Abstract
Progression-free survival (PFS) and overall survival (OS) are two common endpoints in cancer trials. OS is usually preferred, because it is reliable, precise, meaningful, and can easily be documented. However, subsequent lines of therapy might confound the effects of first-line treatment on OS. Whether PFS or OS is the more appropriate endpoint in clinical trials of metastatic cancer remains controversial. Previous reports on lung cancer have shown that an increase in PFS does not necessarily result in an increase in OS; however, post-progression survival (PPS) is strongly associated with OS after early-line treatment. The significance of PPS after first and second-line therapy at the individual level in patients with advanced lung cancer has also recently been reported. Findings of previous reports indicate that PPS is highly associated with OS after first and second-line chemotherapy in patients with advanced non-small cell lung cancer and small cell lung cancer, whereas PFS is only moderately associated with OS. Therefore, subsequent treatment after disease progression following early-line treatments may greatly influence OS. This review demonstrates that even in advanced lung cancer, PPS, rather than PFS, has become more strongly associated with OS over the years, potentially because of intensive post-study treatments. As a result of the increasing impact of PPS on OS, a PFS-related advantage does not necessarily indicate an OS-related advantage. Thus, the prolongation of PPS might limit the classical role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials.