No tumors at 30 months may be a good marker of progression-free survival (PFS) in clinical trials assessing first-line therapies for follicular lymphoma patients, according to new research.
Using a tumor-free — or complete-response — marker of progression-free survival may accelerate the development of novel therapies, making them available years before patients reach the progression-free stage, the researchers said.
“PFS is presently the principal endpoint for regulatory approval of new agents,” Qian Shi, PhD, and his colleagues at the department of health science research at the Mayo Clinic in Rochester, Minnesota, wrote. “However, advances in treatment and the indolent nature of follicular lymphoma challenge the use of PFS as the primary endpoint in clinical trials, where median PFS now approaches 6 to 8 years. Therefore, the identification of alternative endpoints that are measured earlier but can reliably predict PFS treatment effects is a critical need.”
Scientists categorize complete response as a surrogate endpoint in cancer because the actual endpoint is progression-free disease.
The study, “Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual Patient-Level Analysis of Multiple Randomized Trials,” was published in the Journal of Clinical Oncology.
Results from randomized trials have suggested that the treatments that generate the best PFS results have also produced higher complete-response rates, but variations in clinical trial design have made the data difficult to interpret.
The Follicular Lymphoma Analysis of Surrogate Hypothesis (FLASH) group did a study to determine whether a complete response by a certain timepoint could be used as a surrogate endpoint. The research covered randomized chemotherapy, immunotherapy, and chemoimmunotherapy trials of first-line therapy in follicular lymphoma.
The team chose complete response at 30 months as its principal surrogate-endpoint candidate. That is the time it takes to complete today’s standard treatment, including six months of initial, or induction, treatment and two years of maintenance therapy.
The team evaluated 13 randomized, multicenter clinical trials — eight induction and five maintenance — covering 3,837 evaluable patients. All were published after 1990.
The study found a strong correlation between complete response at 30 months and progression-free response: Patients with a complete response at 30 months were nearly 12 times more likely to remain progression-free and alive beyond a particular date.
“In conclusion, this pooled analysis of randomized chemotherapy, immunotherapy, or chemoimmunotherapy trials demonstrates that complete response at 30 months after initiation of induction treatment may serve as a surrogate end point for PFS in first-line follicular lymphoma treatment trials,” the researchers wrote.
The authors emphasized that their conclusion applied only to first-line follicular lymphoma trials. Future trials of complete response at 30 months should take into account the treatment used and disease population, they said.