Post-Progression Survival (PPS) and Overall Survival (OS) According to Treatment Type in Contemporary Phase III Trials in Advanced Breast Cancer (ABC).

Abstract

Abstract Objective: Progression-free survival (PFS) and time to tumor progression (TTP) have been the most frequent primary endpoints in recent phase III trials in ABC. OS, the most frequent secondary endpoint (Katz ASCO 2009), is largely influenced by subsequent-line therapy, and the role of PFS/TTP as surrogates for OS is still uncertain, perhaps due to the influence of post-progression therapy. Thus, PPS is of interest as a determinant of OS, and may vary according to treatment type.Methods: Using the medical subject headings “breast neoplasms” and “drug therapy”, we searched PubMed for phase III trials on systemic antineoplastic therapies published between January 1, 1998, and December 31, 2007 in one of 11 leading medical journals (Ann Oncol, BCRT, Br J Cancer, Cancer, Clin Cancer Res, Eur J Cancer, JCO, JNCI, Lancet Oncol, Lancet and NEJM). We excluded trials with factorial design, studies on high-dose chemotherapy, papers reporting combined analyses of two or more trials, and companion studies on correlative biology or prognostic factors. PPS was calculated as median OS minus median PFS/TTP for each trial arm. The proportion of OS accounted for by PPS (PPS%OS) was calculated as 100 - [median PFS/TTP/median OS]% for each trial arm.Results: The search yielded 75 trials enrolling a total of 28,973 evaluable patients in 159 trial arms. The following table displays the results, considering trial arms with available medians for both PFS/TTP and OS. PPS%OS is larger in hormone-therapy trials than in chemotherapy trials (P<0.01). Overall, PPS has a stronger correlation with OS than do PFS/TTP (R-squares of 0.83 and 0.24, respectively; both P<0.01), at least in part because PPS is longer than PFS/TTP.Main results Mean ofmedians(months) Trial typeN armsPFS/TTPOSPPSMedian PPS%OSOVERALL1276.920.513.665.7%1. Chemotherapy96718.311.463.7%1.1 Chemo 1st line only597.820.712.964.4%1.2 Chemo 2nd line only146.715.28.559.8%1.3 Other (mixed lines)235.014.19.164.4%2. Hormone therapy296.927.420.574.4%2.1 Hormone 1st line only139.331.121.869.0%2.2 Hormone 2nd line only135.023.218.177.9% Conclusion: The contemporary average median OS in ABC is 20.7 months for first-line chemotherapy ± targeted agents and 31.1 months for first-line hormone therapy ± chemotherapy trials. Subsequent lines of therapy play a major role in determining OS in ABC, and further studies are needed to understand the role of PFS/TTP versus PPS in determining OS, since first-line PFS/TTP have not been convincingly shown to be good surrogates for OS in the literature on ABC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5116.