‘Modest support’ for PFS as OS surrogate in HER2-positive metastatic breast cancer
medwireNews: Progression-free survival (PFS) only moderately correlates with overall survival (OS) at the individual and trial level in patients with HER2-positive metastatic breast cancer treated with HER2-targeted agents, say researchers.
They believe that the lack of a stronger correlation between PFS and OS for anti-HER2 agents in this patient population “could be related to the crossover that was allowed in several of the included trials, the administration of 2nd or [3rd]-line treatments and the relatively long post-progression time, a feature not common to the studies of other malignancies where PFS has been validated as surrogate for OS”.
This meta-analysis included individual patient data from 1839 HER2-positive patients enrolled in eight (six first-line) phase II or III randomised controlled trials assessing either trastuzumab or lapatinib, six of which assessed the agents as first-line treatments.
A total of 1462 patients experienced a PFS event while 1072 died from any cause during a median follow-up of 28 and 33 months, respectively. Median PFS was 5.7 months and median OS was 22.0 months.
PFS correlated moderately with OS at the individual patient level, with a Spearman coefficient of 0.67 corresponding to a squared correlation value of 0.45.
And at the trial level, the correlation between treatment effects on PFS and OS was also moderate, with a squared correlation value of 0.51, report Stefan Michiels (Institut Gustave Roussy, Villejuif, France) and colleagues.
“Thus only about half of the variation in weighted treatment effects on OS can be explained by effects on PFS”, write the study authors.
They note that there is no consensus on the minimum trial-level squared correlation value to validate a surrogate endpoint and cutoffs ranging from 0.60 to 0.75 have been used in previous studies.
However, Michiels et al say that “[n]o matter what cut-off is chosen, based on the current results we cannot accept PFS as validated surrogate for OS.”
And they conclude in the Annals of Oncology: “[T]he current findings provide only modest support for considering PFS as a surrogate for OS in HER2+ metastatic breast cancer; PFS does not completely substitute for OS in this setting.”
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016