Surrogate endpoints in immunotherapy trials for solid tumors

Fausto Petrelli, Michele Ghidini, Antonio Costanzo, Valentina Rampulla, Antonio Varricchio, Gianluca Tomasello


In a systematic review published in European Journal of Cancer, Nie et al. analyzed the role of objective response (ORR), disease control and progression-free survival (PFS) as surrogate endpoints in phase II and III studies with immunotherapy [anti-PD(L)1 agents] in solid tumors (1). As expected, across 43 trials available for inclusion, no surrogate endpoint was validated using standard statistical criteria, because neither RECIST-based ORR, nor PFS were able to capture the final overall survival (OS) gain used generally for authority approval. As stated by authors, anti-PD-1/PD-L1 drugs may induce an initial increase in the tumor volume, and the delayed antitumor activity can, thereafter, produce a late shrinkage of the tumor volume. This may cause pseudo-progression and explains why ORR and PFS correlate weakly with survival.