A new approach to evaluating the value and efficacy of treatment was developed by associate professor Meredith Regan ScD of Harvard’s Medical School and Dana Farber Institute.
A recent article published in Medical Express quotes Dr. Regan as saying that the current measurements used to determine the efficacy of a treatment leave room for improvement. This is especially true in the evaluation of immuno-oncology-based regimens.
The measurements, or endpoints, are defined as the end results of a clinical trial. They must be measured objectively in order to determine whether the investigational drug will be beneficial.
Dr. Regan and her team proposed that in the future, treatment-free survival (TFS) should include the quality of survival time. She emphasized that the addition would provide more informed decisions. According to Dr. Regan, TFS represents the time between ending the protocol-assigned therapy, starting a subsequent therapy, or death.
The authors’ goal is to not only improve survival time but to focus on the well-being of the patient during survival.
The next step for the team is to apply TFS analysis to previous clinical trials to conform with standard endpoints and incorporate the new endpoint in future trials.
About the CheckMate 214 Phase 3 Clinical Trial
The CheckMate Clinical Trial began in October 2014 at 175 sites in 28 countries. The trial involved the study of nivolumab (Opdivo) combined with ipilimumab (Yervoy) (n550).
Nivolumab is a PD-1 checkpoint inhibitor that is approved to treat renal-cell carcinoma. Whereas ipilimumab is an antibody approved to treat metastatic melanoma. Ipilimumab was associated with a favorable response rate but showed substantial toxicity in a trial of patients with renal-cell carcinoma. It was not until it was paired with Opdivo that Yervoy showed promising efficacy in various tumor types.
The duo was compared against the targeted, standard monotherapy sunitinib (Sutent) (n546). Sutent is a vascular endothelial growth factor receptor tyrosine kinase inhibitor. The drug has been the standard of care for first-line treatment of advanced renal-cell carcinoma.
The cohort consisted of 1096 patients with advanced untreated renal cell carcinoma who had not received prior treatment. A total of 847 patients in this group were evaluated as poor or intermediate risks.
The primary completion date was February 2016. The entire study will conclude in January of 2023.
About Preliminary Results
Dr. Regan noted that when a treatment is developed, it presents an opportunity to improve the toxicity and efficacy for the patients. That is when new endpoints are needed.
Monitoring trial participants for TFS entailed calculating the days patients had either moderate or severe adverse events that were related to their treatment.
Calculating treatment with the checkpoint inhibitor combination (Opdivo and Yervoy) over a 42-month time frame found that the combination provided almost two times longer TFS than the monotherapy, Sutent. Among patients with favorable risk, the TFS for the combination was almost three times that of the monotherapy.
At this juncture, a total of 52 percent and 39 percent of patients in the study were alive having been treated with the combination and monotherapy respectively.
Although the OS was almost identical for patients with favorable risk over the same 42 month period, the TFS was significantly different. For example, 20 percent of participants who were administered the combination were treatment-free against 9 percent of patients receiving monotherapy.
Results also showed that the patients being treated with Sutent spent more time than their counterparts receiving therapy and a longer time experiencing treatment-related adverse events.
Looking Forward
Dr. Regan explained that the positive results of CheckMate show that the researchers have developed an improved method of assessing the value of new treatments when conducting clinical trials.
But Dr. Regan acknowledged that there are limitations as they continue to refine how they evaluate toxicity. Even though the team registered the severity of the toxicity, they were unable to record the number of such events that happened in one day or the type of adverse event.
And lastly, attempting to collect data after the patients end the assigned protocol appears challenging.
