases, choosing the appropriate endpoint for a trial is crucial.

Read on for a rundown of the five major types of clinical endpoints in rare oncology and the best way to use them.

1. Overall Survival Rates

Overall survival rates are the gold standard endpoint for cancer trials. They are an unambiguous, binary endpoint that is universally accepted as a direct measurement of benefit. Overall survival rates measure the time from randomization to death by any cause. This requires a prospective, controlled, randomized study.

While overall survival rates may yield the most clinically relevant data, they aren’t always feasible for drug trials, especially when dealing with rare cancers. Because achieving mature data may require prolonged follow-up, it can take years to gather enough information for traditional approval. Despite these drawbacks, overall survival is still a useful endpoint in some cases, such as later confirmatory studies.

2. Event-Free Survival

The FDA defines event-free survival as the length of time between when a primary cancer treatment ends and the patient does not experience certain complications. What these complications are must be clearly defined by study protocol and can include such “events” as the return of the cancer or the onset of specific symptoms. Event-free survival endpoints can include tumor or symptomatic assessments.

3. Tumor Assessments

As the name suggests, this group of endpoints is largely dependent on tumor progression, remission, and/or recurrence. The umbrella of tumor assessments covers multiple specific surrogate endpoints, including progression-free survival, objective response rate, time to progression, disease-free survival, and time to treatment failure. Target lesions must be determined at baseline — not retroactively.

Using tumor assessments as a surrogate endpoint requires an evaluation of potential bias or uncertainty, which is best verified by independent central reviewers blinded to study treatments. This measure prevents introducing local bias from investigator or sponsor staff.

4. Symptomatic Assessments

Because of the delay between tumor progression and the onset of cancer symptoms, as well as the harsh nature of most existing treatments, symptomatic assessments can be difficult to designate as a surrogate endpoint. However, they are sometimes useful in rare oncology. Examples of symptomatic assessments include spleen size, weight gain, or time to symptom resolution.

Global health-related quality of life assessments are not suitable as primary endpoints in oncology, as differences could be attributed to a favorable safety profile rather than actual efficacy. For this reason, the FDA specifies that it must be able to distinguish between improvement in tumor symptoms and a lack of drug toxicity. However, quality of life assessments can be used to provide quality control to survival endpoints.

5. Biomarkers

Pharmacodynamic biomarkers are generally used to guide drug development rather than gain regulatory approval. Biomarkers are being used more and more often to enroll patients, identifying individuals who can benefit the most from a particular treatment. Such markers are an important aspect of study enrichment, but very few actually have clinical utility. While not usually used as primary endpoints in oncology, these measurements can be part of a composite endpoint.

Other Accelerated Approval Strategies

Using alternative endpoints isn’t the only way to gain quicker regulatory approval for rare cancer treatments. From special approval pathways to adaptive study design, our rare oncology webinar explores methods of expediting drug development.