Strategy for assessing new drug value in orphan diseases: An international case match control analysis of the PROPEL study

Background: Although randomized studies are designed to assess overall survival (OS) benefit, the conduct of regulatory studies in patients with orphan diseases can be timely and costly without offering the same commercial return on the investment. The peripheral T-cell lymphomas (PTCL) represent a rare group of heterogeneous lymphoid malignancies with very poor prognosis. PROPEL was a pivotal phase II study that led to the accelerated approval of pralatrexate for patients with relapsed or refractory PTCL. Methods: An international database of 859 patients was assembled from four institutions with an interest in PTCL, of which 386 were considered eligible for matching against the PROPEL criteria. Using a rigorous propensity score matching algorithm, a unique 1:1 case match of 80 patients was performed. Results: The analysis demonstrated an OS benefit for the PROPEL population with amedian OS of 4.07 and 15.24months (hazard ratio = 0.432, 95% confidence interval = 0.298 to 0.626), respectively, for the control and PROPEL populations. Highly statistically significant improvements in OS were noted for the PROPEL population about the subtype of PTCL (save anaplastic large cell lymphoma) and all age groups, including the elderly (>65 years of age). For patients on PROPEL, there was a statistically significant prolongation in progression free survival compared with the line of prior therapy, including those with refractory disease. Conclusion: In the context of this case-match-control study, patients treated on PROPEL experienced an OS advantage compared with an international database of historical controls. This information can help inform critical decision-making regarding clinical studies in PTCL.