Background: In the RECIST diagnostic criteria, the concepts of progression by pre-existing disease (PPL) and progression by new metastases (PNM) have been proposed to distinguish between the progression types of cancer refractory to treatment. According to the tumor biology of cancer progression forms, the "PPL" form indicates invasion and the "PNM" form indicates metastasis. On the other hand, recent studies have focused on the clinical importance of inflammatory markers as indicators of the systemic tumor immune response. In particular, absolute lymphocyte counts (ALC) is an indicator of the host’s immune response. Thus, we developed a new measure that combined progression form with ALC. In this study, we clinically validated the combined assessment of progression form and ALC in eribulin chemotherapy.
Methods: From August 2011 to April 2019, a total of 486 patients with locally advanced or metastatic breast cancer (MBC) underwent treatment. In this study, only 88 patients who underwent chemotherapy using eribulin were included. The antitumor effect was evaluated based on the RECIST criteria, version 1.1. To measure ALC, peripheral blood samples collected before eribulin treatment were used. The cut-off value for ALC in this study was 1,500 /μL, based on previous studies.
Results: The PPL group (71 patients, 80.7%) had significantly longer PFS (p=0.022, log-rank) and OS (p<0.001, log-rank) than the PNM group (17 patients,19.3%). In the 51 patients with ALC <1500/μl, the PPL group had a significantly better prognosis than the PNM group (PFS: p=0.035, OS: p<0.001, log-rank, respectively). On the other hand, in the 37 patients with ALC≥1500/μl, the PPL group had a better OS compared to the PNM group (p=0.055, log-rank), but there was no significant difference in PFS between the two groups (p=0.541, log-rank). Furthermore, multivariate analysis that validated the effect of OS showed that high ORR and “high-ALC and PPL” were factors for a good prognosis (p<0.001, HR=0.321) (p=0.036, HR=0.290).
Conclusions: In breast cancer patients with eribulin chemotherapy, good systemic immune status, such as ALC≥1500/μl, was associated with less progression, particularly metastasis, and better prognosis. Furthermore, the biomarker "high-ALC and PPL" was particularly useful as a prognostic marker following eribulin chemotherapy.